20th Annual Scientific Meeting Abstracts

20th Annual Scientific Meeting Abstracts

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS A1 • INDICA1ES ORAL PRESENTATION AT THE JOINT ASN-NKF FREE COMMUNICATIONS SESSION • INDICA1ES PRESENTATION ...

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20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

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• INDICA1ES ORAL PRESENTATION AT THE JOINT ASN-NKF FREE COMMUNICATIONS SESSION • INDICA1ES PRESENTATION AT NKF POS1ER SESSION

o

INDICA1ES PRESENTATION AT THE ASN-NKF JOINT POS1ER SESSION

GROWTH IN IDENTICAL TWINS DISCORDANT FOR UREMIA. Carolyn Abitbol, Gaston Zilleruelo, Brenda Montane, and Jose Strauss . Univ . of Miami, Dept . of Pediatrics, Miami, Florida . Children with congenital uremia often have more severe short stature despite normal growth rates in later life . It has been assumed that their major height deficit is incurred during the first year of life although adequate comparative data on growth i n uremi c infants is not available . The birth of monozygotic twin girls discordant only for one (Twin A) with renal dysplasia allowed ob s ervation and compari s on of their growth during the first 2 yea r s of life. Renal function in Twin A varied from 38 ml/min/1.73m2 at 3 months of age to 30 ml/min/l.73m2 at 2 years of age with serum creatinines- of 0.8 mg./dl and 1.6 mg./dl, respectively. Twin B had normal renal function and anatomy. Body measurements we re taken by a single observer trained in anthropometry. Body mass index (BMI) was calculated as follows: Weight (kg)/Length (m 2 ) . All measurements were expressed as a standard deviation score (SDS) or z score from tables of the normal population published by the National Center for Health Statistics . Body measurements of the twins were similar at birth. At 6 months, Twin A had a weight velocity and BMI -6 SDS below that of Twin B; although her weight and height were at the 50th percentile for the population. At 12 months, length velocity for Twin A had fallen to -2.5 SDS below her he twin. A discrepancy in length of -1 50S was not apparent until 2 years of age . Loss in weight velocity and BMI occurred at 6 months pre c eding the fall in linear growth velocity at 12 months; whereas, loss in length was not apparent until 2 years of age . These observations suggest that monitoring weight velocity and BMI may allow earlier recognition of growth failure in uremic infants .

USE OF SODIUM (NA+) MODELING IN PATIENTS TREATED WITH HIGH FLUX (HF) HEMODIALYSIS (HD) Serllio Acchiardo and Annette Hayden~ Univ. ofTennessee, Dept. of Medicine-Nephrology, Memphis, Tennessee. It has been hypothesized that elevated Na+ concentration during dialysis is responsible for vascular stability. In order to test this hypothesis we studied 38 HD pts being treated with High Aux dialysis. During a 2 m period, . the pts were on no Na+ modeling (basal), 9% (150 mEq/L Na+) linear, 9% step drop and 9% exponential drop . The Na+ program was changed weekly at random without the pts knowledge. No of HD BWt Vol.UF(L) %BWt A %Hypot. %Cramps 228 74.4 3.7 5 20.7 19 226 76.3 3.8 5 9.0* 9* 228 74.5 4.0 5.4 12.0* 10* 224 74.8 3.9 5.3 10.0* 11 * P < 0.001 The main changes in BWt occurred at the beginning of the week. Five pts were responsible for 70% of the episodes of cramps and 7 pts for 75% of the hypotensive episodes. The use of Na+ modeling in pts treated with HF dialysis decreased significantly the hypotension and cramp episodes independently of the type of program used. We strongly advise the use of Na+ modeling for pts being treated with HF hemodialysis.



LONG-TERM RESULTS AFTER CORTICOSTEROID WITHDRAWAL IN PRIMARY CADAVERIC KIDNEY TRANSPLANT RECIPIENTS. Marwan S_ Aboul joud*. Warren !Cupin·, I(.K. Venkat*, Martin Mozes·.

Henry Ford Hospital,

Division of Nephrology and Transplant Surgery, Detroit, MI Prolonged steroid therapy in transplant patients (pts) is associated with significant IOOrbidity. We previously reported the short - te.... results of c"",,lete steroid withdrawal (SW) in 25 primary cadaveric kidney transplant recipients (UR) who were subsequently .. intained on cyclosporine (CSA) and azath i oprine (AZA). (TRANSPLANTATION 54:53-55, 1988). we now report our long-te .... results (follow-up 42:!:14 months[mI) in a larger group of pts using the same protocol. Fifty-two consecutive primary KTR with stable serun creatinine (Cr) <2.0 Rlg/dl with fewer than two rejection episodes while on steroids, and no rejection in the 2 m preceding 51/ were included in the study. SW was initiated from a maintenance dose of methylprednisolone (MP) of 10 RIg qd or 20 mg qed starting 8.8:!:3.8 m posttransplant and completed over 5.1:!:2_2 m. Results: Two patients (Gr-1) had rejection before SW was completed requiring return to 10 1119 qd of MP. One of these returned to dialysis secondary to chronic rejection 24 m posttransplant. The other has a stable Cr of 1.8 mg/dl 9 m later. Fifty pts completed SW without rejection. Thirty-six (Gr-2) of these 50 pts have r .... ined off MP for 28. 4:!:20 "' with no rejection. In Gr-2:the current Cr (1.6:!:.4 ma/dl) is not significantly different from the pre SV value (1.4:!:. 4 RIgId!); current serun cholesterol (215:!:47 vs 250:!:47 mg/dl), mean arterial BP ~97:!:9 rmlHg vs 102:!:10 rmlHg) and WBC count (5.4:!:1.9 vs 7.5:!:2.4 K/rmt' are Significantly lower (p<0.05) than pre SII values. Fourteen pts (Gr-3) required reinstitution of MP, few days to 33 m after completion of SII, because of rejection (12 pts), adrenal insufficiency (1 pt) and leucopenia (1 pt). Two of these 14 pts had graft failure 44 and 56 m posttransplant due to chronic rejection and chronic rejection + recurrent diabetic nephropathy respectively. The current Cr of the remaining 12 Gr-3 pts is 2_2:!:_4 mg/dl. In conclusion, sw can be safely achieved and maintained in the majority of carefully selected primary cadaveric KTR receiving CSA and AZA. SW results in significant iq>rovement in BP and senD cholesterol. However, rejection My occur long after SW and reinstitution of steroids may not result in c"",,lete restoration of renal function.

• CERVICAL SPINE DISEASE (CSD) IN DIALYSIS PATIENTS. R. Durwood Almkuist, William P. Nixon, John M. Herion, Robert A. Moore, Wilmington, N.C. Vertebral manifestations of renal osteodystrophy include compression fractures, the sclerotic changes of the "rugger jersey" spine and the recently described erosive spondyloarthropathy (ESA). Only ESA has shown a predilection for affecting the cervical spine. Over a 9 year period at a free standing outpatient dialysis unit, we have seen 15 patients with signs and symptoms of CSD. Three cases immediately followed trauma; the others presented as headache, neck, shoulder and/or arm pain. Eleven of the 15 were 60 years old or older. There were 12 males and 3 females; 13 blacks and 2 whites. One patient was on CAPD, the rest on hemodialysis. The average time on dialysis was 48 months. No patient was hypercalcemic but most had evidence of hyperparathyroidism. Three had evidence of ESA; the remainder had fractures or degenerative changes. Three patients required cervical laminectomies and fusions; two required external fixation; the others were treated with soft collars, calcium and Vitamin D preparations. During the same period none of our other dialysis patients required lumbar disc surgery. Our experience suggests that dialysis patients are at risk for developing CSD, that CSD can cause significant morbidity and that the etiology may be multifactorial.

American Journal of Kidney Diseases, Vol XVII, No 2 (February), 1991 : p 247

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20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

CALCIPHYLAXIS: AN UNDERDIAGNOSED SYNDROME IN END STAGE RENAL DISEASE. Amerling R, Spinowitz BS, Malluche HH, Chary tan C. Beth Israel Medical Center, N. Y. Calciphylaxis is a devastating, progressive ulcerating syndrome occurring in ESRD patients who have diffuse medial arterial calcification. Five patients are described from a dialysis population of approximately 350 who were diagnosed with calciphylaxis over an 18-month period. All presented with painful, peripheral ischemic ulcerations of the upper and lower extremities. One patient also had a penile ulcer. Diffuse calcification of the tun; ca medi a of medi urn and sma II arter i es was demonstrated both radiographically and histologically in all pati ents. The average serum calci urn, phosphorous and alkaline phosphatase were 9.8mgX (range 9.0-10.6), 6.4mgX (range 4.7-9.1) and 355 lUlL (range 108-983; normal: 26-88), respectively. The average hematocrit was high for our uni t (pre-eryth ropoi et i n) at 32% (range 28-40). 3/5 pat i ents underwent revascular i zat i on procedures (2 angioplasties, 1 bypass graft) with poor cl inical results. 3/5 patients had subtotal parathyroidectomy, with significant improvement in only 1/3. In the two who did not improve, significant aluminum toxicity was found at bone biopsy. Multiple amputations were required in 4/5 patients. All followed a relentless course with 4/5 patients expiring within 3-36 months from initial presentation. Calciphylaxis seems to be more prevalent in the ESRD popUlation than has been recognized. Its clinical expression may be facilitated by a non-anemic state. The widespread use of calcium, calcitriol and erythropoietin may lead to an increased incidence of this syndrome.

BLOOD RllEOLOGIC OBSERVATIONS IN RENAL TRANSPLANT PATIENTS J.Barbas, L.Cardoso, P.Yolanda, C.Saldanha, and J.Martins e Silva. Nephrology Unit Hosp. Sta.Maria, and Institute of Biochemistry, Fac. Medicine, Lisbon, Portugal. The purpose of this study was the evaluation of some haemorheological parameters (plasma viscosity, erythrocyte aggregation, erythrocyte filterability) and biochemical data (protein and lipid profiles of erythrocyte membranes) from a group of renal transplant recipients (TxR), compared with a control group. The patients had significant increased (p.¢.OOl) plasma viscosity (PV) and erythrocyte aggregation (EA)(p
[] SUBCUTANEOUS (SQ) ERYTHROPOIETIN (EPO) INCREASES HEMATOCRIT WITTHOUT INDUCING HYPERTENSION IN HEMODIALYSIS (HD) PATIENTS. RC Atkinson,* Q Jones,* KA Kirchner,* M Elnour,A D Butkus and J Bower. Univ. of Mississippi Med. Ctr., and Kidney Care Inc., Jackson, MS. EPO is a significant advancement in the management of anemia in ESRD. However, its full potential has been limted by cost, need for intravenous administration and side effects such as hypertension, seizures and clotting of vascular access. EPO has a longer half life when given SQ. If SQ EPO increases hematocrit then SQ EPO may allow a reduction in dose and in side effects as well. 101 patients on chronic HD in a limited care facility were given SQ EPO at 30 units/kg ideal body wt after each dialysis. Patients were eligible for study i f their hematocrit (HCT) was <25%, iron stores were normal, and pre EPO diastolic blood pressure was <100 mmHg. Mean HCT was 21.5~4.8% (mean ~SD) prior to EPO and increased (p<.05) to 26.2+5.7% following 1 month of SQ EPO. Mean HCT contTnued to increase with time and in 12 patients on SQ EPO for 6 months mean HCT was 28.3+4.5% (p<.05 vs baseline and 1 month). Mean dose of EPO at 1 month was 1825 units and at 6 months was 1709 units (p=NS). Mean systolic and diastolic blood pressure did not change during treatment. SQ administration was well tolerated by all patients. There was no increase in frequency of vascular access complications, seizures, or hyperkalemia. Thus, low dose SQ EPO is effective in raising and maintaining the HCT in chronic HD patients and is associated with a low incidence of hypertension or other complications.

[] PRURITUS ASSOCIATED WITH ACETATE (Acet) HEMODIALYSIS (HD). RH Barth and GM Berlyne. VA Medical Center and SUNY. Brooklyn NY. Pruritus is a distressing and common symptom associated with HD. We studied the difference in Incidence of symptoms between HD with Acet and bicarbonate (Bic) dialysate. Ei~ht patients (pts) were dialyzed for one month using "high-flux· 1.7 m polyacrylonitrile hollow fiber dialyzers (Hospal Filtral16 R) for 3 hr at 550-600 mljmin biood flow rate. Acet- (42 mEq/l) and Bic- (38.5 mEq/l) containing dialysate was used during alternate weeks in a randoml2ed crossover pattern. Blood was sampled before and after each HD; dialyzer clearance and KtjV (urea) were determined by direct quantification of dialysate urea for each pt once on each dialysate. Serum Acet levels were measured at t=O. 1.5. and 3 hr. Two pts had frequent severe episodes of pruritus during Acet HD but not during Blc HD. PRURITIC PTS (2) NON-PRURITIC PIS (6) Acet HD Bic HD Acet HD Bic HD Dialyses (n) 13 13 46 33 Pruritus (n) 8 0 1 1 Syst BP<100 (n) 4 1 38 15 Vomiting (n) 0 0 15 0 Serum Acet (mEq/I): t=O hr .42 ± .49 .19 ± .07 .29 ± .37 .17 ± .08 t;1.5 hr 2.99 ± .34 .43 ± .11 4.42 ± 1.27 .41 ± .14 t;3 hr 2.91 ± .45 .68 ± .33 4.52 ± 1.85 .63 ± .25 Phos (mg/dl): t;O hr 7.0 ± 1.8 6.4 ± 1.6 5.7 ± 2.1 5.7 ± 2.3 t;3 3.7 ± 1.0 3.4 ± 1.4 2.8 ± 0.8 3.0 ± 0.9 Pts with Acet-associated pruritus were not different from the rest of the group with respect to BUN. serum creatinine. alkaline phosphatase. calcium. pH. delivered urea clearance or KtjV. They had fewer episodes of other Acet-related symptoms. such as hypotension. nausea and vomiting. In the pruritic pts peak serum Acet levels were lower (P<0.01). pre-HD serum phosphorus was higher (P<0.05). and serum PTH (immunoradiometric assay for intact molecule) was within the normal range (9.0 and 14.4 pmoljl). We conclude that there exists a group of pts with a sensitivity to Acet which is manifested primarily by pruritus. A trial of Bic HD is warranted for pts with intractable intradialytic pruritus.

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20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS •

INCRFlISED

KIDNEY

ACXlJ!olJIATICN

(f'

o.1-MIarolillJLIN

IN

UNINEPHREt'IOOZED RATS

C. Bianchi*, C. Iklnadio*, G. Traroonti*, C. Vannucci*, A. casani*, V. Ricchiuti*, P. lDrusso*, P. Giannotti**, M. Cecchi**, C. Bonino***, E. Seccamani***, F. llmghi***. *Unita di Nefrologia, Clinica Medica 2, University of Pisa; **Clinica Urologica 2, University of Pisa; ***SORIN Bianedica, Saluggia VC, Italy In normal an:iJllil.ls llillIY l(Jlo{ rm; proteins, such as 0.1microglobulin (0.1-1'1), are highly aCCllllllated by the kidney and their urinary excretion is generally l(Jlo{. To verify if the reduction of renal mass can lOOdify this behavior, kidney uptake and urinary excretioo of hlll\an labelled 0.1-1'1 have been determined in uninephrectanized rats (\]NI). The eJ..-perirents have been carried out in 22 Sprague Dawley male rats (26o-400g). Eleven animals underwent right nephrectany. Two weeks after surgeIj', UNI and an equal nllIlber of control rats (C) have been injected with a bolus of 0.1-1'1 labelled with I -131 and sacrificed 18 min after the injection (kidney peak time of 0.1-1'1 in normal rats). Radioactivity of plasma, left kidney and urine was measured . The results (percent of injected dose, mean±.SD *p
Plasma (1g) Left kidney (total) Left kidney (1g) Urine (total)

UNI 2.66±9.25** 29.48+3.08** 19.80+2. 31* 6.14~2.29*

C 1.~.27

19. 76!.2. 13 17 . 31!.2. 23 4. 32!.1.52

Conclusions - In UNI, plasma retention, kidney acClllli.llatioo (total and per gram) and urinaIj' excretioo of 0.1-1'1 are higher than in C. After unilateral nephrect~ the increase of aCClmllatioo of o.1-M (and probably of other l(Jlo{ rm; proteins with the sarre behavior) in the rennant kidney could play a role in the progression of kidney injUIj' .

ANTI-LYMPHOCYTE SERUM (ALS) IN RENAL RECIPIENTS WITH DELAYED GRAFT FUNCTION (DGF). PA Bowen, JJ Wynn, K. Johnson, C Kelly, K. Ferrara and AL Humphries. Departments of Surgery and Medicine, Medical College of Georgia, Augusta, GA and Vanderbilt University Medical Center, Nashville, TN. ALS was given to patients (P) with DGF to avoid combined ischemic and CS toxicities. CS was delayed 24-48 hrs in P with early function (EF). CS was given to DGF P when function improved for 2-3 d. All P received prednisone 30mg/d and azathioprine 2.5mg/kg/d. 70 cadaver donor p were studied, 47 male, 36 black and 34 white, 15 (21%) diabetic. Results: 35 (50%) P had DGF. 9 (26%) had acute rejection (AR); 6/9 (66%) reversed with methylprednisone (MP), 2 MP failures reversed with OKT3 and 1 (2%) P lost allograft. Of 35 P with EF 21 (60%) had AR. AR reversed with MP in 5, MP plUS ALS or OKT3 in 6 and OKT3 alone in 9. One P lost allograft (2%). SCR was similar at 1 and 6 mo. One year graft survival (GS) was 92% in DGF and 94% in EF P. Minor infections (1) occured more in DGF P while serious 1 was seen in P with AR regardless of DGF vs. EF. We conclude:l) ALS reduces risk of AR in DGF P with excellent GS 2) delayed CS and low dose prednisone increases AR but has no long-term effect on GS 3) DGF had no adverse effect on GS 4) ALS in DGF P increases minor, but not serious 1 and avoids use of CS 5) serious 1 occur after AR therapy irrespective of DGF or EF.

o INCREASED

RATES OF SENSITIZATION AMONG FEMALE RECIPIENTS OF DONOR SPECIFIC TRANSFUSIONS (DST) PRIOR TO RENAL TRANSPLANTATION. Paul Bolin~ Clara H. Danziger: Lynn W. MCCoy~ William F. Finn. Dept. of Medicine, University of North Carolina, Chapel Hill, N.C. The utility of DST has been questioned due to the almost equivalent rates of renal allograft survival when cyclosporin A (CsA) is used without DST compared to the use of azathioprine (Aza) with DST; the risk of sensitization to atypical RBC alloantigens with DST being offset by the risk of CsA nephrotoxicity. We have examined subgroups in an attempt to isolate those in whom the increased risk of DST would be unacceptable. 39 adult patients underwent DST with low dose Aza, 50 mg QD, between 1981 and 1989. Five of 21 female recipients of DST were sensitized compared to 0 of 19 male recipients (p <0.05; Fischer's exact test). 4 of 12 gravid females were sensitized compared to 1 of 9 non-gravid females. Further analysis revealed that 3 of the 5 female recipients with offspring as donors were sensitized, compared to 0 of 3 male recipients from offspring. These data indicate that female recipients of DST have an increased risk of sensitization which may be related to prior pregnancy. DST should be reserved for subgroups with a low risk of sensitization.

o A RAPID METIIOD FOR ESTIMATING KTN AND PCR:

TIlE 60/40 RULE. James C. Brandes* and Eric P. Cohen* . Med. Coll. of WI, Dept. of Med., Milwaukee, WI. (intr. by Walter F. Piering). Computer-assisted calculation of Kt/V and PCR involves several timed blood and urine collections. In order to develop simpler methods of rapidly estimating Kt/V and PCR, we measured urea kinetics of 180 dialysis sessions in 113 hemodialysis patients on thrice weekly dialysis. KIN and PCR were calculated according to Sargent and Gotch. As expected from the exponential decay inherent in KIN (Basile, AIKD 15:40, 1989), it directly correlated with percent reduction of urea (PRU): PRU=[(preBUN-postBUN)/preBUN] x 100, and Kt/V=(0.033xPRU)-0.86, r=0.88. PCR (grn/kg/day), a nonexponential linear phenomenon, correlated with the absolute rise of the week's first post-dialysis BUN to the mid-week predialysis BUN (dBUN): PCR =0.32+(0.02xdBUN), r=0.86. This correlation was still significant for those patients with residual urine output (r=0.83, N=45).

r----------,

2

2 II:

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11.1

~1

50

60 PRU

70

80

0L..-..L...-...L.......L......1...--L--L--I 10 20 30 4050 60 70 80 <1 BUN

In conclusion, these two equations can be used to quickly and accurately estimate KtN and PCR at the patient's bedside. Clearly, a patient with a PRU~60% and a dBUN~40 mg/eIL is estimated to have a Kt/V~l and a PCR ~l gm/kg/day.

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20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS PERCUTANEOUS RENAL BIOPSY WITH THE USE OF REALTIME ULTRASOUND. David M. Burstein" Melvin M. Schwartz and Stephen M. Korbet. Rush M"edical College, Dept. of Medicine & Pathology, Chicago, Illinois. We describe our experience in a teaching institution with real-time ultrasound as a localization and guidance tool for percutaneous renal biopsy. Two hundred biopsies performed between June 1983 and Jan. 1990 were reviewed retrospectively. Nephrology fellows performed 83.5% of the biopsies. The average age of the pts was 43 ± 17 yrs (range 6-80) and renal insufficiency (SCr~1.3 mg%) was present in approximately 60% of pts biopsied. The primary indications for biopsy were to evaluate for proteinuria (46.5%) and the renal manifestation of systemic lupus erythematosus (24%). Material for light microscopy, immunofluorescence, and electron microscopy was obtained in 99.5%, 95.0%, and 98.0% of cases respectively. Adequate tissue for diagnosis was obtained in 97.5% of pts. The primary diagnosis was glomerulonephritis in 77.9% of cases. Complications (gross hematuria 12, hematoma 7, both 5, A-V malformation 2) were observed in 13.7% of pts with 8.1 % of these minor complications and 5.6% major complications which required blood transfusions. Bleeding complications requiring massive blood transfusion and/or therapeutic radiologic intervention were seen in 1.5% of patients. No significant difference in age, serum creatinine, or coagulation parameters between patients with or without complications due to percutaneous renal biopsy were noted. We conclude that real-time ultrasound is a safe, accurate method in localizing the kidney for percutaneous renal biopsy. However, patients must still be observed carefully post biopsy for potential complications.

.. SIGNIFICANT INCREASES IN SERUM ALUMINUM (AI) LEVELS DURING SUCRALFATE (SCFT) THERAPY IN PATIENTS WITH CHRONIC RENAL DISEASE (CRF) DESPITE INCREASED RENAL Al CLEARANCE (Cl). E. Burgess, D. Muruve*, University of Calgary, Calgary, Canada In order to assess Al absorption from SCFT, 6 patients CRF (Clcreat 0.2-0.9 mIls) received SCFT 1 Gm 4x/day on Days 1-21. Serum and urine (serum only) were collected on Baseline x2, and Days 2, (3,4),8,15,22,(23,24),29 and 36. Samples were assayed by graphite furnace atomic absorption spectrometry. Serum Al levels (SAl)(umol/L) increased by Day 2, remained elevated to Day 24. Urinary Al excretion (UAl)(umol/D) remained increased throughout. Renal Cl Al (mIls) rose during SCFT, but returned to baseline by Day 36 (Day 15 vs Day 36 p=0.003), and fractional excretion of Al (FE AI) was significantly higher on Day 15 vs Day 36 (0.26±0.9 vs 0.11±0.02, p=0.007). Base Day8 15 22 29 P 0.25 0.008 0.10 0.88 0.85 0.82 S AL 1.5 0.001 0.4 5.1 6.5 5.1 U AL The attenuated rise in SAl may have been due to distribution to a peripheral compartment, and this would also explain the biexponential elimination curve. The increase in renal CI Al with increased serum Al levels may be secondary to higher ultrafiltrable Al at higher SAl levels and contributed to the attenuated rise in SAl levels. Despite increases in renal Al excretion, significant elevation of serum Al levels occurred with therapeutic doses of SCFT. Long courses of SCFT should be used with caution or avoided in CRF.

.. RENAL CADAVERIC ALLOGRAFT SURVIVAL IN BLACKS IS THERE STILL A DIFFERENCE? Donald E. Butkus. Dept. of Medicine, Univ. of Mississippi Med. Ctr.,Jackson, MS. Renal allograft survival in blacks (B) has been reported to be significantly less than in caucasians (C), especially in multicenter and registry data containing patients treated with variable immunosuppression. We and others have previously reported that the poor primary cadaveric allograft survival at 1 year in blacks with conventional immunosuppression (P+Az) was improved with ATG and nearly abolished by cyclosporin (CSA). To evaluate the effect of immunosuppression on graft survival in blacks we analyzed 16 single center studies which reported on primary renal cadaveric transplants (n=4553) and catagorized data on race and immunosuppression: (l-yr graft survival) C(n) B(n) C(%) B(%) P+Az ~ Z35 66.2 46.2 P+Az-lATG 1146 152 73 56. P+AziC.9\ 1191 762 76.3 70.3 P+Az-tC5l\iATG 1144 l!3 8!1.5 82.6 Anograft survival in both (B) and (C) incrementally improved, and racial differences narrowed, with addition of ATG to P-Az, and with introduction of CSA. Addition of ATG to CSA improved graft survival further and abrogated the difference in graft survival between (B) and

(C) •

Differences in I-year allograft survival between blacks and caucasians may be overcome by sequential immunosuppression suggesting a role for differences in immunologic responsiveness rather than compliance or socioeconomic factors. Randomized studies are needed to substantiate these findings.

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INFLUENCE OF RACE ON RENAL ALLOGRAFT OUTCOME. J. Butle!, S. Korb, J.A. Light~ A. Aquino, J. Jonssoff, N. Khawand, A. Ali, C. CUrrier, J. Romolo and J. Gonzalez. Transplantation Services, The washington Hospital Center, Washington, D.C. A higher incidence of end-stage renal disease occurs in the American Black population with respect to other racial ~roups, however, renal transplant therapy ~n this population has produced less favorable results when compared to nonBlacks. In the present study we report our experience in renal allo~raft outcome of Black and Caucasian recip~ents. Data accumulated on transplants performed over a 5 year period, (1/85-12/89), was analyzed for racial influences on transplant outcomes. The study groups consisted of 206 Blacks (B) and 231 Caucasians (C). The variables assessed included Sex, Age, Cold ischemia, Per cent reactive antibody, Hospital stay, Transplant type and number, Rejection episodes, Delayed function and HLA match. The influence of donor/recipient racial dis~arity was also evaluated. All pat~ents received CyA, Azathioprine and steroids along with peri-operative cytoreductive thera~y with either MAG or OKTJ. The cummulat~ve graft and patient survival for each group was B-80.1% and 94.2% and C-82.2% and 95.7% respectively. None of the variables assessed were statistically significant. Excellent renal allograft results may be obtained regardless of race with a detailed pretransplant evaluation, aggressive peri and post operative immunosuppressive managment and a positive tracking outpatient follow-up system.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS IS DEFEROXAMINE (DFO) INFUSION TEST STILL USEFUL IN HEMODIALYSIS PATIENTS? Gerard CAM*, Pierre SIMON*, Kim S ANG*, Yves MAURAS**, Pierre ALLAIN**. Dept of Nephrology* La Beauchee Hospital St Brieuc 22000 and Lab of Pharmacology** CHU Angers 49000 France. Since 1982, 556 DFO tests were performed in 78 pts on hemodialysis according to method described in a previous paper (Nouv. Presse Med. 1982 : II : 209). Test was performed twice each year in all pts in order to evaluate tissue aluminium (AI) stores and to distinguish patients with and without AI-related osteodystrophy. In our unit, program for preventing AI intoxication was rigorously applied : dialysate AI concentration <: 10 Ilg/I, AI gels replaced by calcium carbonate, control of AI-containing food intake. Indications for bone biopsy were basal serum AI 50 Ilg/l and an increment in serum AI concentrations of greater than 150 Ilg/1 (~ AI) after DFO test. Thus in 1982, 34% of patients had positive DFO test. This incidence decreased slowly during the period under review: 21.5% in 1984, 10% in 1986, 7.5% in 1989. Bone biopsy was performed in 35 pts and a close relationship was found between A AI or basal serum Al and bone AI. Before 1987, 6 pts were treated by DFO for 6-10 months, after 1987 one only pt was treated. We conclude that 1) DFO test was useful to detect mild AI-related osteodystrophy 2) application of a program for preventing Al intoxication is effective on the incidence of positive DFO test 3) Therefore the use of DFO test to do diagnosis of Al intoxication is now limited to some patients who still are strongly exposed at risk.

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CaH- - INlUlID r.mJLATI
Alberto CantallWi*B, Marc Salit'B, Urberto Valente*§. Nephrol. Unit, St.Paul's Hasp. Savala, Italy; Baxter,Ramd Laf'K:). \\hich also have been sho.m to have specific receptors for 1,25 (rn)2 03. To further stllqy this prcblem we evaluated in 10 polycytilemic kic:hey transplant patients (PK'IP) :in vitro:a) erythroid colo\y(JlIiU-E and CFU-E)gro.Jth fran ~ in the presence of increasing 00ses of exogm:::os Ero b)13FU-E and CFU-E develqrnent in the presence of increasing d0ses of CaH- alme,CaH- plus 1,25(


AS

CY~ POI'ENfIATI
Alberto CantallWi*B,Marc Salit'B, lkIi:leF"v:> Valente*§ • Nephrol. Unit, St.Paul's Hasp.Savcna,Italy; Baxter, Ramd Lake, Ill.USAB; Surgery Transp. Unit, St.Martin Hasp. Genova, ltaly§. It has been sho.m that increased cytcplasmic CaH- is me of the first sig;'1s of perip1eral blcod T-IYJTlixx:yte (PBI'L) arxI m:nxyte (1m) activatien lea:ling to cytckine release,and that this can be irtribited by calciun antagcnists. We have previrusly sho.m that in K'Il' withrut acute rejectirn treated with Cyclasporine-A (CyA), PBI'L and PIl\I CaH- is siglificantly lCMer than with acute rejectien or in healthy centrols, and that these cells produce srraller ffiOJJ1ts of the cytckines Interleukin-2 (IL-2) ,garma-Interferrn (garma-IFN) ,InterleUE2 and LTB4; 2. plasma creatinine; 3. rurber of acute rejecticn episodes/patient/year. Results were carpared with 10 K'Il' rot tadng the a calciun eot:ag:rllst. Results: in vitro a'Xl in vivo Diltiazem crused a ~t reductien in PBI'L a'Xl PIIoI cytcplasmic CaH- levels a1d cytckine procilctien, significantly decreased the average CyA cbse/patient/year and was acCOTpanied by reduced plasm creatinine levels. HCMever, there was ro siglificant change in the rwber of acute rejectirn episodes/patient/year. These results indicate that Diltiazem is able to potentiate the effect of CyA in K'Il', th.ls allCMing a reciJctien of its cbsage and, therefore, of Its side effects •

FLUCONAZOLE TREATMENT OF CRYPTOCOCCAL MENINGITIS IN CYCLOSPORINE TREATED RENAL TRANSPLANT PATIENTS. Ralph J. Caruana, P. Allen Bowen, James J. Wynn, and Laura L. Mulloy. Medical College of GA, Augusta, GA. Renal transplant patients treated with cyclosporine are at increased risk for the development of cryptococcal meningitis and may have an increased risk of amphotericin-B nephrotoxiCity and flucytosine marrow toxicity. We treated two renal transplant patients with cryptococcal meningitis with fluconazole after short induction courses of amphotericin-B (198 and 610 mg) and flucytosine led to severe declines in renal function (tripling of serum creatinine) and leukopenia (WBC < 3000). Fluconazole at a dose of 100 mg/day was well tolerated by the two patients. Serum creatinine levels and WBC returned toward baseline. CSF cultures became negative for cryptococcus, and cryptococcal antigen titres in blood and CSF fell progressively . Cyclosporine levels rose and significant dosage reductions were necessary. The patients are asymptomatic after having been continued on maintenance fluconazole (100 + 200 mg/day) for 3 months. Fluconazole may be an attractive alternative to amphotericin-B and flucytosine for treatment of cryptococcal meningitis in cyclosporine treated renal transplant recipients.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

A6

ttEFFICACY OF EPOETIN THERAPY USING DOSES DICTATED BY HCFA REIMBURSEMENT. Marilani S. Ching·Hansen * (intro by Richard Drake). Good Samaritan Hosp, Pharmacy· IV Dept, Portland, Oregon. Ideally, doses of epoetin (recombinant human erythro· poietin) are based on patient size, symptoms, baseline hematocrit and response in correction of anemia. However, doses of epoetin are limited to avoid financial deficits. The epoetin dose and response of 100 patients were reviewed from outpatient dialysis unit charts. Prescribed

doses of epoetin were limited to 4000u

TI~

maximum and in downward 500u increments due to

pharmacy predrawn syringe program to reduce drug waste. Of 100 patients, the average dose per kilogram patient weight was 52.5 (range 14.9· 104.5), the average pre·epoetin Hct was 27.1% (19.1-39),

however these Hct

reflect androgen

and/or transfusion therapy. 10 patients showed no significant improvement, 3 of which still required transfusio.ns and the other 7 with an

already high Hct ave of 31.3%. Responding patients defined as ' 6X Hct required an average of 39 (5·172) days. 80X of responding patients reached goal(30·33X) with the '6X Hct, remaining 20X required an average of 48 (9·95) days. 43X required some transfusions since epoetin initiation although the dialysis units report an overall decrease of 75X in transfusion use. As an aside, 36X required parenteral iron supple· ments. In conclusion, successful correction of anemia with epoetin can be accomplished under HCFA reimbursements, however dosing still requires individualization and reimbursement should be individualized as well.

IMMEDIATE AND LONG TERM PROGNOSIS IN ACUTE RENAL FAILURE (ARF) IN THE ELDERLY Jacques CLEDES and Armelle Gentric - Univ of Med - Dept of Nephrology and Internal Medecine - Brest - France The incidence of ARF increases with age. A few studies have reviewed immediate prognosis of ARF in older patients, but, no results do allow any conclusion on long term renal prognosis. 'ur retrospective study included 46 patients over 70 years, referred to our renal unit between 1983 and 1989. Survivors were followed-up 6 to 71 months after discharge (mean: 39 months). The evolution of renal function was evaluated by measurement of serum creatinine. Data analysis employed X2 with Yates correction, Student-t and ~ann Whitney tests to compare survivors and deceased and ~o compare patients with normal and abnormal renal function at discharge. During hospitalisation, 11 patients (23,91%) died. Our univariate analysis reveals that 3 variables indepedently influence mortality : consciousness disturbance (p<0,001), high urea concentration (p<0,01) and hypoalbuminemia (P<·O,001). Age doesn't affect adversely the prognosis. The mean follow-up of the 35 survivors was 39 months 15 patients (42,86%) had a complete functional recovery, 8 (22,86%) had incomplete recovery and 2 (5,71%) were on chronic hemodialysis. These results are similar to those observed in a younger population. In conclusion we believe that age alone should not be used to predict the immediate survival and the long term renal outcome in ARF in thE elderly.

tt THE RELATIONSHIP BETWEEN BLOOD PRESSURE AND ALBUMINURIA IN PATIENTS WITH TYPE I DIABETES MELLITUS. A.M. Chonko, W.V. Moore*, M.L. MacDougall, LB. Wiegmann, Univ. of Kansas Med. Ctr., Kansas City, KS. Increased blood pressure may be an important mediator in the development of diabetic nephropathy which may be indicated by the presence of increased albumin excretion rates (AER). We therefore examined prospectively an outpatient population (N=166) of patients with type I diabetes whose mix reflected the community (53% male, 47% female, 86% caucasian, 12% black, 2% hispanic). Hypertension was defined as treatment with antihy·pertensive drug and by repeated sphygmo-manometer reading (sys>135 or dias>85 rnrnHg); AER is given after log transformation. Results (Mean + SE; * = P
. . LYMPHOCYTE POPULATIONS (Ly P) AND IMMUNOGLOBULIN (Ig) LE\~LS IN DIALYSIS PATIENTS (HD Pts) ON rhEPO. F.Collart~ M.Dratwa, F.Mascart~ R.Wens~ Brugmann University Hospital, B~ussels, Belgium. It has been shown 'that rhEPO can influence Ly in vitro. To evaluate the possible in vivo effects of rhEPO on the immune system we studied Ly P identified by monoclonal antibodies [T3(total) , T4(helper), TB(suppressor) , NK(natural killer) cells and B Lyj and IgG, IgM, IgA and anti-HbS antibodies serum levels before and after 6 months on rhEPO in 21 HD pts. Results are given as means ± SEM : NOrmal range Start 6 months P T3 cells 750-2300 B05±35 B2Ot53 NS T4 440-1520 51Q±30 475±47 NS TB 190-920 341±60 347±52 NS T4/TB ratio 1.B1+0.1 1.94±0.19 1.56±0.15(.05 NK cells 75-230 45±39 311±4B -: .01 B cells 25-195 7B±10 53±1B < .02 IgG (mg/dl) 60B-1572 1336±90 1216±1oo NS IgM 56-352 161t25 13B±15 NS IgA 45-336 251±35 196±21 NS Anti HbS (UI/ml) 402±224 265±151 NS In the subgroup of pts with a pre rhEPO T4/TB ratio ~. 2, significant increase in TB cells and decrease in T4 cells were also seen. None of the changes observed was correlated with the changes in Hb, HCT or RBC counts, nor with the changes in iron status, nor with the total dose of rhEPO administered. Thus, 6 months of rhEPO treatment results in a decrease in T4/TB ratio together with an increase in NK cells and a decrease in B LYjserum Ig levels remain unchanged. The mechanism(s) responsible for these changes and their possible clinical significance remain to be determined.

A7

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

o HEMODIALYSIS OF IODINE AS 1311. R. Michael Culpepper, Jerry

I. Hirsch, and Melvin J. Fratkin (intr. by Anton C. Schoolwerth). Med. CoIl. of Virginia, Depts. of Medicine and Radiology, Richmond, Virginia. Although serum iodine (I') levels may be elevated In patients on maintenance hemodialysis, there is little knowledge of the clearance of r using current dialxsis techniques. We measured the hemodialysis clearance of 13 I given as Nal to a patient with metastatic medullary carcinoma of the thyroid who was undergoing maintenance hemodialysis. Clearance was calculated from the AV difference of 131 1 activity and from the appearance of 131 1 in dialysate using single-pass dialysate delivery (500 ml/mln) and a parallel-plate dialyzer (QA 250 ml/min). Activity was measured in whole blood (WB), whole plasma (WP), and a supernate of plasma (PS) washed x3 with 10% TCA. All counts were decay corrected to time zero (administration). 131 The relevant 1 clearances (mean.±. SEM) from blood activities are given in ml/min and period in hrs post.
RIE

(F lELI~

PfIffiI

~

s.*,~

an Dial. lhit, Pad::Iua;*GEn!rnl Itrlicine CaEelve (PaOOva ) Italy. Intr. by Prof. P. :luJchill.i 'lre role of' Ihli.odJa::ter Pylcri (H.p.) infecticn in uranic

G.F •• - NE;t1rolcgy

(HI;:ierrts ramim utiear.

M
~ levels in tile gpstric DEdiun IIE\Y favar ttebaet.erill growth. 'lbJs, uranic patiEnIB in di.aJ3Isis tHJe :in:nlased lUl levels, des'zpi"IE ro evidEn:e of' peptic ulcer.

In crder iD ~ tile role of' H.p. infecticn in uranic patiEnlB, :E patiEnIB en dialysis, 21 nales an 17 famles, nngill?; fran 32 an 00 years, were evaluatEd. As a carIrol gra.p, were tested 88 sera fran blocxl dnlrs (53 nales an 35 famles, ~ ragl 1.8-64). f:Pecific G.M.A. inm.n:gl.dlliin fer H.p. were tested with saniq..aItitative nethod (GAP 'H'Sr BID-RAD). These Ig levels were
Sb.rlmt t

test

an X2

test.

A positive H.p. test

was observed in 27,2% of uremic patients without any difference from healthy subjects. The majority of H.p. positive uremic hal blocxl gra.p A an 0, famles ha:i a bigler dialytic ~ 7.5 versus 3.25 years , P(0.a>. These mm s.mst 1hat H.p. infectien is CCJJpar'le in healttw aiJjects an uranic patiEnIB an, cnly in famles it seam related iD a

/III'e

prolcrgJd dalytic beab'lllt.

tive test is preOOninmt in blocxl gra.p A 1hat (HI;:ierrts of' blocxl gra.p A

an 0

'lre H. p. pooi-

an 0,

~

IIE\Y have partirnl.ar

cosidic :residIes, 1hat allow bacterial growth.

gly-

INCREASES

PROTEINURIA

IN

DIABETIC

MAN. Bryan K. Demarie* and George L. Bakris, Renal Research Division, Ochsner Medical Foundation, New Orleans, LA 70121 Reductions in glomerular capillary pressure (PGC) are associated with amelioration of proteinuria and glomerular injury in diabetic animals. The effects of calcium antagonists on this parameter vary. Therefore, we undertook the present study to examine two different classes of long-acting calcium antagonists, diltiazem (D) and nifedipine (N) which have varying effects on PGC in ten noninsulin dependent diabetic, hypertensive patients with renal insufficiency to test the hypothesis that D attenuates proteinuria and preserves renal function. After baseline data collection, each subject was initially (1) randomized to either N, 30 mg daily or D, 90 mg twice daily, for six weeks followed by a two week washout period and crossover (CO) to the other drug for an additional six weeks. Patients were then followed monthly for a period of two additional months and remained controlled for the duration of study. Mean arterial pressure was equally reduced in both experimental periods. The mean differences in renal parameters were noted: ~ Uprotein V(g/d) A CrCl (ml/min) 1 ~ I ~ D -1.4±O.3*+ -1.3±0.2*+ 3±1 2±2 1.6±0.7* 1.4±0.3* -16±3*+ -13±2*+ N *P<0.05 different from baseline; + different from N. At the end of the study renal function did not improve in the nifedipine group; however which proteinuria decreased by 15%. We conclude that nifedpine adversely affects renal function in diabetic man

o

:IN lIDIC PATIENI'S

Di. I.axJro D., IBttilo G.A., Tessaro P.*,Gkria30

o IHFEDIPIBE

LOW PROTEIN DIET VERSUS A SUPPLEMENTED DIET IN CHRONIC RENAL FAILURE Romagnoli G.F .. Dattilo G.A., Di Landro D. Department of Nephrology and Dialysis, Padova Hospital. Italy. Intr. by Prof. P. Zucchell1.

In order to compare the efficacy of a conventional Low Protein Diet (LPD) versus a Supplemented Diet (SO) in slowing the rate of decline of renal function in chronic renal failure (CRF), the authors evaluated two groups of CRF patients placed on two different dietary protocols. The two groups, including 86 subjects, mean age 48.6+18 years were comparable for age, sex and underly~ng renal disease and exhibited similar plasma creatinine levels (4.5+2.3 LPD and 4.8+2.7 SO). The first group of 43 subjects was stdrlcd on a LPD containing 0.6 gm/kg/day protein, 10 mg/kg/day/phosphate and 35 kcal/kg/day. The second group of 45 patients was placed on a SD that provided the same energy intake, 0.3 gm/kg/day protein, mostly of vegetdble source, and 4 mg/kg/day phosphate. The latter rEgimen was supplemented with a mixture of essential aminoacids (EEA) and ketoanalogues (KA) providing 0.2 mg/kg/Nitrogen. The following parameters were evaluated in both groups: body weight, skinfold thickness, Ht. Hb, total protein, albumin, plasma creatinine, creatinine clearance, Ca-P and acid- base balance, PTH and calcitonine. The observation period was )0 months. The slope of l/creatinine was -0.0036 in the LPD group and -0.0021 in the SO group (p < 005). PTH (MM) mean plasma levels increased from 338.6+78.3 to 456+104 pmol/l in LPD patients while they declined slightly (338.5+132 to 308.5+124 pmol/l) in SO patients. The variation from ideal body weight was 6.7\ in the LPD group and 7.5% in the SO group. AlbUmin was 4.2+1.3io the LPD group and 4.5~1.6 in the SO group at the end of the study. Besed on these results, the authors suggest that a SO appears to be more effective than a conVentional LPD in retarding the progression of renal failure. Morover, secondary Hyperparathyroidism seems to be improved by a SO. Preservation of a good nutritional status despite a long-term protein restriction does not seem to be comprORliGcd by neittler dietary regimen.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

A8

COMPARISON OF EFFECTS OF ERYTHROPOIETIN (rHuEPO) IN PATIENTS ON HEMODIAFIL TRATION (HOF) VS CONVENTIONAL HEMOOIAL YSIS (SO). S.Di Paolo, G.Catucci, L.Amoroso, M.G.Terenzio and A.Albertazzi. Inst. Of Neph., Univ. of Chieti, Italy. The use of r-HuEPO and of HDF which combines the efficient diffusive removal of small molecules of SO with the much greater convective removal of large molecules, presents possible problems of efficacy. To assess the question, 6 clinically stable patients treated with r-HuEPO were studied and allocated first to conventional hemodialysis (cuprophan or cellulosic membranes: Kd-urea 186.00.:8.00 ml/min, dialysis time: 245.00+12.24 ml/min) and then to HDF with high-flux dialysi; [polysulphone (PSF) membranes -SL627-Bellcc®: Kd-urea 279.50:1:18.50 ml/min, dialysis time: 235.00.: 12.24 min, substitution fluid NaHC03 9.0 L/4 hrs, 7.9 L/mm/3.30 hrsl. r-HuEPO was administered as i.v. bolus post-dialysis (SO or HDF) 3/week, increasing the doses (25-50 U/kg) unti I Hb levels were between 10 and 12 g%. At 6 months, no significant differences were observed in Hmt (33.8%-HOF vs 33.6%-SO); creatinine CI 286.75.:22.4 vs 170.50.:28.30 ml/min, p<.001; Kt/V 1.23.: 0.23 vs 1.01.:0.18, p: ns. There was an excellent control of some electrophysiological parameters of brain activity, while adverse reactions and hospitalizations were not greater in HOF. It is concluded that r-HuEPO can be administered safely and efficaciously to patients on SO, on HOF and that it have remarkably beneficial effects on the clinical status and on the brain electrical activity.

o 'mE CCNl'INWI' JEJUNAL RESERVOIR FOR ENl'ERAL DIALY-

SIS: SFCm.'l'ORY PROPERTIES. James F. Donovan, Jr.*, Eugene D. Kwon*, Harold P. Schedl*, John B. Stokes*, Tirrothy H. Soper*, and Richard D. Williams. Univof lA, Col of Med, Iowa City, lA. We previously reported perfusion of a 90 em jejunal Thiry-Vella loop in dogs. we found that, with perfusion, plasma solute clearance is l.imited by active solute reabsorption which maintains high plasma-to-lurren concentration gradients. Subsequently, we initiated studies of the 90 an jejunal segment isolated fran the ali.rrentary tract and configured as a reservoir accessible via a continent catheter conduit. Although constructed primarily for the study of enteral reservoir dialysis, we report the spontaneous secretory activity of the jejunal reservoir in the dog. We collected fifteen consecutive 24h secretions (mean volurre=236 ml/24h) and ShCM representative solute concentrations in the table helCM. K, Cl-, and Pi are actively secreted. NH3/NH4+ accumulates in the lumen due to ionic trapping by secreted Ht and conversion of NH3 to ionic (and rot diffused) NH4+. we conclude that the spontaneous secretory activity daronstrated by the continent jejunal reservoir provides a mechanism for clearing solutes known to accumulate in ESRD. The jejunal reservoir spontaneous secretions, in conjunction with jejunal reservoir dialysis, may supplerrent or provide an alternative to currentfoDmS of ESRD thera [.umer LJ / P Lumer1J / [PJ Cations

Na+ K+ NH3/NH4Ca++

ml4

123.1 0.8 10.9 2.4 57.4 1638.6 1.3 0.6

Anlons

cr:--HC03Pi

mM

136.9 16.7 6.7

1.2 0.8 5.3

.. RENAL EFFECTS OF HIGH- AND LOW-OSMOLAR CONTRAST MEDIA C. Donadio, G. Tramonti, R. Giordani,A. Lucchetti, A. Calderazzi, C. Bianchi. Unita di Nefrologia, Clinica Medica 2, Radiologia, University of Pisa, Pisa, Italy The aim of this study is to evaluate the renal effects of contrast media (CM) with different osmolality: diatrizoate meglumine (DIA) (a highosmolar ionic CM), iohexol (IOH) and iopamidol (lOP) (two low-osmolar nonionic CM). Fifty-seven adult patients (21-78 years, mean 51) were examined: 18 with DIA, 20 with IOH, 19 with lOP. Their mean creatinine cl was 99 ml/min (range 39- 178). Urography was performed in 50 pts and computed tomography in 7. Different parameters of glomerular and tubular function were determined in the week preceding the administration of CM and 1, 3 and 5 days after. The most frequent renal effect of all CM was the increase of urinary enzymes. In particular, mean values of alanine aminopeptidase and gammaglutamyltransferase were more than doubled on the first day after CM, while the increase of N-acetyl-~-D-glucosaminidase and lysozyme was less evident. Enzymuria resulted slightly higher after DIA. In all cases enzymes returned to base-line values within 5 days. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not show any clinically relevant impairment. In conclusion, both high- and low-osmolar CM can affect the renal tubule, as demonstrated by the increase of enzymuria. This effect is reversible and not accompanied by a decrease of GFR and ERPF. No significant difference was observed between high- and low-osmolar contrast media.

EARLY INDICATORS OF RENAL DISEASE IN PARENTERAL SUBSTANCE ABUSERS (SA); h..:. P..\IQ.rQ.w! S. Wadhwani: P. Kleln~ and N.W. Levin. Beth Israel Med. Ctr, NY. Parenteral abuse of narcotics. particularly of heroin. has been associated with a specific renal lesion. Focal and Segmental Glomerular Sclerosis (FSGS). Manifest clinically as nephrotic syndrome. hypertension. and azotemia. FSGS progresses rapidly to ESRD . The etiology of this lesion remains obscure. In an attempt to identify a sub- population of SA at risk for ESRD. we retrospectively examined the charts of 347 randomly selected healthy SA voluntarily admitted for detoxification between 1/ 86 and 12/ 89. Indicators of renal disease were azotemia (BUN>20 mg/dl or Creat.>1.4 mg/ dl). hematuria (>3 RBC/ HPF). or proteinuria (>1+ albumin on dipstick). Alcohol abusers without other SA served as a control group. 20 patients abusing marijuana. benzodiazepines or tricyclic antidepressants served as a second control population. 28 of 93 heroin abusers (30%), 17 of 186 cocaine, nonheroin abusers (9%). and 4 of 48 alcohol abusers (9%) had renal abnormalities. None of the 20 abusers of other substances had abnormalities. We found an overall incidence of renal abnormalities of 14%. Patients who are male. black and abusers of heroin appear to be at greatest risk for renal lesions. We believe that. these data warrant a prospective examination of parenteral SA of all etiologies. Evaluation early in the course of SA associated renal lesions could provide insight into the pathogenesis of FSGS and other renal diseases in these patients and possibly into methods of therapeutic intervention.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

o USE OF BIOELECfRICAL IMPEDANCE TECHNIQUES

IN THE NUTRITIONAL ASSESSMENT OF CHRONIC MAINTENANCE HEMODIALYSIS PATIENTS. Francis Dumler, Stanley Frinak,* Tom Lubkowski,* and Mark D. Faber. Henry Ford Hospital, Detroit, Michigan. Recent studies have identified inadequate nutrition as an risk factor in chronic hemodialysis patients (CHP). While protein intake may be accurately assessed in the clinical setting by urea kinetic modeling (per), evaluation of nutritional status requires skin fold measurements or insensitive parameters such as serum albumin and transferrin. We wish to report our experience with biolectrical impedance (BEl) techniques for the evaluation of body composition in CHD. BEl was measured using a four-terminal impedance plethysmograph as the resistance (RZ) in ohms (n) at an excitation current of 800 Jlllmps using 50 KHz. Hemodialysis (n=8) was associated with a continuous rise in RZ from a baseline of 45l±59 to 506±53 n at the end of dialysis(p =0.0001). The rate of increase was higher (p=O.019) during isolated ultrafiltration (0.59±O.14 Q/min) than during dialysis (0.31±O.18 ntmin) without fluid removal. All subsequent patients were studied post dialysis (mean age: 49±14 years; n=27). Total body water content by BEl was highly correlated with that obtained with the Watson equation (R=O.957; p=O.OOOI) and urea kinetic modeling (0.906; p=O.oool). Body fat content by BEl was similar to that measured by skin fold thickness (30±9 % of body weight). Body fat content by BEl in patients with body weights >2.5% below ideal body weight were lower than in patients at or above ideal body weight (23±7% vs 32±9% respectively; p=O.025). Serum albumin and transferrin values were similar in both groups. Longitudinal studies (n=13) showed a 2.9% decrease in lean body mass in patients with documented weight loss and a 1.6% increase in those who gained or maintained weight during the 3 month period of observation. In summary, BEl is a practical clinical tool for the nutritional assessment of CHD and a promising tool for monitoring interventional studies.

n

GOOD NEUROLOGIC OUTCOME IN CHILDREN mTH CHRONIC RENAL FAILURE FROM INFANCY. A.Y. Elzouki, A. Moosa, J.E. Carroll, D. Butinar. Dept. of Pediatrics, Faculty of Medicine, Kuwait university, Kuwait. Progressive encephalopathy, developmental delay, microcephaly, EEG and CT scan abnormalities have been reported in 80% of children with chronic renal failure (CRF) in infancy. Malnutrition, aluminum intoxication, and psychosocial deprivation are proposed as causes. In 15 children with CRF from infancy we evaluated the effect of no aluminum salts and early vigorous nutritional and psychosocial support in addition to the standard therapy on neurologic development. Six patients underwent dialysis (two at birth) and three received transplantation. None of our patients received aluminum therapy. Nutritional status of the patients in the first two years of life was assessed with the Waterlow classification. At the end of the follow up (mean 50 months I-range 14-148 months!), patients underwent neurodevelopmental assessment, head CT scan, EEG, nerve conduction velocity (NCV) and auditory brain stem evoked response (ABER). None of our patients developed progressive encephalopathy or recurrent seizures. All have a normal neurological examination apart from hypotonia. Microcephaly was present in 5. There was a good correlation between malnutrition in the first two years of life and occurance of microcephaly. Developmental delay was present in 3. All 3 were microcephalic and in only 3 was evidence of brain atrophy on CT scan. EEG was abnormal in 6. Only one was severe. All patients had a normal ABER. We conclude that a policy of no oral aluminum therapy and early nutritional support leads to better neurological outcome in children with CRF from infancy.

A9

ALTERATION OF GLUCOSE METABOLISM IN UREMIC PATIENTS BY A SINGLE HEMODIALYSIS (HD.) S.Ebata* , K.Tabei*, S. Namiki*, Y.Ando*, Y. Sakairi*, Y. Asano*. Division of Nephrology, Jichi Medical School, and Gotenyama Clinic, Tochigi, Japan.(Introduced by H. Jacobson) In uremic patients, although a deranged glucose metabolism and its improvement after receiving regular HD arc well known, acute change in glucose metabolism by a single HD has not been well explored. In the present study, 15 nondiabetic uremic patients on stable maintenance HD (age;5&.4±3.8y, duration on HD; 89.4±15.1mo) were chosen and the influence of a sinlge HD session on glucose metabolism was examined. After overnight fasting 75g oral glucose tolerance test (GTI) was performed measuring blood sugar (BS) and immunoreactive insulin (iRI) levels. Then HD was performed without permitting meal during the session, and GTT was performed again after HD. Insulinogenic index was calculated as MRI/!l.BS at 30min of GTT. The time course of the change in BS in GTT was normal in 9 pts before HD. But only 4 out of those 9 retained a normal GTT response after HD. PrcGTT BS and IRI was not significantly different before and after HD (BS;84.75±3.91-+ 82.94±3.97,IRI; IO.59±1. I 2-+9.66±1.48). Interestingly, although pre- and postHD MRI were not different (42.64±5.86-+ 44.29±IO.OI), post HD Ll.BS was significantly greater than preHD (50.63±7.64-+80.88±17.80; p<0.OO5). Thus, insulinogenic index was markedly depressed after HD (0.96±0.09-+ 0.69±0.I3; P
o EFFECT

OF HYPERPARATHYROIDISM ON CARPAL TUNNEL SYNDROME IN HEMODIALYSIS PATIENTS. Andrew Fenves, Ronald D. Smith, Dallas Nephrology Clinical Research Institute, Dallas, Texas. ~2 microglobulin (~2M) amyloidos~s causing carpal tunnel syndrome (eTS) ~n chronic hemodialysis (HD) patients is well recognized. In our series of 14 patients with ~2M amyloidosis, 10(70%) had a previous parathyroidectomy (PTHx) for severe 2° hyperparathyroidism (lPTH). To investigate whether there is a correlation between 1PTH and the development of ~2M amyloid CTS, we retrospectively analyzed all HD pts from 1984-1989 (mean 802/yr) for CTS and PTHx as a marker of lPTH. 283 HD pts dialyzed from 7-21 years. CTS incidence increased from 4% at yr 7 to 50% by yr 14. After 8 yrs of dialysis, a patient is as likely to have CTS with PTHx as he would without PTHx. We analyzed a second cohort of 161 HD pts diagnosed with lPTH by elevated alk phos and C/N PTH terminal (C 711, normal < 60 peq/mliN 129, normal < 10 pg/ml). 30 pts with symptomatic 1PTH received bone biopsies. Duration of dialysis 6.4 yrs. None had aluminum bone disease. Duration of dialysis 6.4 yrs. One had CTS (3%). Of the 131 pts without bone biopsy, 13 had CTS (10%). Mean dialysis 4.7 yrs. No change in dialysis membranes were made during this time, nor was there a change in management of secondary lPTH. It is concluded that lPTH is not implicated as a secondary factor stimulating ~2M to produce CTS.

A10

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

PRE-EMPTIVE PEDIATRIC RENAL TRANSPLANTATION L. Suzanne Flom,. Richard A. Cohn, E. Michael Reisman,. Mark R. Zaontz" and Casimir F. Firlit, Children's Memorial Hospital, Northwestern Univ. Med. School, Chicago, IL Renal transplantation (Tx) is the optimal treatment for most young patients with end stage renal disease (ESRD). A recent approach to treatment of children with ESRD is pre-emptive Tx, before dialysis becomes necessary. Herein we report our experience between 1984 and 1989 with pre-emptive live-related donor renal Tx in 23 children (16 boys and 7 girls) ages 2-16 years. 18 donors were parents and 5 were siblings, 3 of whom were HLA-identical. Twenty-one of twenty-three transplants (91%) are still functioning with mean follow-up of 48 months (range 5-72 months). During the same time period, 35 children on dialysis received live-related donor renal transplants at our institution; 27 of these 35 (77%) are still functioning. In the pre-emptive group, one graft was lost with chronic rejection and one with patient death due to pneumocystis pneumonia. Transplant-related complications necessitated re-exploration of three patients: one for blood clot in the renal pelvis, one for ureteral obstruction and one for suspected obstruction. One patient who developed a nonHodgkin's lymphoma three years post-transplant is currently in remission with normal transplant function. We conclude that pre-emptive renal Tx in children is a successful treatment of chronic renal insufficiency that obviates the need for dialysis in children clearly destined for ESRD. It offers advantages with regard to improved growth, decreased neurologic deficits, decreased transfusion requirements, less HLA sensitization, and less psychological trauma to these young patients. Moreover, in our experience, the success rate with Tx appears higher in those patients who were not dialyzed.

THE THOMAS SlRlNT: A FORGOTTEN VASCULAR ACCESS. Barry I. Freedman, Audrey B. Tuttle,* Robert A. Moore, and Vincent J. Canzanello. Bowman Gray School of Medicine, Winston-Salem, NC We report our experience with 57 external Thomas femoral shunts (TS) placed in 43 chronic hemodialysis patients (pts) at the North Carolina Baptist Hospital from 11/78 to 6/89. TS pts had a mean age of 56.6 years (range 22-83) and were 56% (24/4.3) black, 67% (29/43) female and 42% (18/43) diabetic. These pts had a mean of 2.8 prior vascular accesses (range 07) including 40 AV fistulae, 76 synthetic grafts, 3 Scribner shunts and 2 internal jugular vein catheters. 53% (23/43) of pts had failed peritoneal dialysis. 63% (36/57) of TS are presently functional (9 pts), or functioned until pt death from unrelated cause or removal after renal transplantation (27 pts). 28 of the above 36 TS functioned> 1 mo, mean 25.4 mo (range 3-128) and 17 have been complication-free, while 11 have had 13 in-hospital declotting procedures, 3 chronic infections and 7 revisions. 8 TS worked < 1 mo and these pts expired from non-access related causes. 37% (21/57) of TS failed after a mean duration of 17.5 mo (range 2-40). Causes and frequency of failure were thrombosis 57% (12/21), infection 24% (5/21), and failure during revision 19% (4/21). The TS remains a viable means of chronic vascular access for hemodialysis pts who cannot receive further upper arm accesses. We had no TS related deaths and the majority of the shunts functioned well for extended periods.

[] NON-CHEMICAL REPROCESSING OF POLYSULFONE HEMODIALYZERS USING HEAT RE-STERILIZATION. Stanley Frinak, * Francis Dumler, Tom Folden, * Bruce Crook,* and Nathan W. Levin. Henry Ford Hospital, Detroit, Michigan & Beth Israel Medical Center, New York, New York. Dialyzer reprocessing routinely employs chemical disinfectants and sterilants such as bleach, formaldehyde and peracetic acid. To eliminate possible hazards and environmental problems associated with chemicals, an alternative method using heat sterilization has been developed for use in polysulfone hemodialyzers. Water filled F 80 dialyzers were reprocessed with dry heat at 105 C2 for 24 hours. After 20 reprocessing cycles no resin fractures were observed and no loss of structural integrity was noted during a standard pressure holding test (n=19). In addition, no changes in small molecular clearances (Baseline: 254 ml/min at Qb & Qd of 300 & 500 mVmin respectively) occurred with up to 20 reprocessing cycles (247±5 rnIjmin, n=lO). Biological challenges using B. stearothermQphilus and Pseudomonas sp. demonstrated no bacterial growth after heat reprocessing indicated complete sterilization. In addition, testing of heat sterilized dialyzers for cytotoxicity with the mouse fibroblast cell cultures and the USP XXII rabbit hemolysis tests were negative. In summary: heat re-sterilization has no significant effects on dialyzer integrity or expected clinical performance and complies with AAMI standards for sterilization. Heat resterilization is a safe and reproducible process that avoids the associated costs and problems of use and exposure to chemical sterilants. Finally, the heat re-sterilization technique described here is practical and utilizes simple equipment.

[] CLINICOPATHOLOGICAL STUDY OF THE RENAL LESION IN POEMS SYNDROME. A.Fukatsu, Y.lto, K.Miyagawa, T. Toriyama, H.Kawahara, *A.Takeda,*K.Morozumi and **H. Shigematsu. 3rd Dept Int Med, Nagoya and *Nagoya City Univ, and **Dept Pathol, Shinshu Univ, Japan POEMS (Crow-Fukase) syndrome is a rare disorder manifesting symptoms such as polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes. Although renal dysfunction is often noticed, detailed report of renal lesion is limited. We studied 4 cases of POEMS syndrome with renal dysfunction. Three cases required hemodialysis to manage renal failure or anasarca. Corticosteroid was medicated in 3 cases and was effective in 2 cases to recover renal function. Five needle renal biopsies were performed. All cases showed microangiopathy (I~O) of various stages typically seen in hemolytic uremic syndrome. By light microscopy, narrowing of capillary lumen, reticulation of me sangial area, and duplication of basement membrane were seen. Interstitium was well preserved. In acute phase, mesangiolysis and in chronic phase, sclerosis were noticed. By electron microscopy, vesiculation of endothelial cells, migration of infiltrating cells and escape of erythrocytes into widened subendothelial space were observed. Mesangial and endothelial interposition existed. IgA, M, G, C3 or C4 was negative. Immunostaining for decay accelerating factor showed diffuse distribution in the glomerulus. Some cases had Castleman disease like pathology in lymphnodes, cutaneal hemangioma with endothelial proliferation, and microangiopathy of vasa vasorum of nerve tissue. These results suggest that chronic injury or stimulation to endothelial cells of glomeruli and of other organs might be a pathogenesis of POEMS syndrome.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS [] COMPARISON OF CHOLESTEROLS (C) AND APO B AND A-l IN HEMODIALYSIS (HD) , CAPD AND AFTER KIDNEY TRANSPLANTATION (TX). M.H. Gault, L. Longerich, V. Prabhakaran, L. Purchase. Lipid risk factors after renal TX have been reported to exceed those for CAPD & HD patients (Am J Med 87: 61M-67M, 1989). We assayed total cholesterol (TC), HDL-C, triglycerides (TG) and apolipoproteins B (Apo B) and A-l (mg/dl). Mean values for the 3 treatment groups were: N CAPI 31 HD 21 TX 91

Age 54 59 36

TC 267 220 228

HDLr.

30 29 43

TC/ -C 8.9 7.6 5.3

HnT

N Apo B 567 31 154 336 21 100 186 25 88

Tg

Apo B/A-l A-l 106 1.45 110 0.91 116 0.76

The main abnormalities in HD were high mean Tg and low HDL-C. CAPD patients also had significantly higher TC (p<.05), Tg (p<.05), Apo-B (p<.03), TC/HDL-C and Apo-B/A (both p<.05) than hemodialysis patients. The most striking differences were the lower risk mean values in the transplant group compared with CAPD for HDL-C (p<.OOl) , Apo-B (p<.002), Tg (p<.OOl), TC/HDLC (p<.02) and ApoB/A-l (p<.03). Mean values for TC and Tg were not different for TX on cyclosporine (mean dose 4.5 mg/kg/d) and on azathioprine (p>.15). The mean age of the transplant group was about 20 years lower than for the dialysis groups. However, 18 age and sex matched CAPD and transplant pairs also showed higher mean CAPD values for Tg (p<.03), TC/HDL-C (p<.003) and lower for HDL-C (p<.02). Lipid values for diabetics were not significantly different in CAPD, HD or TX from non-diabetics. In our patients, lipid risk factors were lower in transplant than for hemodialysis or CAPD patients.

TRANSFUSION REQUIREMENT IN DIALYSIS PA.."'IENTS BEFORE ERY'IHROFOIETIN (Ero) WAS AVAIIABLE: A

REASSESSMEt-'T. Fra.'1.1( D. Gutmann, * Flore..'1ce Mielke, * and Paul G. Jenkins. univ. of Viisccnsin Med. Sc.'1.., V.ilwaukee Clinical Campus, Nephrology section, and Div. of Nursing, Sir~i Samaritan Medical Center, Hilwau.1JOrtance of a 10;'ler TR as a justification for t.'1e use cf EPa.

A11

SCHISTOSOM}ASIS IN REN~L TRANSPLANTATION. A. Guleria, T. McCanty , J.A. Light, N. Khawand; S. Korb, A. Ali and M. Edson. Transplantation Services, The Washington Hospital Center, Washington, D.C. Our institution has performed a number of renal transplants in patients from countries where schistosomiasis is endemic. Schistosomal infection may result in numerous abnormalities of the urinar¥ tract, including: bladder fibros1s and ulceration; ureteral fibrosis; obstruction due to calculi formation; secondary bacterial infections; and even bladder cancer. Therapy may consist of ~harcologic intervention, bladder d1litation, or surgical construction of an ileal loo~, continent pouch, or bladder augmentat10n. From 1985 - present we have encountered schistosomal disease in 6 patients during pre-transplant evaluation, including; a sonogram of the native kidneys, VCUG, cystoscop¥ and bladder biopsy. The bladder b10PS¥ is particularly important in the determ1nation since standard urine screening mar provide false negative results. Pat1ents with active disease were treated with Praziquantel, 60 mg/kg, given orally in three divided doses over 24 hours. Those patients with contracted bladders were hydrodilated. with eradication of active disease, along with pretransplant hydrodilation, even those patients with "e~gshell" bladders can receive standard k1dney transplants without post-operative urologic complications.

CUTANEOUS CHANGES ASSOCIATED WITH END STAGE RENAL DISEASE (ESRD). Farid Haddoum* Louisa Kaci*, Asma ALLaL* and Achour Laradi KoLea HospitaL, ALgeria. The present study was undertaken in order to estabLish cutaneous changes associated with ESRD. The cLinicaL presentation and skin biopsy findings were studied in 49 patients (pts) (25maLe,24 femaLe) with rena L fai Lure (RF). The mean age is 40 years (14-74extrems). 29 pts were treated by hemodiaLysis (HD) 5 by peritoneaL diaLysis (CAPD) and 20 pts had an mean cLearance of creatinine of 12 mL/mn (6-24mL/mn extrems). The causes of RF were in 5 cases diabetes, 3 poLycystic Kidney and 1 fabry disease. HTA was present among 51% and 13% of the pts presented secondary hyperparathyroidism. The m?an time in diaLysis was 35 months (2-144,extrEms).Predominant cLinicaL symptoms are prurit (23pts, 46%) and xerodermia (22pts,45%). Biopsies were cLassified into four groups: 1- Thrombotic microangiopathy (TM,32pts,65%), 2-PerivascuLar Lymphocytar infiLtration (24cases,49%), 3- Evident epidermic atrophy,(18cases,37%), 4- Spongiosis and exocystosis (8cases). AmyLoidosis histo-chemicaL coLoration were negative in aLL cases and no intradermic caLcium deposits were noticed aLso.TM is more frequent among HD pts (75%) in comparaison with non diaLyzed pts.(50% of the 20 pts) and hypertension is not invoLved i nth e s e fin din gs. The sed a t a sup p 0 r t the concLusion of simiLar studies.

A12

o HEMXOA.GULATlOO PAAAMEl'ERS

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS IN DIALYSIS PATIENI'S

D.S.HAN, S. Y.SQ.lG, K.H e CHl.1I, H. Y. LEE Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Compared to hemodialysis(HD), patients on continuous ambulatory peritoneal dialysis(CAPD) generally show low serum albumin level secondary to peritoneal protein loss and increased cholesterol/ triglyceride levels, findings similarly observed in nephrotic syndrome which, in addition, has the features of hypercoagulability state(HS). To assess whether this HS exists in CAPD, we compared blood coagulation parameters indicative of coagulability state in 25 normal subjects, 18 HD and 23 CAPD patients. Results are shown (Mean i: SD). Normal HD CAPD Albumin, griildl '"4.5io:T 4.0 ±- 0.3 3.1 ±-D.6*Cholesterol, mg/dl 174 ± 23 147 ± 22 182 ± 27* Fibrinogen, mg/dl 212 ± 52 309 ± 88 439 ± 124* F.D.P. pg/dl 0.6 ± 2.2 1.4 ± 3.3 7.2 ± 9.9* Antithranbin -III(AT-III), IU/ ml 12.0 ± 2.1 11.3± 1.8 9.0 ± 1.6* Platelet , xl0 3/ mm 273 ± 72 170 ± 57 293 ± 83* Factor VIII, % 79 ± 28 103 ± 29 172 ± 79* * p <. 0 . 05 vs. HD Moreover, further Significant reduction in AT-III level was noted in 5 CAPD patients during peritonitis associated with increased protein loss. In summary, our data suggest that patients on CAPO have a state of hypercoagulability, particularly during peritonitis.

TREATMENT OF TRANSFUSION-DEPENDENT CHRONIC HEMODIALYSIS (CHD) ANEMIA WITH LOW DOSE ERYTHROPOIETIN (EPO) & NANDROLONE DECANOATE(ND).Ernesto D.Hendler and Lawrence R.Solomon*.Dept Med, West Haven VA Med Ctr & Yale Univ.,New Haven, CT. EPO corrects the anemia of almost all CHD pts when given in doses of 50-150 U/Kg BW IV 3x/week. Transfusion-dependent pts (1 unit of blood/month to maintain Hgb> 6g/d1)require large doses of EPO to reach target Hgb above 10g/dl without transfusions and develop complications : hypertension,39%;seizures S%; & clotting of access 14%(European Multicenter Study, Abstracts, ICN, 139A, July 15-20, 1990). We have treated all 3 transfusion-dependent CHD pts in our Center with the combination of progressively increasing EPO doses of 7.5-30 U/Kg IV 3x/ week & nandrolone decanoate (100mg 1M/week). Their baseline Hgb was 5.S, 6.S & 5.4 g/dl respectively. All 3 pts became transfusion independent on 7.5 U/ Kg within 5-S weeks. Two pts increased their Hgb 2.5 & 3.Sg/dl; the latter has reached target Hgb. The 3rd pt had increased his Hgb 1.4g/dl on 15 U/ Kg when he was successfully transplanted. None of the 3 pts developed hypertension, seizures or clotting of blood access. We have previously shown that the response to this low dose of EPO with this regimen is androgendependent (Clin Res 3S:327A,1990). Thus the addition of NO to EPO therapy may improve the anemia of transfusion-dependent CHD pts with much lower doses and fewer side effects than previously reported. Low doses of EPO(7.5-30 U/Kg 3x/week)associated with low doses of nandrolone decanoate seems to be an efficient, low toxicity and cost effective therapy for CHD patients with transfusiondependent severe anemia.

A CARE AND COST STUDY IN HYPERTENSIVE (HTN) PATIENTS WITH RENAL INSUFFIC~ENCY (RI). L.E. ~*, W.K. Tierney*, D.W. Rudy* and F.C. Luft. Depts of Nephrology and Health Services Research, Ind. Univ., Indpls., IN. We showed that black race, NIDDK and blood pressure (BP) were risk factors for progression of renal disease in 6,880 HTN patients, 20% of whom developed RI within 7 yrs (Am J Kidney Dis 13 :485,1989) . To test the hypothesis that special nephro1ogica1 care (SNC) improves outcome and lowers costs, we initiated a randomized, controlled, mUltiple risk factor intervention trial . Over 300 patients (goal 600) with RI are enrolled to date. Half have NIDDK (45% poorly controlled) and all have HTN (66% poorly controlled). Renal tests and information regarding compliance, social support, quality of life, and functional status are obtained from both intervention and control patients. The former are then seen in the SNC clinic, while the latter are returned to "usual care" in the general medicine clinic (GKC). SNC staff maintains BP
THALLIUM STRESS TESTING (TST) PREDICTS CARDIOVASCULAR RISK IN DIABETIC PATIENTS UNDERGOING CADAVERIC RENAL TRANSPLANTATION JL Holley, RA Fenton*. University of Pittsburgn, ~urgh, Pennsylvania. Controversy continues over the effectiveness of TST for assessing cardiovascular risk in diabetics before renal transplantation. We reviewed the results of TST done as the initial cardiovascular evaluation in 143 diabetic patients (pts) presenting for cadaveric renal transplantation between January 1985 and January 1989. No pt had anginal symptoms. Sixty-four pts (43%) reached 170% of maximum predicted heart rate without reversible perfusion defects or ischemic EKG changes and were accepted for transplantation (Grp A). These pts were compared with 79 pts (Grp B) who had inadequate (n=52) or abnormal (n=27) TST and subsequently had cardiac catheterization. There was no difference in age, sex distribution, mode of dialYSiS, or use of calcium channel blockers between groups. Grp B pts were more likely to be on B blockers (10/64 vs 28/79, p=0.02). Forty-eight Grp A and 52 Grp B pts were transplanted before Jan. 1989. The occurrence of perioperative myocardial infarction was not different between groups (1/48, 2% in Grp A vs 2/52, 4% in Grp B). TST is cost effec ti ve, sensitive, and predicts perioperative cardiovascular risk in a significant proportion (43%) of asymptomatic diabetics undergoing renal transplantation. B blockers limit the useful ness -of TST.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

D

EXTRARENAL CLEARANCE OF CREATININE (ECC) IN POST·OPERATIYE RENAL TRANSPLANT (TP) RECIPIENTS. ~ JA Sargent, WA Sterling and RB Freeman. Lovelace Medical Foundation,and Univ of New Mexico, Albuquerque, NM, Quantitative Medical Systems, Emeryville, CA, and Veterans' Administration Hospital, Batavia, NY. ECC, (probably by enteric catabolism) may account for 15·69% of creatinine elimination in chronic renal failure (CRF) (Goldman et al). ECC rates are proportional to serum creatinine (sCr) levels, and in a static study of CRF subjects, ranged from 0.015 to 0.071 I/kg/day, (mean 0.042 ± .0001/kg/day) (Mitch and Walser), and was unaltered by selected antibiotics. We estimated ECC in 13 post·op renailP recipients during recovery from acute tubular necrosis or acute rejection, as sCr fell ~ 50% (from 3 to 10 mg/dl, to 1.4 to 2.8 mg/dl), but dietary prescription remained constant. Subjects took 60 mg/day prednisone, and azathiaprine. Five received antibiotics for urinary infections. Creatinine appearance rates (CAR), (urine excretion +.6. body water content) were measured daily (8 to 20 observations/subject) from mass balance calculations previously described, and plotted (y axis) against sCr levels (x axis). The slope described ECe. (Mean coefficient of variation of 11% of CAR during periods of stable renal function validated technical accuracy.) Over the study period, as sCr fell, CAR rose 8·95%, average 29%. Correlation coefficients (CC) ranged from 0.54 to 0.90, and were ~0.7 in 9 subjects. ECC ranged from 4.3 to 11.7 I/day, mean 7.21 ± 2.9 I/day, or 0.11 ± .004 I/kg/day. ECC was similar in subjects with CC <0.7 and ~0.7, in those recovering from A TN and from rejection, and in those receiving antibiotics, and was not age·related. One subject had identical ECC during separate periods of recovery from ATN and rejection (7.9 I/day). ECC, its relationship to sCr, and its resistance to antibiotics are confirmed in TP subjects, but the range is broader and the mean is more than twice that described in stable CRF. Explanations, and the role of steroids are unexplored. ECC can make a major contribution to creatinine elimination at high sCr levels, and reduces the value of creatinine as an index of allograft function in such subjects.

SEQUENTIAL IMMUNE MONITORING CAN AID IN THE ASSESSMENT OF RENAL ALLOGRAFT STATUS. Jan Jacobitz,· Suzanne Flom,· Richard A. Cohn, Casimir F. Firlit, Children'S Memorial Hospital, Northwestern Univ. Medical School, Chicago, IL. Monitoring renal transplant patients is challenging and complex. Primary concerns include changes in allograft function which may be related to rejection episodes, infection or cyclosporine toxicity. The use of specific surface markers by flow cytometric enumeration of lymphocyte subsets can aid in the differential diagnosis of changes in allograft function. Sequential studies of immunologic events are most valuable when carefully assessed and when correlated with clinical status and routine laboratory results (e.g. BUN, serum creatinine, B2 microglobulin, cyclosporine levels). Data suggest that T inducers of help [CD4+, CD29+ dual stained cells, Tih] are not significantly different in those renal transplant patients with decreased function (DRF), n=6, when compared with a group of stable renal allograft patients (SRA, n=IO). However, there are significantly higher numbers (P<0.05, Student t-Test) of T inducers of suppression [CD4+, CD45RA+, (Tis)] cells in SRA (1428 mean cells/ul) versus DRF (589 mean cells/ul). Tih/Tis ratios are decreased (0.44) in SRA when compared to DRF (0.76). Furthermore, sequential studies for individual patients show that this ratio may dramatically increase during acute rejection episodes. These preliminary data suggest measurements of Tih/Tis ratios may aid in the differential diagnosis of rejection versus cyclosporine toxicity, and in the recovery phase from acute viral infection, common in the first few months post-transplant. Our experience indicates that changes in specific lymphocyte numbers may occur earlier than changes in serum creatinine or B2 microglobulin.



A13

ERY'I'HIDPOIEI'IN DOES Nor IMPROVE GOCWl'H IN CHIIDREN WITH FNDSTAGE RENAL DISEASE.

Leonard C. HyIres, lIDbin Davis*, Bertha Clowers * ,

Ehory University School of Departrrent of Pediatrics, Atlanta, GA. Adult patients with endstage renal disease reportedly show an increase in appetite and physical stamina when receiving treatment with erythropoietin (EPO). we postulated that children with endstage renal disease would experience similar benefits and would derronstrate improved linear and anthropcnetric grCMth as a result of increasing their Hct% with EPO. we rreasured height (ht), height age, bone maturation index (trni), triceps skin fold thickness (tsf), mid-ann circumference (mac) and mid-ann Imlscle circumference (marte) in 10 children (age 9.3 + 4.8 years) before and after 6 + 2 rronths of Efu therapy. Barry L. warshaw.

~iicine,

Pre EPO Hct %

Ht age - yrs BMI

Ht - z score TSF - z score MAC - z score MAM: - z score

22 ± 2 7.2 + 5.1 0.7 ±. 0.3 -2.1.±.2 . 7 -0.7 ± .8 -0.9 ± 1.2 -0.5 ± 1.5

EPO

30 7.2 0.7 -2.3 -0.6 -1.0 -0.6

± 3 ±. 5.0 ± 0.3

.±. 2.6

±

.·1.1 ±. 1.1 ± 1.4

p<.Ol ns ns ns

ns ns ns

There were no differences in serum concentrations of K, ca, P or BUN before versus after treatment with EPO. From these results, we conclude that children treated with EPO do not experience inproved linear or anthropcnetric grCMth despite significantly higher Hct%.

D

mJRl'lUS (PR) IN DIALYSIS PATIEm'S (OP) IlJE 'IO IRf::N (Fe) DEFICIENCY. Paul G. Jenkins, univ. of Wise. Mad. SChool, sinai Samaritan Mad.

ctr., Milwaukee, Wisconsin.

PR cxx:urs in a majority of OP sane time As a rule, no specific cause of PR is identified am no specific or uniformly effective treatment exists. We have evaluated 6 episodes of severe PR in 3 DP with each episode associated with a decreased senm\ ferritin level. '!he PR ilrproved within several weeks am resolved oanplete1y within 1-2 months after Fe therapy. 'nIo henv::xlialysis am 1 CAPO patient had 3, 2, am 1 episodes of PR am had been on dialysis 84, 54, am 11 lOOTlths respectively before PR first developed. Fe dextran (1 gIn) was given to the helOOdialysis patients am oral Fe to the CAPO patient. Pertinent hematologic data are summarized: Hct MCV Ferritin Mean 46% 84 34 n:J/ml Pre Fe Range 27-55% 74-88 <5-76 Mean 44% 84 154 Post Fe Range 26-55% 75-90 93-206 We have seen numerous other episcxles of PR in other OP associated with lC1\\1 ferritin levels am which resolved after Fe therapy. It is possible that Fe deficiency :in:luced by ezythropoietin use may increase the incidence of PR in OP. We conclude: (1) Fe deficiency can cause PR in OP. (2) Neither anemia nor microcytosis need be present. (3) Response to Fe therapy is relatively rapid am oanplete. (4) Fe deficiency may be the nost CCl1'alOIl specific cause of PR in OP.

durin; their illness.

A14

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

COLCHICINE INDUCED MYONEUROPATHY IN A RENAL TRANSPLANT PATIENT. Johann Jonsson: Juan R. Gelpi~ Jimmy A. Light, Alexandro Aquino and Scarlett Maszaro~ Transplantation Services, Washington Hospital Center. Washington, D.C. 20010 A 55 year old male, with end stage renal disease from amyloidosis received a cadaveric renal transplant. Prior to his transplant he was on colchicine therapy for the amyloidosis. This was stopped prior to transplantation, but was restarted one month after surgery. Four weeks later, the patient exhibited s~ptoms of severe muscle weakness, along w~th diarrhea and abdominal discomfort. He was admitted to the hospital, and an electromyographic and nerve conduction studr (EMG/NCS) were performed. These stud~es were consistent with colchicine induced myoneuro~athy. The patient's colchicine was d~scontinued, followed by immediate symptomatic improvement and by declinin9 levels of CPK. It is hypothes~zed that the colchicine toxicity was the result of insufficient elimination, secondarr to cyclosporin nephro- and hepatotox~cities.

SINGLE DOSE REPONSE KINETICS OF ORAL CYCLOSPORINE A: A CRITICAL REEXAMINATION. R. Klauser'. H.Irschik" J. Wolfram', W.W oloszczuk·, E. Pohanka', J.Kovarik' (intr. by M.R. Garavoy). , Dept of Med II, Univ of Vienna; Inst. for Mechanics, Techn. Univ. Vienna, Austria. Pharmacokinetic monitoring of cyc1osporine A (eyA) is still a crucial problem in inununosuppressive therapy. We therefore measured eyA levels by polyc1onal TDX method in short intervals for a 36 hour period following oral administration of 5 mg/kg and 8 mg/kg eyA, respectively. The study was performed in 10 patients with end stage renal failure under controlled dietary conditions. eyA levels were smoothed according to a twocompartment model demonstrating a first-order absorption kinetic curve. n 12h Nr Dose CyAmax Tmax il min h- 1 ng/m1 mglkg ng/m1 h- 1 1 2 3 4 5 6 7 8 9 10

5 5 5 5 5 5 8 8 8 8

1058 1106 799 839 847

609 2033 2054 1836 2194

300 120 240 60 420 60 150 240 300 90

0,033 0,490 0,202 0,ol8 0,025 0,011 0,356 0,061 0,295 0,009

0,216 0,450 0,327 0,250 0,234 0,241 0,393 0,270 0,361 0,247

414 140 230 170 250

58 294 508 327 336

The results of our study indicate a wide variation in the fractional absorption rate as well as in absorption time (Tmax, il) after oral eyA, whereas the slope of elimination (Q) remains relatively constant. These findings might explain differences in dose requirements in the individual patient and suggest that trough levels measured after 12 hours (Uh) are not representative.

TRANSPLANT PATIENTS AS ORGAN DONORS. S. Korb, A. Guleria~ J. Jonsso~i A. Ali, M. Pustay*and J.A. Light.Transp ant Servo Washington Hospital Ctr, Washington, D.C. Although transplantation is the most effective thera~y for patients with ESRD, the number wait~ng to receive renal allografts is increasing faster than the number of donors. Recipients of extrarenal allografts have been an unusual source of donor kidneys, although with the increasing number of successful extra-renal transplants, the events reported herein may become more common. The donor was a 59 year old male who received a liver transplant at another institution on 3/20/89. Immunosuppressive therapy included OKT3, prednisone and CyA. The patient expired on 8/2/89 due to a cerebral vascular accident and became a kidney donor, (SCr-1.0mg/dl). The two renal recipients were both male, 27 and 34 rears old, both sharing 4 out of 6 HLA ant~gens with the donor. Both received OKT3 along with prednisone, azathio~rine and CYA. After I year, renal funct~on has been stable but marginal,scr=2.3 and 3.0 respectively. The kidneys have tolerated CyA therapy very poorl¥, with mean doses of 1.5-1.7mg/kg. Ser~al needle biopsies reveal mild to moderate patchy interstitial fibrosis consistent with chronic rejection and/or CYA toxicity. Aside from the confounding effects of rejection, the previous exposure to CYA seems to have impaired the baseline renal function. In conclusion( transplant patients who suffer bra~n death may be a donor source for kidneys ~rovided that biopsies be performed ~r~or to implant to assess the baseline m~croscopic structure to help evaluate post-transplant events.

[] MAINTAINING ADEQUACY OF PERITONEAL DIALYSIS BY EMPLOYING A PATIENT SPECIFIC TREATMENT PROTOCOL. Randi Kr a pf*,Paul M. Zabetakis, Maria V. DeVita , Susan Kochavi, Michael F. Michelis, Nephrology Section, Lenox Hill Hospital, New York, New York. Continuous ambulatory peritoneal dialysis (CAPD) or nighttime exchanges with a day time dwell (CCPD ) represent efficient modalities for dial ysis in s elected patients.The peritoneal equilibra tion test (PET)is used to assess peritoneal membrane transport characteristics. While Twardowski has advocated a combined renal and peritonea l clearance of 40-50 L/wk(approximately 6L/day)to achieve adequ at e dialysis, guidelines f or patient s pe cif ic tre a tment protocols(PSP) are lacking. By employ ing eac h patient's measured PET and the sta ndard dial ys a t e clearance formula (C=D/p,v; where C=peritoneal clearance, D=dialys ate creatinine,P=plasma crea tinine, V=dialysate volume) ,a PSP was calculated f or each patient.To calculate a PSP,the 2 hr Dip creat. was used f or CCPD and the 4 hr value used for CAPD . A clearanc e of 6L/day was the goa l of the PSP and used to prescribe the da ily dial ys ate volume(V) in liters as shown in the following 4 p atients: Transport CCPD CAPD Rates 2hr Dip V 4hr Dip V Low 0.28 21.4 0.47 12 .7 Low Avg . 0.36 16.6 0.62 9. 6 High Avg. 0.49 12.2 0. 70 8.5 High 0.60 10.0 0.91 6 .5 Based on our experience with 25 patients: 1) a n individualized PSP best predicts suitability f or CCPD,CAPD or hemodialysis, 2)dialys a te volume requir ements vary sign i ficantly when the appropriat e Dip value is considered, and 3) a PSP assures adequa c y of dialysis while addre s sing the i s sues o f cost and length of treatment.

A15

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS •

EFFECT OF ERYTHROPOIETIN (EPO) ON PANEL REACTIVE ANTIBODY (PRA) LEVELS AND TRANSPLANT OUTCOME IN HEMODIALYSIS PATIENTS. Warren L. KUllinj(.K. Venleat, Carolyn 10hnson",Marlene Kijewski" Martin Mozes. Division of Nephrology and Hypertension and Department of Transplantation Surgery, Henry Ford Hospital, Detroit, MI. The initiation and perpetuation of high PRA levels in potential renal transplant recipients has been related to antigenic exposure from previously rejected allografts, blood transfusions and prior pregnancies.We investigated the effect of discontinuation of blood transfusions through the introduction of EPO on the PRA levels and outcome of transplantation in 25 hemodialysis patients (17 primary and 8 repeat transplant recipients). All patients were transfusion dependent receiving 1.4±O.9 units blood/month for the 1 year preceding use of EPO however, after the first 3 months of EPO administration all patients were completely transfusion independent.The average intravenous EPO dose was 4000 unitsl3X week.Prior to initiation of EPO each patient's PRA value had remained within 10% of the pre-treatment value for a period of 6 months.At 2 years followup : PRA . Post-EPO PRA : Pre-EPO all patients(%) 47±30 19±17'" I3±9. 36±21 10 recipients( %) 30±18"'§ repeat recipients( %) 62±23 § 31±2%* HCT 23±3% • p
o CONTINUOUS VENOUS-VENOUS HEMOFILTRATION (CVVH): AN

ALTERNATIVE TO CAVH IN THE MANAGEMENT OF ARF. RL ~, BA Mueller·, SK Scarim·, & OW Rudy· (intr. by TO McKinney). Depts. of Medicine and Pharmacy, Indiana University School of Medicine, Indianapolis, IN, and Dept. of Pharmacy Practice, Purdue University, West Lafayette, IN. CA VH is being utilized with increased frequency to manage critically ill patients with ARF. CVVH, utilizing a roller pump to provide blood flow, may have advantages over CAVH by providing a more predictable ultrafiltration rate (UFR) , better control of azotemia, and less vascular and hemorrhagic complications. We retrospectively reviewed our 16 month experience with CVVH to determine if our mortality and complication rates compared favorably to those reported with CA VH. The CVVH system utilized a single dual-lumen venous catheter, a bubble trap and detector, an in-line pressure monitor. and an ultrafiltrate pump. CVVH was managed by the ICU nursing staff. Twenty five critical.ly ill patients (> 90% required both ventilator and vasopressor support) were treated for a total of 193.5 days (7.7 ±. 10.3 SO. range 0.S-48 days). The mean blood flow rate was 148 ± 38 ml/hr with an UFR of 879 ± 300 mL/hr (range 500-2000 mL/hr) . The average weight change was -7.9 ±. 7.0 kg (range -26.5 - +2.9 kg). The mean heparin requirement was 6.5 ±. 4 .2 IU/kg/hr . Seven patients survived their episode of ARF (28%) although 3 died prior to their d ischarge from the hospital. Control of azotemia (BUN < 100 mg/dL) was obtained in all patients in whom CVVH was un interrupted. Four episodes of volume-responsive hypotension. related to inappropriate ultrafiltrate replacement. occurred during the 193.5 day treatment period. Only one patient experienced a hemorrhagic complication (4%). This rate compares favorably to those for CA VH (20-40%). possibly as a result of a lower average heparin dose (6.5 vs IO IU/kg/hr). There were no vascular access complications or episodes of air embolization. Our experience indicates that CVVH is an effective renal replacement therapy in critically ill patients and may have advantages over CAVH.

ERYTHROPOIETIN ASSOCIATED HYPERTENSION . Stuart E. Baskin", Urnrana Ahmed*, and Norman Lasker. UMIlNJ, Newark, NJ. The use of erythropoietin (rHuEPO) has become almost universal among chronic hemodialysis units. Reports of the efficacy of Erythropoietin (rHuEPO) in i""roving the anemia associated with renal failure and patient rehabilitat i on have been punctuated by observations of accelerated hypertension sometimes leading to encephalopathy. This hypertension has been postulated to resul t from the increase in red blood cell mass and the resultant increase in blood vfscosity, a decrease in hypoxic vasodflatation or an increase in binding of the endothelial derived relaxant factor, nitric oxide, by the elevated h"""'!llobin . \Ie have followed a large nlJ1Iber of chronic hemodiatysis patients who are receiving rHuEPO (2S units/kgm) acininistered intravenously three tiR. a week. Several patients were identified with a distinct rise in blood pressure with no increase in hematocrit or hemoglobin. They showed no increase in body weight due to circulatory overload. All of the patients were black: with a prior history of hypertension. Antihypertensive medications had to be restarted or increased. The table below is an illustrative sa""le of these patients: I

Pt. BH

Post EPO

Pre EPO Wt. Hct

Hb

B/P

Rx lit. Het

Hb

BP

Rx

1~126.019.+S0/80 jHP I162 22.+.+80/90jHP

EJ

160 17°126.218·TSO/80 1- - 1 24 ' T'T80/90 ICD

JB

169122. 7 6.9140/80 1- - 16922.07.5150/90 IN

AC

19827.5

,,,. "'/".' '" 1'' ' 001' '"''·'1'·+''''' I" 9.S!140/90

P

1982S . 1!8.7!160/110!ENP

Drugs-;-N=Nifedipine; L=LopresS;;;:; C;;Ctonidine; E=Enalapri l; P=Propanolol; M=Minoxidil; O=Oilt;azem . " rHuEPO started after fall in hematocrit due to blood loss_ The increase in weight was a function of iq:>roved nutrition. This observation suggests that rHuEPO associated hypertension is not necessarily a function of increased hematocrit. Further investigations are necessary to est~bl istl the etiological factors underlying this phenomenon both on the eet lular and systemic level.

o NON INVASIVE STUDY OF PULMONARY WATER AND

CAPILLARY FLOW IN HEMODIALYSIS PATIENTS. N Glez Manqado*, G Blum*, G Peces-Barba*, A Ortiz*, MP Garron*, JJ Plaza*, S Casado*, L Hernando, C Caramelo*. Dialysis Unit and Respiratory Laboratory. Fundacion Jimenez Diaz. Madrid. Spain. The hemodialysis (HD)-related variations of the pulmonary water volume (PWV) and pulmonary capillary flow (PCF) were studied by the rein halation of soluble inert gases. Functional pulmonary tests were simultaneously performed. Six patients were studied in 2 days: pl'evious to HD1, pl'e-HD2 and immediately postHD2 (HD2= 72 after HD1). Other six patients were studied in 1 day: pre HD, immediately post HD and 4 hs after HD. Pre-HD1 PWV was 572 ± 70 mi. In the Interdialytic period, PWV did not significantly increase, except in a patient with myocardial dysfunction (PWV 40.7 ± 14.5 ml for all the patients, 229 ml for patient 1). The PCF, superposable to cardiac output, increased more than 35% (p< .01) between HD1 and HD2, except in the same patient 1 (increase 9.2%). PCF decreased during HD in all the patients (PCF 455±107 ml, p< .01). A decrease of more than 500 ml was associated with symptomatic hypotension in 4 patients. Four hours after HD, PCF increased significantly with respect to the end of HD (+12.5%, p<.05). The functional respiratory tests significantly improved with HD (p< .01). In conclusion: 1) In the interdialytic period PCF and therefore cardiac output increased adequately, except in the case of myocardial dysfunction; 2) in the same period the patients with normal myocardial function did not accumulate pulmonary water, therefore revealing a well functioning mechanism against pulmonary edema; 3) reduction of PCF during HD results in hypotensive symptoms only if higher than 500 ml; 4) the improvement of functional respiratory tests with HD is not directly related to changes in the total volume of pulmonary water.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

A16 •

MACROMOLECULES AND SOLUTION PROPERTIES INFLUENCE CALCIUM OXALATE CRYSTALLIZATION Manne JS and Smith AD Dept. Urology, Long Island Jewish Med. Ctr., New Hyde Park,N.Y. We looked at the influence of dissolved macromolecules and initial calcium and oxalate concentrations on the crystallization of calcium oxalate • The hydrate form of calcium oxalate which crystallized (mono, di or trihydrate, referred to as COM, COD and COT) was a function of both macromolecule concentration and initial oxalate and calcium concentrations. At 1.5 mM (millimoles) oxalate and 4. OmM calcium COM crystallized at low concentrations (0 to 2.5ppm (parts per million» of a model macromolecule poly (acrylic acid) (PAA(L». COT was the dominant product at 2.5 to 50 ppm and COD above 50 ppm. At higher oxalate (3.0 mM) and calcium concentrations (8. OmM) the transition went from COM (0-2.5 ppm PAA (L» to COD at higher PAA(L) (2.5-100 ppm). At lower oxalate concentrations (0. 8mM oxalate, 2.5 mM calcium) COT crystallized at lower macromolecule concentrations (0-2.5) and gradually COD become the predominant product at higher concentrations (>2.5ppm). Similar results were observed with the urinary polymer chondroitin-6sulfate and with pentosan polysulfate a known inhibitor. The mechanism for hydrate variation was found to be closely related to that for crystallization inhibition. In the results suggest a model for the distribution of COD and COM crystals in crystalluria.

o RESOLUTION OF PROTEINURIA SECONDARY TO BILATERAL RENAL VEIN THROMBOSIS AFTER THROMBOLYTIC THERAPY

Brian R. McDonald,* Ellen C. Morrissey,· and Gary M. Rabetoy. Dept. of Int. Meel., Naval Hospital, San Diego, CaUfornia. Renal vein thrombosis (RVT) in adults is usually diagnosed in patients with the Nephrotic Syndrcme. We report a case of significant proteinuria that occurred as a resut t of bilateral RVT secondary to dehydration from gastroenteritis, that resolved after treatment with urokinase. The patient was a 22 year old black male ~~tf': ~~

pre'!iou:::.:

h~=tO:'"i'

of th:-a:;:,s:; .:;r iE,t5l

':':i';Go~c. n~ Jt:vc~~

nausea and vomiting 3 days prior to aanission and had been diagnosed with viral gastroenteritis after an ,..-,remarlc.able evaluation in the Emergency Room_ one day later the patient noted continued nausea and vomiting, and the onset of aching lower abdominal and flank pain_ His initial physical exam was unremarkable_ Laboratory studies on adnission revealed normal electrolytes, a ser ... creatinine of 1.7 mg/dl, and 4+ proteinuria on urinalysis. An IVP showed delayed excretion bi laterally. Renal ul trasound showed normally-sized kidneys without obstruction. A 24 hour urine collection revealed 2.34 gr8fllS of protein. Urine cul ture was negative. A renaL venogram demonstrated bilateral RVT without involvement of the inferior vena cava. Therapy was initiated with heparin at 1000 units/hr after bolus injection. The patient was transferred to the ICU and he was given urokinase, 4400 units/kg bolus, followed by 4400 units/kg per hour continous infusion, with an increase to 5000 units/kg/hr after 5 1/2 hours to augment the thrombolytic state. Total duration of initial thrombolytic therapy was 12 hours. A repeat renal venogram done at this time showed partial resolution of thrombosis bilaterally. A second 12 hour infusion of urokinase at 5000 units/kg/hr was performed. During this time the patient reported complete resolution of his flank and abdominal pain. Heparin was restarted and continued for 4 days. A repeat 24 hour urine collection showed 60 mg protein with a normal creatinine clearance. Levels of antithrormin 3, protein C, and protein S were all normal. The anticoagulant therapy was stopped and a renal bi opsy was performed to rule out a meri)ranous glomerulo· nephritis. The specimen revealed normal histology on light, il1llUl1O-

flourescent, and electron microscopic evaluation. The patient has

dON! well on no thl!fl!!PY,

~r.d ~!!!

had no

!'"~!.!!"'~ertee c~

t!"::"'c.-::bosis or

proteinuria after 2 1/2 years. We could not identify any other risk factors to account for the patient's RVT except dehydration secondary GI fluid loss. This is not unconmonly seen in infants, and has been reported in adults. We believe that this case demonstrates 2 points, that dehydration is a contributing risk factor for RVT in adults, and that RVT can cause proteinuria in the absence of underlying renal disease.

NEW BLOOD PURIFICATION EXTRACORPOREAL METHODS AND B2-MICROGLOBULIN {B2M} REMOVAL. R. Marangoni, F. Civardi ,* F. Masi: R. Savino~ R. Cimino~ R. Colomb6. Nephrology and Dialysis Unit,Ospedale di Bollate, Bollate-MI, Italy With the purpose of finding the most efficient method for the removal of B2M {determined also like a marker of large molecule removal} we calculated B2M clearances {cl} in different groups of chronic uremic patients undergoing the following methods: Acetate Free Biofiltration {AFB} , High Efficiency Paired Filtration Dialysis {HEPFD}, Hemofi1tration (HF) with some membranes: Polyacrylonitrile {PAN}, hydrophobic Poliamide {HpbPA}, Polysulfone {PS}, hydrophilic Poliamide {HplPA} and HF {PS or HplPA} combined with charcoal Hemoperfusion {HF+HP} in series. B2M cl were high in HF with HplPA {90±3 ml!min~ and with PS {74±3}. HEPFD {60±2} and AFB {30±4} follow in order. HF with PAN {8±1.4} and with HpbPA (4±1.5) gave very low values. On the contrary HF+HP method gave very high B2M cl eitner with PS {147±10} or with HplPA (156±15). B2M predialytic serum levels did not show significant modifications (follow up of 12 months) in patients treated with AFB, HEPFD, HF PAN, HF HpbPAj they showed a slightly significant decrease (p<0.05) in patients undergoing HF with PS or HplPA and a highly significant decrease {p(O.001}in patients treated with HF+HP.

o PANCREATITIS

IN CHILDREN UNDERGOING CONTINUOUS CYCLING PERITONEAL DIALYSIS (CCPD). Michelle A. Meehan*, Susan B. Conley, Ronald J. Portman, and Jacques M. Lemire*. Dept. of Pediatrics, University of Texas Medical School, Houston, Texas. Seven episodes of pancreatitis complicated the course of 4 patients (pt)(2,7,10,15 yrs) treated with CCPD for 2-26 mo (x-16mo). Presenting symptoms included abdominal pain, nausea and vomiting. Of 7 episodes, 3 were associated with acute peritonitis (S.aureus(2) and P.aeruginosa), 1 followed ethmoid sinus drainage, 1 post transplant nephrectomy and 1 was diagnosed at autopsy. Intraperitoneal antibiotics (cephalothin, vane., tobra. or ticar.) were given in 6 instances. Dialysate dextrose concentrations were <3.0% in 4; >3.9% in 3 pts. At presentation, serum calcium 9.2 to 13.5 mg/dl (x-ll.O), peak serum amylase 259511,000 U/L (x-5351 U/L) , chol. 175-222 mg/dl and trig. 177-328 mg/dl. Enlargement of the pancreas was more often detected by CT scan than by ultrasonography (3/5 vs 1/5). A pseudocyst of the pancreatic tail was noted in 1 pt. Treatment included pt controlled analgesia, nasogastric drainage and total parenteral nutrition. Hemodialysis was instituted in 5 of 7 episodes with resolution of pancreatitis in 4 of the 5. The 5th pt died of presumed sepsis 1 month after diagnosis. 1 pt who was incidentally found to have pancreatitis at autopsy died of a drug reaction. At follow-up (13 mo), 1 pt underwent a successful renal transplantation despite persistance of pseudocyst and 1 pt remains on hemodialysis. Pancreatitis is a rare but ominous complication of CCPD. Peritonitis, infection, CCPD and/or hypercalcemia may trigger the onset. Hemodialysis should be considered as a therapeutic modality.

A17

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS •

OKT3 MONOCLONAL ANTIBODY VS ANTITHYMOCITE GLOBULIN IN THE TREATMENT OF STEROID RESISTANT ACUTE RENAL RFJECTTION IN PEDIATRICS; Manuel ~chon*, Bruce Kaiser*, Martin Polinsky*, Seth Schulman, Sharon Bartosh*, H. Jorge Baluarte, Dept. of Ped. , Temple Univ. Sch of Med., Phila., Pa. Comparison of 42 children who had received either Antithymocyte Globulin(ATG) or Murol!Dnab-CD3 (OKT3) in the treatment of acute renal allograft rejection resistant to high dose steroids. Reversal of rejection was successful in 16 of 18 patients (89%) treated with OKT3 and 18 of 24 (75%) treated withATG (p=ns). Rerejection episodes within 1 month of therapy occurred in 8 of 16 patients treated with OKT3' but only 2 of 18 treated with ATG (p<0.05). In 6 of the 8 patients with OKT3' and 1 of the 2 with ATG, rerejection responded to a repeat course of high dose steroids. Therefore, the incidence of graft loss due to initial rejection or rerejection within Immth post therapy was 22% for the CKT3 and 29% for the ATG group (p-ns). Graft survival was similar at 6 I!Dnths: 72% for OKT3 and 66% for ATG treated patients (p=ns); 100% patient survival was noted in both groups. Renal function using Schwartz Formula (Pediatr 58: 259,1976) evaluating mean group calculated creatinine clearance (ml/mln/ 1. 7ln2) was 64 and 70 pre-rejection; 25 and 23 during rejection; 69 and 70 at 1 month; and 67 and 72 at 6 months post rejection, in the Clcr3 and ATG treated groups, respectively. Neutropenia and thrombocytopenia occurred more frequent in the ATG group, but there was 00 significant difference in infectious complications. Two patients developed high (:;'1: 1000) OKT3 antibody titers. We conclude that OKT3 and ATG are equally effective for the treatment of steroid resistant acute renal allograft rejection in children when compared for 6 month graft survival, level of renal function and infectious complications. However, the use of ATG resulted in a lower rerejection rate.

o DIALYSIS

UNIT PRACTICES AND POJ.ICIES ABOUT LlfESUSTAINING TREATMENTS. AH Moss, CB Stocking,* GA Sachs,* and M Siegler.* University of Chicago, Chicago, IL and West Virginia University, Morgantown, WV. The re is a consensus that patients have the right to forgo life-sustaining treatments such as cardiopulmonary resuscitation (CPR) and dialysis. We surveyed medical directors of a random sample of dialysis units (N=524) in all 18 ESRD Networks to determine: 1) if unit personnel usually discuss and clarify advance directives with competent patients and 2) whether they respect such dire ctives if patients become incompetent. Directors of 318 of 524 units (61%) responded. In t.he past year, one or more cardiac arrests occurred in 71% of units. At least one patient was wit.hdrawn from dialysis in 78%. Po.licies for Do Not Resuscitate (DNR) orders exist in 31% of units (45% of hospital--based vs 21% of free--standing, p< 0.001), for withdrawal of dialysis in 15%, and for ohtaining advance directives in only 8%. Although a minority of units have written policies, routine discllssions with patients about DNR status are held in 58% of units, about withdrawal of dialysis in 63%, about living wills in 40%, and about durable powers of attorney for health care in 15%. Surprisingly, in 35% of units, patients undergo CPR even if they have a DNR order. We conclude t.hat most units face decisions about CPR and withdrawal of dialysis. In many units, current l'l'actices and policies fail to identify or to respec t patients' wishes. Dialysis units should encourage discussions to determine the wishes of patients and their advance directives so that t.heir wishes may be respected should they become incompetent.

USE OF ERYTHROPOIETIN (EPO) IN CHILDREN USING 3 ROUTES OF ADMINISTRATION. B. ~., B. Brouhard, R. cunringham, E. Paganini. Department of Ped iatrics and Section of Dialysis, Cleveland Clinic Foundation, Cleveland, Ohio. EPO therapy has become widely used to treat the anemia of end-stage renal disease. We studies 3 different routes of administration of EPO in 16 patients who were anemic with ESRD. There were 10 males and 6 females with a mean age of 16.5 years (±4.7 SO). Fourteen patients were started on 50 u/kg/dose IV or SQ given 3 times per week. Doses were adjusted depending on hemoglobin Hgb (gm/dl) and Hct (%). Two patients received intraperitoneal EPO at a dose of 150 u/kg once a week. One patient with SS disease did not respond because of biopsyproven myelofibrosis. PT.

6" 7 2

ROUTE

S.II. l.V. J.P.

PRE-HGB/HCT

7.8!.O.8/23.2:2.5 7.3:1.4/26.3:3.5 6.2/18 . 5

POST-HBG/HCT

10.4:1.7/31.4:4.8 8.9:1.4128.4:4.6 7.5:23.5

FOLLOW-UP MONTHS

11.8:8.7 4.6+2.9

I;

Serum ferritin levels dropped from 1126 ± 774 to 310 ± 305 (n=4) ng/ml~ Although peak EPO levels 8 hours after I.P. infusion ranged from 101 to 725 mlu/ml in the I.P. patients, their Hgb was lower than the I.V. or S.Q. However, we conclude that all 3 routes can maintain acceptable levels of hemoglobin.

POLYMICROBIAL BACTEREMIA IN CHRONIC HEMODIALYSIS PATIENTS. Laura L. Mulloy, Ralph J. Caruana, John C.H. Steele Jr and James J. Wynn. Medical College of GA, Augusta, GA. Bacteremias are polymicrobial in 6-14% of all cases but uremia has not been considered an important risk factor for polymicrobial bacteremia. We reviewed our hospital's epidemiology reports from July 1987 to January 1990 and identified 24 episodes of bacteremia in 22 hospitalized patients on our nephrology service who required hemodialysis. In five cases (21%) more than one organism was isolated on blood culture. Organisms isolated included S. aureus (1 isolate), streptococci (1 isolate), S. coagulase negative (1 isolate), acinetobacter (2 isolates), Klebsiella (1 isolate), enterococcus (1 isolate), E. Coli (2 isolates) and enterobacter (3 isolates). All 5 patients were on chronic hemodialysis and 4/5 had central vein dialysis catheters. The presence of symptoms, fever and leukocytOSiS was variable. No patient had obvious peri - access infection, visceral infection or evidence of endocarditis even though numerous risk factors (COPD, GI disease, SLE, HIV infection, diabetes mellitus) were noted. One patient died but the other four recovered after catheter removal and appropriate antibiotic therapy. Chronic hemodialysis patients appear to be at increased risk for polymicrobial bacteremia and this should be taken into account when prescribing empiric antibiotic therapy for presumed sepsis in this patient group.

A18

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

FATAL LYMPHOMA DURING OKT) THERAPY DIAGNOSED BY ALLOGRAFT BIOPSY. Brian Murray, R.Venuto, R.Kohli, S.Anthone, E.Cunningham, J.Gerbasi* and J. Brentjens*. SUNY at Buffalo, Buffalo, New York. Immunosuppressed renal transplant recipients are at increased· risk to develop lymphoproliferative disorders. We report two patients who presented with fever and graft dysfunction during the ~d week of OKT) therapy for rejection. Biopsy of the graft revealed malignant lymphoma. OKT) was started 42 and 70 days post-transplant for an initial rejection episode that was steroid resistant. Despite allograft nephrectomy and withdrawal of DDnmosuppression, both patients deteriorated rapidly with hepatic failure, pulmonary insufficiency, disseminated intravascular coagulation and died 62 and 86 days post-transplant. One patient had a clinical presentation consistent with acute mononucleosis and the second had evidence of prior EpsteinBarr Virus (EBV) infection. The temporal relationship between the onset of lymphoma and the use of OKT) was striking. Transplant biopsies immediately preceding OKT) therapy had shown no evidence of lymphomatous change. Re'trospective review of all transplants at our institution since the advent of OKT3 revealed an incidence of lymphoma of 2/44 (4.5%) in patients receiving OKT3 and 0/128 in nonOKT3 treated recipients. OKT3 has been reported to block cytotoxic T-cell killing of EBV_transformed B lymphocytes in vitro. OKT) may have enhanced in vivo EBF infection in our 2 patients predisposing to lymphomatous transformation. The risks of OKT) therapy must be carefully weighed in the aggressively immunosuppressed patient and further studies are required to clarify the interaction of EBV and anti T-cell antibodies in the etiology of post-transplant lymphoma •

• THE EFFECTS OF ESWL ON FUNCTION IN THE DEVELOPING KIDNEY D. E. Neal, Jr., M.D., E. Harmon, M.D., T. Hlavinka, M.D., A. Morvant, MRT, E. Richardson and R. Thomas, M.D. Tulane University School of Medicine, Delta Regional Primate Research Center, Covington, LA 70433 Extracorporeal shockwave lithotripsy has been used more frequently in the management of pediatric stones. Of concern is the possible damage to the developing kidney. We used fifteen infant rhesus monkeys ages 4-6 months. They were treated in four groups (low and high dose unilateral and low and high dose bilateral). The animals were followed with I131 hippuran scans to measure ERPF. In the unilateral groups there was a drop of ERPF in the treated kidney in the high dose group compared with a rise (consistent with renal growth) in the low dose (-3 & +1, N.S.). In the bilateral group, there was an overall loss of ERPF by 11.29, compared with a rise in cont~ols of 1.63 (p=0.028). These reEults would seem to indicate that unilat~ral treatment, in the short term, causes a dose-dependent, negligible decrease in renal function, whereas bilateral treatment causes a significant drop in overall renal function. Tle long-term followup of these animals will be presented.

o SEQUENTIAL

IMMUNOSUPPRESSIVE THERAPY OF STEROID RESISTANT FOCAL SEGMENTAL GLOMERULOSCLEROSIS (SRFSGS). Belinda Murugasu*, Susan B Conley , Jacques M Lemire*, Ronald J Portman. Univ. of Texas Med. Sch., Dept. of Pediatrics, Houston. SRFSGS is difficult to treat, has a poor prognosis and a high rate of recurrence in allografts with graft loss especially in children. We therefore devised an aggressive, sequential protocol for immunosuppressive therapy of SRFSGS . Nine nephrotic children (2-15 years) with normal renal function were treated initially with : dietary protein restriction, enalapril if hypertensive , and ~l month of prednisone (60 mg/m2) . All patients were unresponsive to oral steroids. After biopsy confirmed FSGS, pts were treated sequentially with each therapy until in remission: STAGE 1: 6 pulses of IV methylprednisolone ()O mg/kg/dose; max 1 gm); STAGE 2: chlorambucil (0.2 mg/kg/d for 8 wks); STAGE ): oral Cyclosporine (CyA) (steady state serum conc. 200 ng/ml); STAGE 4: Cytoxan (2-5 mg/kg/d PO or IV to a WBC count ~4000/mm3); STAGE 5: nephrectomy if medically necessary. Results (2-11 yr follow-up) : pulse IV steroids (n=9): 1 partial remission (PR) ; chlorambucil (n=8): 1 complete remission (CR) and 1 PR; C¥A (n=6) : 1 CR still on therapy: Cytoxan (n- 5): 1 CR; nephrectomy (n-3): 2 pts were transplanted with graft loss due to recurrence of FSGS and 1 patient is currently on dialysis. One pt died of complications unrelated to protocol. No maj or complications were seen. Sequential therapy achieved CR or PR in 5/9 pts and may be helpful for the therapy of SRFSGS. However, as there may be non-immunologic causes of FSGS, a lack of response to this protocol may be expected in some patients.

o CUNICAL AND COST EFFECTIVENESS OF ONCE

VS TIlRICE WEEKLY SUBCUTANEOUS (SC) HUMAN RECOMBINANT ERYTIlROPOIETIN (rEPO) IN CHILDREN RECEIVING CCPD. J. Ramon Ongkingco*, Edward J. Ruley, Mary Ellen Turner, Mary Rose Fragale*. Childrens Nat. Med. Centr., Dept Nephrology, Washington D.C. This study compared the clinical efficacy and cost benefit of once vs thrice weekly rEPO administered SC to children receiving CCPD. Pts who had maintained their hct at 33.±.3% on an unchanging dose given thrice weekly for 8 weeks were then changed to the total weekly dose given as a single weekly injection and followed for 8 more weeks. Hcts were measured weekly during the interdialytic period and corrected for weight variation. Dose was changed to maintain the target hct. The mean hct of 5 children (mean age = 14.9 .±. 3.2 yrs; M/F=3/2) during the thrice weekly dosing was not significantly different from that during weekly dosing (34.8.±.1.1 vs 33.5.±.1.3%). The mean rEpo dose during thrice weekly and weekly dosing was 34 .±. 1O.2u/kg and 100.9 .±. 25.9u/kg, respectively. In 2 pts, the dose was reduced during weekly dosing while 1 required a dose increase coincident with peritonitis. 2 pts who developed peritonitis during the weekly dosing appeared to have a more rapid fall in hct compared to 2 other pts with peritonitis during thrice weekly dosing although this did not reach significance. There was no difference in side effects in the 2 study periods. While once weekly dosing was clinically effective, safe, and preferred by the children and parents, weekly dosing was not cost effective based on the 2/3rds reduction in payment that results from the current Medicare reimbursement scheme.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS CHANGES IN THE DIAMElER OF INFERIOR VENA CAVA (IVC) DURING HEMODIALYSIS (HD). S. Oono*, Y. Ando*, T. Tetsuka*, K. Tabei*, and Y. Asano*. (intr. by H. Jacobson) Jichi Medical school, Dept. of Nepbrology, Tochigi, Japan. Since IVC is a high compliance vessel, its diameter, which is easily measured by B-mode echography, changes even by a small change in central venous pressure (CVP). In patients on HD, we have documented a tight cocrelation between the IVC diameter and the amount ofbody fluid, especially, circulating blood volume (CBV). In patients with deranged venous return, the correlation between those two parameters could be altered. Therefore, we compared the dynamics of IVC diameter during HD in six patients without cardio-pulmonary failure (control) and those with atrial septal defect (ASD: pulmonary arterial pressure; 44/16 mmHg, pulmon -to-s stemic blood flow rati0=2.75) or massive pericardial effu- vt~ ~1.0 sion (PE). According to the removal of body I ) ~ fluid by HD, the maximal saggital diameter of (nunlO Ivee 0.5 IVC at distal of hepatic vein junction in quiet \ expiration (IVCe) and the minimal diameter in 0 IVCi / quiet inspiration (IVCi) decreased, while col46 ~ 50 B~(Kg) lapsibility index (CI; I-IVCi/lVCe) increased 2 FIg. 1 in control. Fig.l shows a representative pat- Nee ~terns in one case. In the control, !VCe tightly (nun)1 Pre '¥. correlated with body weight (r=0.98, p
2

DOES CYCLOSPORINE (CYA) MODULATE EXTRARENAL POTASSIUM (K+) HOMEOSTASIS? Y Pei, R Richardson, W Chan*, PY Wong, A Baines. The Toronto Hospital, Toronto, Canada. CYA can cause ~yperkalemia (HIK) by impairing renal K secretion. Several organ transplant (Tx) patients (pts) who developed transient & severe HIK within 5 hours of ingestion suggested to us that it may also cause transcellular K+ shift. To test this hypothesis, 2 groups (Gr) of non-diabetic pts who fasted between 24:00-13:00 were studied. Gr A consisted of 4 renal Tx ~ts with intermittent HIK (plasma (pI) [K] up to 5.3) who were on beta-blockers. Their mean s-Cr was 150 llM. Gr B consisted of 2 healthy subjects & 2 renal Tx pts (not on CYA but on betablockers). Their mean s-Cr was 118 llM. Blood sampling was through a 3-way stopcock attached to an antecubital vein, & pI [K+] was drawn hourly from 8: 0013:00. Gr A pts were given their CYA dose after pI [KT] was drawn at 08:00. Serial pI [K+]/S on these pts are shown below: Plasma [K+] in mmol/L (mean ± SO) at 08:00 09:00 10:00 11:00 12:00 13:00 Gr A results : 4.4±.3 4.7±.3 4.9±.5 4.9±.6 4.9±.5 4.8±.4 Gr B results : 3.9±.4 3.9±.~ 3.9±.3 3.9±.3 3.9±.2 3.9±.3 Urinary K excretion collected from 8:00-13:00 was not reduced when compared to 24:00-08:00 (both standardized to a 5hour period). ThUS, CYA may modulate extra-renal K+ homeostasis; & its clinical significance needs to be further defined.

A19

.. SERUM COMPLEMENT (C) IN HEMOLYTIC UREMIC SYNDROME (HUS): A MARKER OF DISEASE ACTIVITY. CG Pan,* HE Leichter,* JC Gill,* KJ Sheth.Medical College of WI,Dept.of Pediatrics,and Blood Center of S.E. WI, Milwaukee, WI. Pathogenic mechanisms in childhood HUS include injury to the glomerular endothelial cell leading to localized intravascular coagulation. A poor clinical outcome is not readily predicted by objective criteria at onset of disease. De.pressed serum C in HUS has been described and attributed to activation by circulating immune complexes. Abnormalities in Von Willebrand factor(vWF),also observed in HUS,may be secondary to endothelial cell damage. To assess serum C as a possible predictor of clinical severity,C3 and C4 levels were measured in 33 children(age 4.9±3.9yrs)with HUS at the onset of disease. vWF activity(vWF ac) was also measured. Patients were grouped by their clinical severity as mild,moderate,or severe. Results were as follows: vWF ac C3 C4 (87-177mg/dl) Normal (lS-4Smg/ dl) (4S-200u/dl) HUS Mild(n=9) 98±36 lS.4±4.6 224±39 Moderate(n=12)103±40 13.7±S.9 210±S3 Severe(n=12) 67±22t 10±S.6tt 241±76 tp<0.02 compared to mild cases, ttp<0.04 compared to mild cases. All 3 groups showed increases in vWF ac. Mean C3' C4 levels were significantly depressed in the severe group. These data suggest C3' C4, levels may be predictors of clinical severity. Increases in vWF ac suggest the proposed mechanism of depressed C involves endothelial cell damage and intravascular coagulation leading to C activation.

.. INFLUENCE OF HLA PHENOTYPES ON THE INHIBITION OF IN VITRO ALLOREACTIVIlY BY CYCLOSPORIN A E. Pohanka", G, J. Zlabinger", B. Watschinger", O. Traindl", 5. Kudlacek", A. Hajek-Rosenmayr" and J. Kovarik" (intr. by Eli A. Friedman). Inst. of Immunology, 2nd Dept. of Medicine, Inst. of Blood Group Serology, University of Vienna, Austria. Inter-individual variations in the immunosuppressive effect of Cyclosporin A (CyA) have been observed in clinical organ transplantation. Searching for an in vitro correlate we investigated a possible relation between inhibition of alloresponsiveness by CyA and the HLA phenotypes of the responder or stimulator in mixed lymphocyte reactions. Peripheral blood mononuclear cells from 28 healthy volunteers were used as responder or stimulator cells (gamma irradiated) and the inhibitory effect of graded amounts of CyA was determined in 130 criss-cross combinations. Sensitivity of alloresponsiveness to the drug was expressed as the dose causing 50% inhibition (ED 50) and was read from the inhibition curves generated after four parameter logistic curve fitting. ED 50 ranged from 0.35 ng/rni to 33.4 ng/ml and correlated only weakly with the magnitude of the response (r = 0.12). In MLC with HLA DR4 positive responder cells, ED 50 was significantly lower (Pc = 0.0035, Kruskal Wallis) when compared to MLC with responder cells of other DR haplotypes. For HLA DRS positive responder cells ED 50 was significantly higher (Pc =0.042) when compared to DRS negative responder cells. No significant correlation between ED 50 and any particular haplotype of the stimulator cells could be observed. Sensitivity to eyA did not differ in MLC with 1 or 2 mismatches in the HLA-DR locus. In summary, we found that sensitivity of in vitro alloreactivity was different for particular HLA DR phenotypes which might have important implications for the immunosuppressive therapy of transplanted patients with Cyclosporin A.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

A20

A COMPUTERIZED INFORMATION SYSTEM IN END-STAGE RENAL DISEASE (ESRD) PATIENT CARE: DIALYSIS OUTCOMES, SEVERITY OF ILLNESS, AND STAFFING. Victor E Pollak and Anna Pesce. Dept of Med., Univ. of Cincinnati Med. Ctr. (UCMC) & Dialysis Clinic (DCIC), Cincinnati, Ohio. An on-line medical information system for nephrology was used in dialysis of ESRD patients for >12 years. The hypothesis that it would improve quality (Arch. Int. Med. 137:446, 1977) was tested by examining operations and outcomes in 753 patients starting ESRD treatment at UCMC in 1976-89. Mean unadjusted case fatality rate (deaths/year in patients receiving ~1 outpatient dialysis treatments) was 11.9% in 1980-89, vs 16.6% in Networks #17 & 9,16.0% nationwide. In 1989, it was 64% of that in Network #9. Differences were not due to case selection. Corrected for major outcome determinants age [RR, 1.035 per year), no private health insurance at ESRD start [RR 1.54), and diabetes mellitus [RR 2.04 & 1.69 for types 1 & 2), the 1989 case fatality rate was 59.6% of that in Network #9. A second hypothesis is that informed staff with complete patient information always accessible are responsible for this outcome. To analyze staff work loads, an index [SI x time on dialysis) was developed to account for illness and time of HD or PD treatment. During 3year periods from 1978-80 to 1987-89, 213, 232, 258, and 299 patients were treated by hemodialysis [HD) as outpatients, a 40% increase. Geometric mean [SI x time on HD) was 1.44, 2.05, 1.91, and 2.13 in the successive periods, a 41% increase. In 1987-89, 61% had no private health insurance, 50% were >55 years old, and 40% were diabetic. Staff concerned in patient care increased by 55%, as did staff in nursing; RNs were only 28-33% of nursing staff. Dietitian and social worker numbers were constant from 1980 onward. Nursing personnel and social workers care for a similar patient load at DCIC and in 40/48 Network #9 free-standingdialysis units surveyed. Each RN at DCIC cares for more (18.9) patients than in the Network (12.4), whereas each dietitian cares for fewer (84 vs 120). As differences in staff numbers were few, the data are consistent with the hypothesis that the medical information system played an important role in assuring quality.

HEPATITIS C IN HEMlDIALYSIS PATIENTS. C.Pru, M. Teran, * M. Ardila. * Division of Nerhrology Departrrent of M:!dicine. Centro ~dico Docente La Trinidad. Caracas, Venezuela. In order to asess the incidence of Hepatitis C (RCV) in cur hemxlialysis patients (pts.), we tested sera fran 62 pts., mo were dialyzed for 18.5 ± 26.1 SD mmths (m). The sera were tested using Hepatitis C (rDNA) Antigen Diagnostic Kit fran Abbott.

Thirteen pts. (20.9%) were positive for anti RCV (anti HCV (+», eight pts. (12.9%) were positive for anti hepatitis B core (anti HBc) and anti hepatitis B antigen surface (anti IlBAgS), a.u pts.(3.2%) were positive for anti HBc, anti IlBAgS and anti RCV. N:me were positive for hepatitis B antigen

surface. The Alanine aminotransferase (ALT) was elevated in twenty seven pts. (43.6%), ten of these pts. (37.0%) were anti HCV (+). The patterns of ALT elevations in cur 62 pts. were: Pts.

Pattern anti RCV (+) N:> elevations

2 ( 3.2%) Persistent~3 mmths 7 (11.3%) Sporadic 4 ( 6.5%)

anti HCV (-) 33 (53.2%) 6 ( 9.7%) 10 (16.1%)

Eleven pts. (84.6%) with anti RCV (+) had history of blood transfusions . Cbnclusions: 1) 1/5 of cur pts. were anti RCV (+). 2) 3% of the pts. never developed ALT elevation, but were anti HCV (+). 3) 10% of cur pts. had persistent elevation of ALT without any anti HCV (+) or active hepatitis B. 4) 1/3 of the pts. with ALT elevations were anti RCV (+). 5) Half of anti RCV(+) pts. had persistent elevation of ALT. 6) MJre than 75% of anti HCV pts. had previoos history of blood transfusions.

o

THE CANADIAN PERITONITIS REGISTRY: The results of a two year study. G.A. Posen, D. Hollomby, M. Kaye, S. Vas, G. Wu, The Canadian Peritonitis Study Group. In 1986 there was an apparent outbreak of pseudomonas peritonitis in Canada. There was concern that the organisms causing peritonitis in CAPD had changed and also become more resistant and virulent. 28 Canadian PD centres sent data by electronic mail (Envoy 100) to a central computer (at Statistics Canada) on all their patients on CAPD. All patients were registered and data collected re age, sex, catheter, water supply, living arrangements, tubing, dressing, and connectors used. In addition every episode of peritonitis was noted: the cause, organism and outcomes. Peritonitis rates were determined using patient months free of peritonitis. Data was collected for 2 years. There were 1750 patients registered, 959 male and 791 female. Organisms causing peritonitis were staph.epi. (34%), staph.aureus (13%), strep.vir. (7%), E. coli (3.5%), pseudo.aer. (3%), acinetobac.cal. (2.5%), enterococcus (2.5%), others (17.4%) and no organisms cultured (17%). Exit site infection was the cause of the peritonitis in approximately 50% of staph.aur. and pseudo.aer. Poor technique was the cause of 25% of staph.epi. and strep.vir. In the majority there was no discern able cause. The outcome was continued CAPD in over 90% of staph epi. and no organisms cultured, whereas in only 50% of pseudo. and 30% of e.coli were patients able to continue CAPD. Significant mortality only occurred in pseudo and staph.aur. The ratio of the different organisms causing peritonitis in different catheters,. tubing, dressings, water supply, age groups, and sex were similar. The peritonitis rates showed a general improvement from 1988 to 1989 (12.6 to 18.1 patients months). The comparisons of various factors influencing the rates though showed considerable variation. The organisms and their relative frequency has not changed nor have they become more resistant or virulent. The peritonitis rates overall showed improvement with time, but comparisons were difficult to interpret. A registry is not a good means to study the differences in, peritonitis rates, but is useful in looking at trends.

LACK OF RESPONSE TO PLASMAPHERESIS IN CRESCENTIC IGA NEPHROPATHY Gary M. Rabetoy, Brian R. McDonald," and Michael Charilers.* Dept. of Int. Med., Naval Hospital, San Diego, Cal itornia. Therapy with plasmapheresis for crescentic or rapidly progressive IgA nephropathy has been """loyed with mixed results. We report 3 patients with advanced, crescentic IgA nephropathy who failed to respond to aggressive therapy for th!l:ir dic!'ess, incluc!ing trectment .. ith p~G.:,.;.~~.~,f".,;,;;:.:. All three patients were male, ages 18-30, who presented with hypertension, nephrotic-range proteinuria, and advanced renal insufficiency with creatinine clearances ranging frem 9-41 ml/min. Renal biopsies were performed in all patients. The histologies in all cases revealed a crescentic glomerulopathy with varying degrees of glomerulosclerosis and interstital fibrosis, and 3+ deposition of IgA in a mesangiocapi llary pattern by illllU'lOflourescence. Treatment was begun with pulse methylprednislone followed by pred· nisone at 1 mg/kg/day, and cyclophosphamide at 2 mg/kg/day. Additionally, plaSNpheresis was done in these three patients. 4 to 8 four I iter plasma exchanges Caverage 6.3 exchanges per patient) were done over periods ranging frem 16-21 days Caverage 18.3 days). At the end of this time no appreciable improvement in renal function was observed and the phereses were discontinued. 1 patient developed sepsis secondary to a temporary vascular access for pheresis. Treatment with steroids and cytotoxics was continued for periods ranging frem 3 weeks to 2 months Caverage 31.6 days). The renal failure progressed in all three patients and they required maintenance hemodialysis for ESRD. A review of the I iterature discloses inconclusive data supporting the use of plasmapheresis in crescentic or rapidly progressive IgA nephl·opothy. In our small series of patients, there was no demonstrable benefit frem plaSNpheresis, and 1 of 3 patients sustained a ccmpl ication related to pheresis. We feel that further cl inical and h.;sto1os;!:'et crite!"i!l need to be def~r~: to FNsaibt.,identify subsets of patients with IgA nephropathy who may benefit frem plasmpheresis.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS DETECl'ION OF TRACE METALS IN PATIENrS WI'IH END

STATE RENAL DISEASE

H U Rashid,A H Khan,M H Sarker, S Akhter, F Khan Deptt.of Nephrology,IPGMR;Chemistry divn,Atomic Energy Commission and Deptt.of Pharmacy,J University Patients with end stage renal disease usually suffer from anaemia,myopathy,impotence and neuropathy. The exact cause of these symptoms are unknown.Various trace mentals including Aluminium, Zinc,Copper and Magnesium is implicated as a possible cause of these symptoms.We have studied 62 patiEtlts", with end stage renal disease over a period of one year to find out the cause of myopapathy,impotence and neuropathy of our patients.The mean age of these patients were 34±12 years(range 16-60 yrs)of which 43 were male and 19 female. Blood were collected in a specially washed non-metalic test tube for estimation of trace metals.It is noted that serum Zinc were significantly reduced with haerrxxiialysis(P
DISASTER PLANNING FOR END STAGE RENAL DISEASE (ESRD) PATIENTS. Martin Roberts, Alex J. Montez,* Phylis A. Eide,* Mark H. Barney,* Virginia M. Stephens,* Sana H. Zurayk,* David B.N.Lee. Sepulveda VA Medical Center, Los Angeles, CA. Disaster planning for ESRD patients requiring relocation to operating units after a major earthquake or other disaster may be unrealistic since all personnel may be involved with victims. Instead dialysiS should be prosponed by dietary means thereby eliminating the need for emergency arrangements. An off-the-shelf diet providing 41 gm protein, 0.5gm K, 0.3gm Na, 0.5L fluid and 1630 KCal was devised. To verify its suitability patients were placed on the diet for 1 week and 2 dialyses were skipped. Pre dialysis chemistries pre and post diet were: Predialys is BUN Creat K Na Wt (mg/dl) (mg/dl) (mEq/L) (mEq/L) (kg) Prior Diet 68 12.5 5.0 139 66 138 18.2 5.0 Post Diet 110 66 BUN and creatinine increased as expected. K, Na, and patient weight after 7 days were the same as the usual 2 day pre dialysis chemistries. Based on these results disaster planning will include 4 days on the diet yearly while skipping 1 dialysis. The need for individual dietary modification may become apparent and some patients may be unable to skip a dialysis.

A21

THE SITUATION OF CHRONIC RENAL DISEASE IN BANGLADESH. Bertram W. Roberts, Southwest Dialysis Center, San Antonio, Texas and Harrun U. Rashid,* Institute of Post Graduate Medicine and Research, Dhaka, Bangladesh. The population of Bangladesh is 110 million. The number of chronic renal failure patients is estimated to be 200,000. The most common cause of CRF is secondary infections from diarrhea and other tropical illnesses. The second most common cause is Diabetes Mellitus. There is a surprisingly high incidence of lean Type I DM. These patients have the same high incidence of complications as obese NIDDM. There are five hemodialysis machines in the entire country. ARF is treated with IPD. No other treatment regimen is available for the vast majority of patients. This abstract suggests that an international task force be instituted to help supply resources and equipment to assist in the management of these dying patients. Details of the above will be further elucidated in the presentation.

MEPERIDINE (DEMEROL) INTOXICATION TREATED BY CHARCOAL HEMOPERFUSION (CHP). Michael V. Rocco* and Ellie Kelepouris. Dept of Med, Univ of Penn, Phila PA. Meperidine is a synthetic opioid analgesic that is metabolized primarily by the liver. Several case reports describe a variety of neuropsychiatric symptoms in ESRD patients given high doses of meperidine, including convulsions and seizures. These symptoms are believed to be caused by the accumulation of normeperidine, the only active metabolite of meperidine. The removal of meperidine by hemodialysis is negligible, probably due to extensive protein binding. The elimination of normeperidine is also reduced in patients with renal insufficiency, but little is known about its clearance. To determine the effectiveness of CHP in this setting, we measured the clearances of both drugs during the treatment of a meperidine intoxicated patient. A thirty year old black male with ESRD was admitted to the hospital for abdominal pain secondary to pancreatic pseudocysts. He was begun on Meperidine for pain relief and received 1900 mg 1M ovel' the first seven days of hospitalization. On the seventh hospital day, the patient had a witnessed generalized tonic-cIonic seizure. Serum electrolytes, calcium and magnesium were normal, as were a head CT and lumbar puncture. He was treated with four hours of CHP, using a new Gambro adsorba300C cartridgeevery two hours. After therapy, the patient had no further convulsive episodes. Pretreatment serum levels of meperidine and normeperidine were 0.23 and 0.42 I'g/ml respectively: twelve hours after CHP, the levels were < 0.01 and 0.32 I'g/ml respectively. Arterial and venous meperidine and normeperidine levels were obtained during CHP in order to obtain clearance data, shown below: Time in minutes: ;N Clearance (ml/min): Meperidine 126 105 109 114 50 60 Normeperidine 105 120 90 40 50 17 We conclude that meperidine is very elTectively cleared by charcoalhemoperfusion. Normeperidine is adequately removed by CHP; analysis of the kinetic data suggests that significanttissue binding also may occur.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

A22

Verapamil TOXicity-Treatment With Charcoal Hemoperfusion (HP). Rosansky SJ, Mullenix T, Med Svc WJBD V~ Co lumbia, SC School of Medicine and Pharmacology University of SC, Columbia, SC. Verapamil (VP), a widely used calcium channel blocker is poorly removed by hemodialysis (HD). Since VP is primarily cleared by hepatic metabolism, dialysis patients do not require dose adjustment. Patients with severe liver disease; inhibition of liver metabolism or massive VP ingestion, may require extracorporeal VP removal. A patient with occult liver failure receiving 480 mg/day of VP, Cimetidine 400 mg/day (a cytochrome P450 inhibitor), developed VP /hypotens i on induced acute renal fail we. In spite of high doses of intravenous calcium, sympathomimetics and a cardiac pacemaker, the patient remained hypotensive. Combined HD (1 .2m 2 hollow fiber) and Charcoal HP (Alucart) was used to treat the toxi city. VP and NVP measured by HPLC (Smith, Kline, Beecham) declined from 687 ug /m l to 192 ug/ml and 267 ug/ml to 183 ug / ml, respectively. Clearances for VP and NVP measured, with simultaneous arterial-venous samples, hourly for five hours were: Hemoperfusion Dialysis VP 8.3 ± 3.7 ml/min 73.0 ± 13.7 ml/min NVP 13.0 ± 8.9 ml/min 54.8 ± 16.3 ml/min Although better than HD, HP relative to normal hepatic clearance is only 1/100 as efficient. Despite the five hour treatment, the patient died. Nevertheless, in patients with VP toxicity due to severe liver disease especially those receiving simultanous inhibitors of VP metabolism, prolonged HP should be considered.



DIF'FERENCES BEIWEEN Icr/V ESTIMATED BY' USING IN 'lliEX:mIT'ICAL CLEARANCE AND IN VIVO Icr/V . Lakhan K. saha,* John Van stone. Univ. of MJ,

vrrno

School of Medicine, Dialysis Clinic Incorporated, Columbia, MJ. We retrospectively analyzed data from 1936 dialysis treaboonts in 250 patients CNer a period of 2 yrs. to evaluate the accuracy of in vitro Icr/V (as estimated by the fornula Dlration of dialysis x KIXJjBody water, KIXJ=urea clearance estimated by using manufacturer's data) to in vivo Icr/V, estimated by the fornula IcrjV= -In(R0.03-uFJW». Number of dialysis treaboonts varied from 10-369 with similar blood flow (BF) & dialyzer. 'Ihe results are shown below: ~.?"'"

1'110 "'170

' " 12.11 210 Cl' CF .15.11

CF2l.08

c-ook 4000 PRIOml DiI!a:8p 140

IlF 200-299 Vl'mu Vl VU K'lVH KIf\' KI'/V 1.16 I.J "/

l.00 1.16 1.0'/ .90

1.26 l.UU

."0

.9!J .98 . ~) ! .81 • ~)J .13/

. "J . 9 2 . % • "IS .!YJ .9')

JOO-199 Vl'lID VIVO KTVH KI'/V KI'/V

400-t70

Vl'1HU V LVO K'lVH

KI'/V

KI'/V 1.16

.8l

1.1) l. JJ

1.U6

.8b

l. .l:'

l.UJ

1.21

.')(,

.%

.UJ .90 . 91

./'J .lli .8{, . '11

1.1') 1. 2 J

• ~n~

l .i~

1.61 1. 23

L1 8

1. '1.7 . ~J

1.1>: 1.22

.')~

. "16

l. ~ l

l.U~

1.12 • ~IJ

. 81

•.J~)

.i"

.ll.l

./!J

.su

. ~.2

(Blank spaces represent insufficient data; Icr'VR = ratio of in vivojvitro Icr/V). With different dialyzers & average BF ranging from 200 to 470 in vivo Icr/V varied from 71% to 99% of in vitro Icr/V. In general, the reduction in vivo 'tIT/V was greater as BF was higher. In vivo lOOaSUI"ed urea clearances during 470 dialysis treaboonts were 81-94% lower than predicted manufacturer's in vitro data. High efficiency dialyzers behaved the same way as conventional dialyzers (i.e., in vivo Icr/V & urea clearance were lower than in vitro data). Prescribing dialysis treaboont using manufacturer's in vitro generated clearances can lead to narkedly underdialysis.

4t A COMPARISON OF METHODS OF GIVING INTRAPERITONEAL

VANCOMYCIN FOR CAPD-ASSOCIATED PERITONITIS: WEEKLY LOADING DOSES VERSUS ADMINISTRATION WITH EACH CAPD EXCHANGE. M. Saddler, N. Gorban-Brennan, K. Cooper;', A. Kliger*, F. Finkelstein;; Yale University , New Haven, Ct. The optimal method of administering vancomyc i n (V) for CAPD-associated peritonitis remains controversial. The aim of this study was to assess whether weekly load ing doses of V were as effective as giving V in each exchange. Successive patients presenting with peritonitis (excluding those with gram-negative or fun gal injections) were divided into two groups: Group A received a 2g loading dose of V intra peritoneall y (IP) in 21 of dialysate. This was allowed to dwell overnight (8 to 10 hours), then qid exchanges were resumed. After one week, another overnight 2g load of V IP was given. Group B re ceived V 40 mg per 21 of dialysate in qid exchanges for two weeks. The spectrum of organisms cultured from the two groups was similar (Group A: 39% Staph. epi, 12% Staph aureus, 12% Strap sp, Group B~ 41% Staph epi, 16% Staph aureus, 6% Strap sp.). Resoluting (defined as a dialysate white cell count
o THE CAUSES OF DEATH AND CO-MORBID FACfORS

ASSOCIATED WITH PEDIATRIC DIALYSIS. M. Schwalbe·, RNeiberger·, D. Pena·, R Fennell·, A. Iravani·, G. Richard. University of Florida College of Medicine, Department of Pediatric Nephrology. Gainesville, Florida. Currently, no studies are reported which analyze the life expectancy, cause of death, or co-morbid factors associated with chronic dialySiS in children with end stage renal disease (ESRD). We conducted a retrospective chart review to determine cause of death and co· morbid factors of children undergOing chronic dialysis at the University of Florida. Distinction was made between hemodialysis and peritoneal dialysis modalities. The materials used included hospital and dialysis charts, biopsy and post-mortem reports, and death certificates. The review spanned the period January 1973 through December 1989 and included 249 children who received 5542 patient-months of chronic dialysis. Of these treatments, 3960 patientmonths were hemodialysis and 1582 patient-months were peritoneal dialysis. Twenty deaths occurred during the srudy interval, lOin the hemodialysis group and 10 in the peritoneal dialysis group. The most common immediate cause of death in these children included infection (n; 7), heart failure (n; 5) and hemorrhage (n; 5). Types of hemorrhage reported were intra-abdominal (n;2), cerebral (n;2) and pericardial (n; 1). Chronic conditions which contributed to patient morbidity but not directly to patient death included hypertension (n; 15), severe anemia (hematocrit less than 22) (n; 10), left ventricular hypertrophy (LVH) (n;8), and congestive heart failure (n; 7). We conclude that the immediate life-threatening risks to children on chronic dialysis are infection, heart failure and hemorrhage, while hypertension, anemia, congestive heart failure and LVH pose Significant threats of morbidity. Better control of these risk factors may enable the physician to improve the long term survival and quality of life for the pediatric dialysis patient.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

o llSS FREtPENI',

mlXE)~, ~ R:lJIE

MI\lN11illS H::t .>35% RR 1 YE\R IN rnF IWI'1ENIS l\I'V ~ WI.'IH IN::H:1\SID ROC &IRVIWIL C1\lSED BY zHlER). AS Sc;b..ertz*, B ~ch, SB Kahn, J Priar, E ~, I
~,m.

em :rear of wsekl.y zHlER) d::ses of 7 pts ori.ginill.y part of the Nat.icnal. 0Xp Protx:x:nl \\me evaluat:e:i far a total of 354 pt ~ (Av 51 wK/pt). Ociginal 8-12 \Ik 35% in pts with severe em' despite ~ of GFR am prcgressien to dialysis, l:ec:ause of prolcrIJErl ROC smvival clle to 1ft1Ero.

TRANSDERMAL CLONIDINE (TC) AS AN ADJUNCTIVE THERAPY IN SMOKING CESSATION IN HYPERTENSIVE (HT) PATIENTS. R. Sliman,* D. Jarjoura,* D. polste~* D. Blend,* A. Cugino,* and F. Whittier. Northeastern Ohio Univ COM, Canton, Ohio. Cigarette smoking and hypertension are both known risk factors for cardiovascular (CV) disease. Some feel that when both are present in the same patient, the risk is more than doubled. T.C. is an effective antihypertensive and has been shown in some studies to decrease systemic effects of nicotine withdrawal. We designed a placebo controlled double-blind study for smoking cessation in 40 HT patients who expressed a desire to quit smoking. The patients were randomly assigned to either a placebo or clonidine 2 mg patch and HT meds were withheld. Attempts were made at weekly intervals to maintain BP control to 140/90 or less by adding back their standard HT therapy when needed. Slightly more patients on T.C. quit smoking entirely at 4 and 8 weeks, but this result did not reach statistical significance. Patients in the T.C. group reported smoking significantly fewer cigarettes at week 8 (11.6 versus 18.2 p = 0.04). BP control was better in the T.C. group (132/85 versus 141/91, p value for diastolic BP 0.007). In conclusion, because T.C. is known to be effective as an antihypertensive, we would recommend it as the agent of choice in the HT patient who desires to quit smoking.

A23

EPIDEMIOLOGICAL DATA ON THE INCIDENCE OF END STAGE RENAL DISEASE (ESRD) DUE TO AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD). Henri E THEBAUD, Pierre SIMON, Dominique DROUET, Jean F PETIOT and the Working Party on ADPKD. Vannes and St Brieuc FRANCE. The aim of the survey was to evaluate the annual incidence rate of patients with ADPKD going into ESRD between January I, 1984 and December 31, 1988, in a region with a population of 3 million inhabitants. Informations were provided by II dialysis units. During the period under review, 92 patients (42 males and 50 females) went into ESRD at a mean age of 58.8 ± 10.7 years (range 32 - 78 yrs). M~al age at the time of diagnosis was 49.5 t 13 years (range 22 - 78 yrs). The lenght of time between the diagnosis ;l1d ':SRD was 9.2 ± 8.0 yrs (range 0.5-37.5 yrs) and no significant difference was found between males and females (7.8 ± 7.1 vs 10.1 t 9.1, ns). The age -and sex- adjusted yearly incidence rate in this region was 0.6 in 100 000 and remained unchanged during the period under review. The prevalence of ESRD due to ADPKD was evaluated to about 0.5 in 1000. Thus, considering that the prevalence of ADPKD at autopsy is about I in 500, we can estimate that only lout of 4 patients with ADPKD will go into ESRD during a normal life expectancy. We conclude that the prognosis for patients with ADPKD is better than most reports suggested some years ago.

EVALUATING THE COST EFFECTIVENESS OF EPOETIN THERAPY IN HEMODIALYSIS PATIENTS. Marilyn Slotfeldt*, Kevin Kanyo* Cintro by Richard Drake), Good Samaritan ~ospital & Medical Center, Portland, Ore. The availability of recombinant human erythropoetin, epoetin, makes it possible, without blood transfusions, to i.prove the he.atolo~ic abnor.alitie. of patients with anemia of chronic renal failure. No studies to date compare the cost of epoet;" versus blood transfusions in this pati~nt population. The purpose of this study is to evaluate the cost effectiveness of epaetin therapy. forty-four he.odialysis patients receiving epoetin therapy were studied retrospectively and prospectively. The number of units of blood r~ceived by these patients for a six month period prior to the initiation of epaetin therapy was determined by a review of blood bank records. This data was compared with the transfusion requirements and adjunct anemia therapy for a six month period after the initiation of epaetin. Cost effectiveness was measured by comparing the cost of transfusion therapy and the cost of epoetin plus adjunctiv~ anemia therapy. Although epoetin therapy reduced the tr.nsfusio~ require.ents of hemodialysis patients by 259 units; epaetin did not eliminate transfusion requirements (312 units pre epaetin, 53 unit. post epoetin). The cost of epoetin therapy exceeds blood transfusion therapy by S67,ODD,Cpre epoetin therapy cost $38,000/6 month, post epoetin therapy cost S105,000/6 months).

A24 •

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

IS IJ:J.tJ DOSE ERY'l:'HRJPOIETIN (25 units/kg) EFFOCTIVE 'IHERAPY IN UREMIC ANEMIA? J. SUssman, R. Sirota, M. Yudis, H. Stein, E. Snipes, Abington Marorial Hospi tal, Department of Medicine, Abington, PA Recanbinant human erythropoietin (rHuEpo) is effective therapy for anemia of chronic renal failure, but the optilnal dose and route of administration are unkna-m. In an open label study of safety and efficacy of rHuEpo given subcutaneously, 35 stable adult dialysis patients were randomized to a higher (75 units/kg BIW) or lower (25 units/kg BIW) dosage group for a 12 week interval. Exclusion criteria were subsequently met by 8 patients. Blood pressure, hematocrit, potassium and iron stores were measured serially. Intravenous iron dextran was administered to 10 patients who had absolute or functional iron deficiency before or during the study. In the 75 unit/kg group the mean hematocrit rose fram 24.3% to 32.6%, while in the 25 unit/kg group the mean hematocrit went fram 23.5% to 28.0%. (Mean peaks differed, p=.006 by unpaired t test.) 'Ihe first group had a faster rise with rrore patients reaching a target hematrocrit of 30% (11/14 vs. 4/13, p=.002.) Transfusion requirements dropped for both groups. 'Ihere were no episodes of uncontrolled hypertension and only 2 patients in each group required rrodification of antihypertensive therapy. A serum Kover 6. 0 was found in 3 patients fran each group. 'Ihere were no seizures, vascular thranboses or evidence of reduced dialysis efficiency in either group. SUbcutaneous rHuEpo at 75 unit/kg BIW causes the hematocrit to rise over 30% within 12 weeks while 25 units/kg BIW causes a slower rise. Because of safety, efficacy, convenience and cost, subcutanems rHuEpo is the preferred route to treat anemia of renal disease.

PROGNOSTIC FACTORS THAT FEATURE THE LONG-TERM SURVIVAL OF 260 RENAL TRANSPLANT PATIENTS IN A SINGLE CENTER. Kozo Tamura*,Michihito Okubo*, Kenichi Amemiya*,Akira Kurokawa*,Koju Kamata,Tsuneo Osakabe*,Yoshisuke Nakayama*,Mitsushi Sato*,Kazuo Kumano*,anti Tadao Endo*. Kitasato Univ. Sch. of Med. ,Depts. of Med. ,Surg. & Urol. ,Sagamihara,Japan. Two hundred and sixty consecutive patients (pts) transplanted in our institution during the past 20 yrs were retrospectively analyzed to determine the prognostic fa<:tors relevant to the long-term graft survival.Twenty-eight living-related kidney recipients fr'om one-haploidentical donors,out of the first 109 pts who were transplanted prior to 1980 and immunosuppressed with prednisolone (PSL) and azathioprine (AZ),had their graft functioned for 10 Yl'S or longer. Thei I' cl inica I and biochemical parameters at 3 mons,l,3,and 5 yr(s) posttransplant were determined and compared with those obtained from 57 control pts treated with PSL and AZ,who were also grafted one-haploidentical kidneys from living-related donors before 1980 but lost their grafts in less than 10 yrs.At none of the time periods compared, the mean PSI. dose of the long-term survivors differed from that of the control group. In contrast, the mean levels at 3 mons and 1 yr posttransplallt in BUN and serum creatinine of the long-term survivors were significantly lower than those of the control pts.Likewise,significantly higher Hb level at 3 mons and lower SGPT level at yr were observed in the long-term survivors compared with the control.None of the above parameters at 3 or 5 yrs was different between the 2 gl·OUpS. In conclusion, good renal function together with less bone marrow suppression and absence of hepatir dysfunction in the early posttransplant period may be important for the maintenance of the graft [unction for more than 10 yrs.



CLINICAL FEATIlRES OF 175 PRll1ARY VUR PATIENrS. - EVALUATION

WIlli 99mrc-IMSA RENAL SCINTIGRAPHY AND URINARY lfM MJLEClJIAR PROrEINS MASAYUKI TAKEDA, YASUSHI KATAYN1A, TAKAMI TAMURA, HTIDSHI TAKAHASHI, TOSHIKI TSUITSUI AND Sl-UfAHO SAW. DEPATRMENI' OF lJRQLCX;Y, NIIGATA UNIVERSITY SmooL OF MEDICINE, NIIG\TA, JAPAN

Fran 1973 to 1990, 175 patients with primary vesicaureteral reflux (VUR) were treated in Departm2nt of Urology, Niigata University Hospital. 113 cases were operated on and62 cases were conservatively treated. 63 cases were male and 112 were fanale. 101 cases (58%) were tmder 10 years R!d and 143 cases (83%) were under 30 years old. Fran 1980, 97I1'rc_ dinErcaptosuccinic acid (IMSA) renal scintigra{ily and rreasurerrent of 99mrc-IMSA renal uptake (IMSA uptake) were perfoIllEd in every cases. Then, high incidence of false negative findings of intravenous pyelogra{ily (IVP) revealed and grade of VUR correlated well with IMSA uptake in children, but it did not in adult. Havever, biopsy of bilateral kidneys were carried out in patient with reflux ne{ilropathy and focal glomerulosclerosis (FGS), tubular ~ were found in the region Ioktere nonnal accU!II.llation of """'rc-IMSA was seen. So, fran 1984, urinary (U) lew 1ID1ecular proteins and Uenzymes-N-acetyl ,8-0 glucosaminidase (NAG) and ,82-micraglovurin ( :M;)-were examined. U-NAG/creatinine (Cr) and U,8:M;/Cr correlated rather well with grade ot VUR, but urinary NAG/Cr and ,8:M;/Cr were high in some cases with lew grade VUR and nonnal findings of IMSA scintigra{ily. Recently, MRI has been perforned in some cases. If reflux ne{ilropathy (RN) were defined· irrpainrent f renal function or incr€ase of urinary protein excretion, 20 cases (11.4%) were classified to RN and 4 cases of RN has beCanE tmder treatrrent with henndialysis. Clinical features of RN cases will be rrentioned.

• CHANGES OF THE URINARY NAG AND /3 2-JVIG ACTIVITIES BEFORE AND AFTER THE ESWL USING EDAP LT-01, Takami Tamura. Tohru Uehara and JVIasayuki Takeda Two urinary enzymes. NAG and /3 2-JVIG were monitered in 69 patients. who had renal pelvic or calyx stone without any urinary infection and urinary stasis. Specimens were collected before and soon, 1 day, 2 weeks, 1 month and 3 months after ESWL. We obtained following conclusions. 1. NAG was excreted into the urine after the ESWL and the urinary NAG index was significantly increased owing the storage, 2. Urinary /3 2-JVIG activity was increased in 1 month and returned to baseline by 3 months. The storage does not affect urinary /3 2-JVIG activity level. 3. These findings indicate that renal tubular damage was occurred by ESWL,

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

o

LIPIDS AND RISK FACTORS FOR MORTALITY (M) IN HEHODIALYSIS (HD). D Tan*, H Zaharowitz*, S Chow*, A Antignani* , P Goldwasser* , N Mittman, P Slater, MM Avram. The Long Island College Hosp., Bklyn,NY We studied 202 lID patients from 1987 to 1990 for associations with increased M, especially cardiovascular M. Data, collected once annually when new pts would be added to the group, included age, race, gender, diabetic status, multiphasic biochemistry screen, apolipoprotein (apo) A-I, apo B, HDL-cholesterol (HDL-C), hematocrit, and ESRD history . The data of pts who survived (S) each year were compared to the pre-mortality data of those who did not survive (NS) the year. For the 3 periods studied, we observed siginificantly higher albumin (Alb) (p <.04 x 3 periods) and creatinine (Cr) (p <. Ol x 2) and tendencies to higher apo B and younger age in S than NS. The groups did not differ in other clinical and biochemical parameters including lipoprotein ratios. Nor were lipoprotein or other differences consistently seen between NS patients with and without coronary disease. After adjusting for age and months on dialysis (MOD) (both of which varied inversely with Alb and Cr), we continued to find significantly lower Alb and Cr in NS. The combination of age ~ 55 and Alb <3.6 yielded an average relative M risk of 2 . 9:1 . -In pts who survived to 1990, Cr and Alb fell significantl y over 2-3 years on HD; apo B also tended to fall . For all NS (n=55), Alb and Cr fell strikingly, but not significantly, over 1-3 years . We conclude that in chronic HD pts, significant inverse relationships exist for Alb and Cr with age, MOD and M. Alb and Cr fall over years on HD; lower values are associated with increased risk for mortality.

• HYPERCHOLESTEROLEMIA IN PATIENTS AFTER RENAL TRANSPLANTATION CAN BE AVOIDED IF CONCOMITANT STEROID DOSAGE IS LOW O.Traindl, S.Reading, E.Pohanka, J.Pidlich, J.Kovarik. 2nd Dept. of Internal Medicine, University of Vienna, Austria. (Intr.by A.I. Arieff, UCSF, CAl In a retrospective study we analyzed the total cholesterol levels in 233 kidney graft recipients treated with different immunosuppressive regimen consisting of prednisolone (pred), azathioprine (aza) and cyclosporine A (CyA). 43 patients had pred and aza (group A), 126 received pred and CyA (group B) and 64 were treated with pred, aza and CyA (group C). No significant differences in concomitant maintainance prednisolone dose, sex, age, mean graft function, mean graft survival, and proteinuria were found between these three groups. Concerning cholesterol levels, the following results were revealed: Mean cholesterol level in group A was 248 mg/dl +/-61.5, in group B 236.5 mg/dl +/-55.9 and in group C 254 mg/dl +/-71.5 (n.s.). The fact, that no significant differences in cholesterol levels between patients receiving CyA and patients with conventional therapy were found is in contrast to previously reported observations. This might be due to the fact, that our patients have a significantly lower prednisolone mainainance dosage (9.5 mg +/-5.7) than those patients reported in the literature. We conclude that CyA does not necessarily raise the serum cholesterol level when concomitant steroid dosage is low.

o ADVERSB

REACTIONS TO ISONIAZID THERAPY IN A DIALYSIS POPULATION.

A25 (INK) ~

Thienemann-Smvth*. Linda Kirlin*, Mark S. Siskind, Univ. of Arizona, Tucson, AZ. INH chemoprophylaxis for tuberculosis (TB) is indicated for all recent skin test converters, for people in close contact of patients with active disease, and individuals with positive skin tests who have additional risk factors, such as a chronic illness. In order to prevent neurotoxicity, concomitant therapy with B6 is recommended for individuals who are malnourished, alcoholics or diabetics. We report the results of INH therapy in 16 chronic dialysis patients with positive PPO skin tests after exposure to a patient with active TB. No patient had previous known exposure or history of active TB. INH therapy at 300 mg/d was started in all 16 patients. Three of the 16 (19%) developed acute neurologic symptoms within 7 days. Two hemodialysis patients developed paresthesias of the hands and feet, slurred speech, vertigo and blurred vision, and the third, a CAPO patient, experienced eNS depression followed by seizures and coma. None of these patients were diabetic, alcoholic or overtly malnourished. All symptoms resolved after discontinuing INH. INH was restarted in 2 of the 3., along with 100 mg/d of B6, and symptoms did not recur. From this experience it is clear that chronic dialysis patients requ~r~ng INH chemoprophylaxis require concomitant therapy with B6 •

RENAL FUNCTION AND MORPHOLOGY IN HEMOPHILIACS WITIi PREVIOUS GROSS HEMATURIA G. Tramonti, C. Donadio, A. Lucchetti, N. Cecconi, L. Rossi, F. Panicucci and C. Bi anchi, Unita di Nefrologia, Clini ca Medica 2, Centro Emofili a , Clinica Medica I, University of Pisa, Pisa, Italy In patients affected by hemophilia gross hematuria often occurs. Aim of this study was to evaluate renal function and morphologl' in hemophiliac patients with previous gros s hematuria. Fifty three patients (age 8 - 49 yea r s, mean 21.4) were studied. The follow i ng tests were urinalysis, mi croalbuminuria, performed : glomerular filtration rate {GFR) , effective renal plasma flow (ERPF) , renal echography, renal scintigraphy and isotopic renography . Urinalysis showed mild proteinuria (20 mg/dl) in 6 pts. Microalbuminuria, performed in 11 other cases, was normal . . GFR was less than 80 ml/min i n 16 pts (mean 67.6+7. 6 SD) and more than 80 ml/min in the remaining J7 (mean 107.92:19.0) . ERPF resulted less than 350 ml/min in 19 pts (mean 312.4+31.7) and more than 350 ml/min in 28 pts (mean- 461.12:93.5). Renal echography resulted pathological in 4 out of 31 cases, rena l scintigraphy in 8 of 51 and isotopic renography in 9 of 41 . Most of the observed abnormalities were unilateral . In conclusion a rel evant number of hemophili acs with previous gross hematuria have an evident impai rment of renal funct ion. Less f requen t1 y morphological abnormalities, geuerally unilateral, can be observed. On the basis of these res ult s follow-up of renal function and morphology in hemophiliac patient s seems necessary.

A26

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

"PSEUDO-REJECTION" CAUSED BY CYCLOSPORINE (CYA) TOXICITY IN RENAL TRANSPLANTATION (RT). Ben A. VanderWerf, Hirohisa Miwa, and James W. Williams. Good Samaritan Medical Center and Phoenix Children's Hospital, Phoenix, Arizona. "Biopsy proven" rejection is the standard for rejection post RT. 35/103 consecutive cadaveric RT treated with low dose CYA and Prednisone (P) were evaluated for a rise in serum creatinine 0-3 months post RT. Workup included ultrasound and renal scan, CYA level and renal biopsy (Bx). 4/35 patients (Pts) showed no rejection on the Bx and were considered to have CYA toxicity and were changed from CYA to Azathioprine (AZA) resulting in excellent renal function. 31/35 Pts had "biopsy proven" rejection. (One of these Pts had severe vascular rejection and was treated with OKT-3). 30 Pts were treated with daily IV Solu-Medrol, 3.5 gm. over 10 days. 25/30 Pts responded by improved renal function. 5/30 Pts did not respond to the IV Solu-Medrol therapy. Repeat Bx showed the same as the initial Bx. No further rejection treatment was given. AZA was initiated and CYA was discontinued. P was kept at 40 mg/day and tapered thereafter. These five Pts all recovered excellent long-term renal function and were considered to have .had CYA toxicity. Pts with "real" or "pseudo" rejection did not have different clinical symptoms, course, or test results. Our conclusions are: 1. CYA toxicity occurred in 9/103 CRTs. 2. 5/30 (17%) "Bx proven" rejections turned out to be CYA toxicity. 3. "Pseudo" rejection should be considered as one of the possibilities when Pts are evaluated for decreased renal function post RT, especially when rejections are resistent to Solu-Medrol therapy.

IMPROVEMENT IN SYMPTOMATOLOGY BY COGNITIVEBEHAVIORAL TREATMENT IN FLUID NONCOMPLIANT HEMODIALYSIS PATIENTS. Nand K. Wadhwa, Mark Schneider, Ronald Friend, Paul Whitaker. S.U.N.Y. Stony Brook, New York Fluid noncompliance is a major problem in hemodialysis (HD) patients. The pre$ent study was undertaken to evaluate a cognitive-behavioral treatment to reduce fluid intake and to assess symptoms related to fluid intake in HD patients with 24 session baseline interdialytic weight gains (IWG) greater than 2.0 kg. Fifteen patients were randomly assigned to either a treatment or control group. Treatment group received 8 weekly sessions of therapy focused on monitoring drinking behavior, contracting with therapists, stimulus control and positive self-talk strategies. Mean IWG was assessed at post-treatment and twelve week follow-up. The treatment group had a trend significant (p 0.06) decrease in IWG from 7.66 to 6.78 lbs at post-treatment and follow-up. Control group showed no change. The treatment group reported significant decrease in number and severity in symptoms (mean 4.57) than control group (mean 6.63 symptoms) at post-treatment (p less than .02) and follow-up (p less than .005). Data suggest that Cognitive-behavioral treatment had substantial impact on symptomatology but marginal effect on fluid reduction in HD patients.

D

'mE RELATIVE VALUE OF MEASURING A-V ACCESS

PRESSURE, BLOOD FLOW AND RECIRCULATION TO PREDICT

ACCESS THROMBOSIS. John C Van Stone, Michael Jones*, and Brenda Curtis*. Dept of Med. Univ of Missouri, Dialysis Clinics Inc. Columbia, MD. In a prospective study access pressure, access blood flow and % recirculation were measured in 171 hemodialysis accesses of 109 CHD Pta over 18 months. Access pressure was evaluated by measuring the pressure in the venous dialysis line at blood pump speed of 0, 200 ml/min and patient's routine blood flow during each dialysis. Access blood flow was measured by doppler substraction method (Keene,M-ASN Abs 18: 68A, 1985). Access flow could only be accurately determined (CV < 20%) during 63% of studies. There were 89 access thromboses. The number of thromboses with adequate data (N) I those in which the data predicted probable impending failure (F) or possible impending failure (PF) are: METHOD ACCESS PRESSURE ACCESS BLOOD FLOW RECIRCULATION

N 78

18

19

F

(%)

16 (21) 7 (39) 6 (32)

PF

(%)

19 (24) 3

(16)

3 (16)

Probable failure was predicted by at least one method in 60% of those thromboses in which data were available for all 3 methods. Measurement of access pressure with blood pump off was a better predictor then with the blood pump running. Routine measurement of access pressure may predict impending graft thrombosis in half the cases and may allow preventive intervention. Measuring graft blood flow or recirculation may be of additional help.



BLOOD PRESSURE CONTROL IN HYPERTENSIVE MEN IN MULTIPLE RISK FACTOR INTERVENTION TRIAL (MRFIT) PROTECTS THE KIDNEY. G. Walker, J. Neaton,* J. Cutler,* and R. Neuwirth* for the MRFIT Group. Johns Hopkins Univ. Sch. of Med., Baltimore, MD. Mild hypertension(HBP) as a potential cause of ESRD requir1ng dialysis was investigated in MRFIT. Of 12866 entrants, 5260 had diastolic BP(DBP) ~90 mmHg and no J;>rior Rx. fl l/Cr/ flt was a significant 1ndeJ;>endent risk factor for mortality and dec11ned during the 6+ yrs of follow-up in >1/3 of this HBP subset; 6% were <-.03 dl/mg/yr and at risk for ESRD. Risk was greater in those with entering mean arterial BP ~120 mmHg or baseline syst BP ~160 mmHg, and was greater in blacks and older men. This 6% <-.03 dl/ml/yr translates to >750,000 at high risk nationally for ESRD, an adequate source for the 10,000 new cases/yr of hypertensive nephropathy reported annually by HCFA (USRDS). Most importantly, control of DBP <95 mmH~ is assoc1ated with improving renal funct10n(+.0013±.0003 SE) and persistent DBP ~95 mmHg with progressive decline(-.0017; p<.OOl). This highly si~nificant difference persists after adJusting for age, race, DBP at entr¥ (p<.007). Rx was effective in lower1ng DBP <95 mmHg in 98% of SI participants but only 85% UC participants (p<.OOl), but fll/Cr/ fl t did not differ between SI and UC with DBP >95 mmHg although power was limited. These findings suggest that effective BP control decreases renal failure due to HBP thereby reducin~ the population of ESRD patients requir1ng dialysis, and warrant definitive testing by clinical trial.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS •

A27

DYSLIPIDEMIA IN HEMODIALYSIS PATIENTS: THE EFFECT OF SIMV AST ATIN ON LIPOPROTEINS AND REMNANT ACCUMULATION. Christoph Wanner, Claus Luley', Walter H HorI', Heinrich Wieland'. Departments of Nephrology and Clinical Chemistry, University of Freiburg, FRO. Hemodialysis (HD) patients exhibit an increased risk for cardiovascular disease. In association with the prevalence of hypertension lipid abnormalities are one of the causes of atherosclerosis in these patients. Thus, we investigated the effect of simvastatin (lOmg I't, 20mg 2 nd , 40mg 3rd month) on the lipoprotein system in 18 HD patients (serum cholesterol> 260 and triglycerides < 500 mg/ dl) during a 3 months trial. Lipoproteins were isolated by preparative ultracentrifugation. Cholesterol and triglycerides were determined by fully enzymatic methods. Plasma levels of simvastatin were measured with HPLC. Simvastatin reduced serum total cholesterol by 31.4% (295 .0 ± 12.2 vs 202.3 ± 8.9), LDL-C by 40% (181.8 ± 14.7 vs 107.4 ± 8.1) and VLDL-C by 35.2% (78.3 ± 11.1 vs 50.7 ± 8.8 mg/ dl) significantly. HDL-C (34.9 ± 2.7 vs 44.2 ± 3.5; +26.6%) and apo-Al (121.3 ± 6.0 vs 146.7 ± 8.8 mg/dl; +20.0%) increased significantly. Therefore, the ratio of LDL/ HDL-C decreased dramatically (5.9 ± 0.8 vs 2.6 ± 0.2). Serum apo-B decreased from 134.4 ± 8.2 to 84.0 ± 5.3 mg/ dl (-37.5%) but the ratio of apo-B/ cholesterol in LDL increased 0.63 ± 0.02 to 0.66 ± 0.02 (p<0.05). Triglycerides fell from 333.6 ± 42.7 to 269.9 ± 42.8 mg/ dl (-19.1%). The ratio o f trigl ycerides/ cholesterol in VLDL normalized (3.18 ± 0. 18 vs 4.05 ± 0. 18; P
• aroroXICITY IN PEDIATRIC PATIENTS RECEIVING LCNGTERM PERITONEAL DIALYSIS. B.A. Warady, L. Reed,* G. Murphy,* S. Karstetter,* U. Alon,* S. Hellerstein.* The Children's Mercy Hospital, Kansas City, MO. Aminoglycoside (AG) therapy (tx) is a risk factor for auditory and vestibular dysfunction in adults on chronic dialYSis; assessment for these complications have rarely been performed in children. 'lherefore, we evaluated 14 children on long-term peritoneal dialysis (PO) for the presence of ototoxicity secondary to AG tx. 'lhe patients (pts), age B.9±4.0 years, received dialysis for 1.S±1.3 years. Baseline evaluation of all pts and 7 controls included pure tone audianetry (PTA), tympananetry arrl auditory brainstem evoked response (ABR). Nine pts had repeat auditory testing, as well as vestibular testing with dynamic posturography, ~ 1 year later. We found the baseline auditory function of the pts to be significantly poorer than the controls at 6.0 arrl B.O (p~O.OS) kHz as per PTA, whereas the results of ABR were not different. Four pts had moderate-severe hearing loss by PTA with normal ABR testing. Three of the 4 had a history of intravenous (IV) AG tx. Repeat testing revealed no change in aUditory function, despite intraperitoneal (IP) AG tx in 5 pts between evaluations; 1 pt had a partial vestibular loss. We conclude that children receiving PO are at risk for ototoxicity associated with IV AG tx rather than IP tx. Abnormal PTA rather than ABR appears to be the best indicator of ototoxicity in this population.

DIALYZER BLOOD LOSS IS INDEPENDENT OF THE CHOICE OF MEMBRANE: POLYSULFONE VERSUS DEAE-CELLULOSE (HEMOPHAN). Richard A. Ward* and Don Duff* (intr. by G. Aronoff). Dept. Medicine, University of Louisville, Louisville, Kentucky. Dialyzer clotting results in blood loss for the patient and loss of membrane area for solute removal. We tested the hypothesis that dialyzer blood loss depends on the choice of membrane material. A pharmacokinetic model was used to cal cul ate the dose of hepari n needed to increase baseline recalcified activated clotting times by 15% during dialysis for 8 patients . The mean heparin loading dose was 8.3 ± 1.6 IU/kg and the mean infusion rate 9.3 ± 1.5 IU/kg/hr. Using these doses, residual blood volumes (RBV) and plasma thrombin-antithrombin III (TAT) levels were determined for each patient during 3 treatments with a dialyzer containing Hemophan membranes and 3 with a dialyzer containing polysulfone membranes. RBVs were measured by red cell lysis and hemoglobinometry and TAT by ELISA. The overall mean RBV was 1.9 ± 0.6 ml. There was no difference in RBV between the dialyzer containing polysulfone membranes (1.7 ± 0 . 6 ml) and the dialyzer with Hemophan membranes (2 . 0 ± 0.6 ml) (p = 0.569). However, in vitro studies suggested that rinse out of blood, post-dialysis, was faster from the dialyzer with polysulfone membranes than from the dialyzer with Hemophan membranes. Intra-dialytic plasma TAT concentrations increased to a similar extent with both membranes, averaging 29 ± 12 ~g/L compared with a pre-dialysis value of 7 ± 3 ~g/L. From these data, we conclude that dialyzer blood loss is not influenced by the choice of polysulfone or Hemophan as the dialyzer membrane.

[] ABNORMAL DIASTOLIC LEFT VENTRICULAR FUNCTION IN NORMOTENSIVE TYPE I DIABETICS WITH INCIPIENT NEPHROPATHY B Watschinger*, Ch. Brunner*, B . Ludvik*, Ch. Schnack*, R. Prager*, M. Weissel*, O.C. Burghuber*. (intr. by Eli A. Friedman) Dept. of Med. II, University of Vienna, Austria Abnormal left ventricular diast o lic function i s suggested to preceed systolic impairment in diabetic patients. As cardiac mortality in type I diabetics with nephropathy is higher than in diabetics without renal impairment, we investigated whether incipient renal change s correllate with early c a rdiac dysfuncti o n . 1 3 normo tensive type I d iabetics with inc ip ie n t nephropathy (mean age 37.8±3. 5, Diabetes d ur a tion l8.8±2.6, albumin exc r e ti o n rate > 30 mg/die), 13 type I diabetics witho ut nephro pa t hy and 13 normal controls (matched fo r age, diabetes duration and metabolic c o ntro l) were included in this study. Other diseas e s kno wn to affect left ventricular performance, suc h as co ronary artery disease e.g, were ruled out b e fore investigati o n . Parameters for left ventricular systolic ·f un c tion (assessed by M-Mode e c ho cardi o graphy ) did not differ significantly between the gro ups (Eject . fract . (%) 69 . 3±2.4 vs. 69.6±1.4 vs. 69.0±2 . 2; Fract. Short. (%) 40 . 3±2 . 2 v s . 38.5±1.1 vs. 39 . 6±1.9). Transmitral fl o w vel oc it y pr o fil es (a s sessed by Doppler echocardiography), kno wn t o be very sensitive parameter for left ventricula r diastolic function, were Sign i ficantly impaired, a~ expressed by an inversed E/A (early and late peak velocities) ratio (0.988±0.04 vs. 1.36Z±O.l (p< 0.05) vs. 1.482±O.08 (p< 0.05». Thus diabetic patients with incipient nephropathy unlike diabetics without renal impairement have an abnormal left ventricular diastolic function, indicating incipient cardio(myo)pathy.

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20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

[] RENAL OSTEODYSTROPHY IN PATIENTS ON CONTINUOS AMBULANT PERITONEAL DIALYSIS . Thomas Weinreich, Martin Zeier, Rainer Nowack, Michael Rambausek, Eberhard Ritz. University of Heidelberg, Department of Nephrology, Heidelberg, FRG.lntr.by Eli A. Friedman The influence of CAPO on progression of renal osteo-dystrophy (rOO) and the strategies for its prevention are still under discussion.

In a cross-

sectional incenter study we compared the degree of rOD and secondary hyperparathyr o idism in 15 CAPD-

patients(12m,3w,years on CAPO 3 . 5 (1-7» and 17 age matched HD-patients(8m,9w,years on HO 3.5(26» . [Cal-dialysate was 1.7mmol/l in both groups. 60\ of CAPD pat. and 27% of HO-pat. were given 1,25Vit.D3(0.25ug/d)orally.CaCo3 was given as phosphate binder and in parts or completely changed to AIOH3 in cases of hypercalcemia.pat. were investigated for (i)cortical bone mass(Barnett-index),(ii)Ca,p,Al,alk.phosphatase, 1,25Vit . D3,25Vit03,intact PTH and(iii)hand skeletal x-ray in mammography technique. Cortical bone mass was slightly higher in CAPO pat. (p
treatmeht with 1.25 ...,o1l:..D3 in the majoritY,of CAPD-

pat.Using standard [Cal-dialysate,higher dosing of 1,25Vit.D3 and CaC03 inreases the risk of hypercalcemia.Further studies have to show, wether low [Cal-dialysate and higher dosage of 1.25VitD3 and CaC03 will achieve better control of sec.hyperparathyroidism and rOD in CAPD-pat.

[] PERITONEAL DIALYSIS USING BICARBONATE-CONTAINING SOLUTION STERILIZED BY ULTRAFILTRATION. A. Yu,* M. Mohammed,* R. Soundararajan,* A. McShane,* C. Perry,* V. Gandhi,* T. Ing.* (intr. by Dennis Sloan). Hines-Loyola Medical Center, Hines, IL. Sterile peritoneal dialysis (PO) solutions containing bicarbonate, calcium, magnesium and glucose are difficult to prepare, sterilize and store. We prepared such a solution by using a "Gambro Multi Purpose System-IO" machine designed for the on-line preparation of highly purified replacement fluids for the purpose of hemofiltration through the use of multiple ultrafilters. A non-sterile bicarbonatecontaining solution geared for hemodialysis was first created in the conventional way by mixing standard "acid" and "base" concentrates with glucose-enriched, reverse osmosis-treated water. This solution was then routed through the above machine for steril·ization. The final solution had a pH of 7.1 and contained (in mmol/L): Na 139, K 2.0, Ca 1.75, Mg 0.5, HC0 3 35, acetate 4, cl 106.5 and glucose 75.6. The solution was endotoxin-free and sterile. Each of 8 end-stage renal failure patients underwent a single PO treatment using 48 L of the above solution. Pre- and post-dialysis serum samples revealed (meanzSD): BUN Creat ~ Ca ~ mg/dL mg/dL mmol/L mmol/L mmol/L Pre 21.6Z3.2 3.5ZI.2 2.0Z0.9 93Z39 10.5Z6.4 post 26.8Z3.2 4.3Z1.2 1. 7Z1. 8 56Z24 8.IZ5.6 Our patients tolerated the procedure well and none developed peritonitis. Our results suggest that bicarbonate-containing solutions prepared in this manner can be satisfactorily used to perform peritoneal dialysis.

[] RISK FACTORS FOR ALBUMINURIA IN PATIENTS WITH TYPE II DIABETES MELLITUS. T B. Wiegmann, M. MacDougall, A. Chonko, W. Moore*, University of Kansas Medical Center., Kansas City, KS . Increased excretion of albumir. is an important early marker for the presence of kidney disease in patients with type I diabetes but little is known about its prevalence and role in patients with type II diabetes mellitus. In this study we examined prospectively 224 outpatients with type II diabetes mellitus whose mix was representative of the clinic population (77% male, 23% female, 66% white, 30% black, 4% hispanic). Patients were divided by level of albumin excretion rate (AER ltg/min). Results (MeanzSE) <20(N-142) >20(N-54) >200(N=28) p(ANOVA) 5.9z0.4 68.5± 5 . 9 S35.3±9S.3 0.000 AlR Syst BP l39.9±1.7 l47.7± 3.6 l52.3± 5.4 0.01 90.l± 2.5 0.005 Diast SO. 4±1.l SO. B± 2.3 2.24±0.29 0.000 Creat 1. l2±0. OB 1. 21±0 . 04 B . 9±1. 6 N. S . Duration 7.6±0.7 9.5±1.1 5B.B±1.7 N.S. Age 60.7±0.S 60.S±1 . 4 Glucose 206. 0±6 .4 214. 3±10 . 9 213.7±15.3 N.S . GhbAlc 1l.B±0.3 l3 . B± O.S 1l.9± O.B N.S. The incidence of abnormal increases in AER (36 . 6%) with type II diabetes is similar to that reported in type I. Unlike type I diabetes, disease duration and age had no effect. Parameters of glucose control had no effect, similar to type I patients. Systolic BP rose with AER while increased diastolic BP was seen with overt proteinuria. Renal function declined progressively with AER. The study demonstrates that AER is a concurrent marker of abnormal renal function and blood pressure, rather than a predictor. The precedence between hypertension and renal dysfunction remains to be established.

C.('N'WLCNA ACUMINATUM AND VULVAR CARCINOMA - A THREAT IN THE RENAL TRANSPLANT RECIPIENT. M. Yudis, R. Sirota, H. Stein, E. Snipes, Dept. of Medicine Abington Memorial Hospital .. Anogenital (ANO) condyloma acuminatum due to the human papilloma virus (HPV) is the most common sexually transmitted disease amoung adolescents in the U.S. HPV infection has been closely related to the development of anogenital cancers. However, their potential importance in the immunosuppressed renal transplant recipient has not been well appreciated. We recently have seen 2 women with long term succ~ssful renal transplants develop vulvar cancer superimposed upon a backround of anogenital condyloma acuminatum. Both of our patients had transplants performed many years before the development of ANO. One developed it 9 years and the 2nd developed it 14 years after their respective transplants. Diffuse ANO was found. Biopsy later revealed invasive squamous cell carcinoma. Both received staged radical vulvectomy. Subsequent problems included local tumor recurrence and cellulitis and in one patient, mild transplant rejection. Our 2 cases suggest that diffuse anogenital condyloma acuminatum in the immunosuppressed renal transplant recipient may be a precursor of invasive vulvar squamous cell carinoma. The most common cancers in the transplant patient are malignant lymphoma, skin and lip cancer and cervical cancer. The best way to prevent vulvar cancer in the transplant patients is an annual pelvic exam with close observation and appropriate intermittent local therapy of the condylomata. Biopsy is often needed to exclude invasive cancer. Frequent regular gynecologic exams will increase the likelihood of detecting early carcinoma insitu and allow prompt therapy while minimizing the chances of developing invasive cancer.

20TH ANNUAL SCIENTIFIC MEETING ABSTRACTS

D THE

RENAL HEMODYNAMIC RESPONSE TO AMINOACIDS(AA) IS DIFFERENT BETWEEN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) AND GLOMERULAR DISEA.SES(GD) .If. zeier, St:.. Gebert:.h,If.Schmid,S.Zacharewics,E.Rit:.z.Dep. lfed.Univ.Heidelberg FRG(int:.r. E.A.Friedman) Adapt:.ive changes in glomerular hemodynamics are t:.hougt:. t:.o be inst:.rument:.al in causing progression of RF.In t:.his cont:.ext:. renal hemodynamic response t:.o acut:.e infusion of AA are of int:.erest:. t:.o assess acut:.e vasodilat:.ory reserve.In previous st:.udies we showed in ADPKD(in cont:.rast:. t:.o GD)t:.hat:. FSGS(marker for hyperfilt:.rat:.ion)is uncommon. This observat:.ion prompt:.ed comparison of glomerular fi It:.rat:.ion response t:.o AA in pt:.s wit:.h ADPKD and GD. We st:.udied l5pt:.s wit:.h ADPKD(med.SCrea2.5mg/dl;0.9-3.5) and 5pt:.s. wit:.h IgA-N or diabt:.ic nephr. resp. (med.S-Creal.9mg/dl; 0.9-3.5) and 9 healt:.hy probands before and aft:.er AA-infusion(75g/l2h) by inulin clearance.Prest:.udy prot:.ein ingest:.ion was monit:.ored in all,ACE-inhibit:.ors were st:.oppedprior t:.o st:.udy.AA raised Cin by lBml/min(l-56) in healt:.hy cont:.rols.AA induced acut:.e increment:. of Cin was not:. found in IgA-N/DN.Incont:.rast:. in ADPKDpt:.s. wit:.h Cin>30ml/min, Cin rose aft:.er AA by 11.6ml/min(O-56;p(.05),while an increment:. was not:. not:.ed in pt:.s wit:.h baseline GFR < 30ml/min. Conclusion:The result:.s demonst:.rat:.e differnt:. AA induced .acut:.e regulat:.ion of renal hemodynamics in ADPKD versus glomerular diseases.This observat:.ion may have implicat:.ions wit:.h respect:. t:.o mechanisms of progression •



TRIME'llIOPRIM-SULFAME11IOXAZOLE NEPHRaroxICIlY IN PATIENTS WITH AIDS. C Zumga*, A. Chua*, H. Alpert*, and C.A. Vaamonde, VAMC, Jackson Memorial Hospital, and the Dept. of Medicine, Univ. of Miami School of Medicine, Miami, Florida. The frequency and pathogenesis of trimethoprimsulfamethoxazole (T-S)-induced nephrotoxicity (NTX) are not well defined. Intravenous T-S is used as primary agent for the treatment of Pneumocystis carinii pneumonia (PCP) in patients with AIDS. We retrospectively evaluated changes in renal function in 38 patients with AIDS and PCP who were treated with T-S intravenous for at least 5 days. The dose of T-S was 19±2 (SE)/95±5 (TIS) mg/Kg/day, and was given for an average of 10±1 days (5-24). There were 33 men and 5 women; mean age was 38±2 (23-62) years. Twenty of the patients were white. Risk factors for NTX noted were voltmle depletion (21 pts), pre-existing renal dysfunction (3 pts) , and nephrotoxic agents (12 pts). In only 3 patients did serum creatinine concentration (Scr) increase >50% above baseline (B), and in 2 of the 3, other risk factors were also present (vo1tmle depletion, amphotericin B, gentamicin). Thus, in only one of 38 pts (2.6%), NTX could be attributed to T-S itself. Estimated 24 h creatinine clearance (Ccr) did not change: B 107±10; peak l> 106±1l and end of & 10l±9 mLjmin; (n=22). In the 3 patients who had elevated Scr at B, Scr decreased toward nonna1 during treatment. In 11 patients followed after ending T-S &, Scr did not change. There was no relationship between duration of treatment and change in Scr or Ccr. In conclusion, even when other predisposing factors for NTX are present, the intravenous use of T-S in patients with AIDS and PCP, carries a very low risk of toxicity. These finding are in accordance with our studies in the rat (Chua et a1).

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• IS SENSITIVITY TO CICLOSPORIN INFLUENCED BY THE HLA PHENOTYPE OF THE REOPIENT? G. J. Zlabinger", S. Kudlacek"L E. Pohanka*, M. Franz", G. Hamilton", A. Hajek-Rosenmayr" and J. Kovarik" (intr. by M. R. Garovoy). Inst. of Immunology, 2nd Dept. of Medicine, First Dept. of Surgery, Inst. of Blood Group Serology, University of Vienna, Austria. We were able to demonstrate that in vitro sensitivity of mixed lymphocyte cultures to CyA differed between individuals according to the HLA-DR phenotype of the responder. In order to evaluate whether these findings could be confirmed in vivo, CyA levels (HPLC) of kidney graft recipients during the early postoperative period were related to the HLA phenotype of the graft recipient. Within graft recipients presenting with rejection, significantly (p = 0.004) more DR2- patients (70%, 19/27) were found to have CyA levels >160 ng/mL than DR2+ patients (18%, 2/11). 33% (8/24) of DR4- patients presenting with rejections had CyA levels higher than 240ng/mL compared to 7% (1/14) of DR4+ graft recipients (p = 0.07). In contrast, GyA levels >250ng/mL were found in 40% (4/10) of the DRS+ patients but in only 14% (4/28) of the DRS· patients (p = 0.086). These clinical findings are in agreement with our results from the in vitro studies. They provide evidence that interindividual variations in the sensitivity to CyA could in part be explained by individual variables of the recipient.