Annual Scientific Meeting Abstracts

Annual Scientific Meeting Abstracts

Al\1\DAL SC [E,T] F I C ~IELl I:iC ABSTRACTS HEALTH INSURANCE COVERAGE IN 321 RENAL TRANSPLANT (TX) REX:IPIENl'S. H W Brown, M D Smith, L A Spry a...

3MB Sizes 0 Downloads 60 Views

Al\1\DAL SC [E,T] F I C

~IELl

I:iC

ABSTRACTS

HEALTH INSURANCE COVERAGE IN 321 RENAL TRANSPLANT (TX) REX:IPIENl'S. H W Brown, M D Smith, L A Spry and

TRfu'lSPLANTING FOREIGN NATIOllAL (Fill

'l11e Scientific Advisory Board, 1'<1
Turkey (10), Saudi Arabia (10), and one each from

venezuela, Lebanon, Italy, Iceland and Egypt. The pre-transplant evaluation is identical to the one used for ~aerican patients with the addition of an extensive infectious work-up to screen for diseases endemic to a particular country_ Special pretransplant problems included psychosocial, cultural, extended waiting time, inadequate medical information, financial and language barriers. Posttransplant problems included compliance, lack of follow-up, and lack of desire to return to the native country. solutions may include more education on the patient's part prior to his arrival, encouraging the use of related donors, competent interpreters and an office to assist the patient with housing and other social problems. In our program, FN patients are not given preferential treatment nor are they discriminated against. This policy has not created any problems for our American or FN patients.

<

o

DRUG ADDICTION AS A RISK FACTOR IN RENAL TRANSPLANTATION. Patricia Chinn, flartin F. Mozes, Patricia L. Barber, Raymond Pollak, Hichael ~laddux, and Olga Jonasson, Univ. of Ill. Co11. of Iled. at Chgo, Dept. of Transplant Surgery, Chicago, IL. Drug addicts, by virtue of their psychosocial and medical risk factors, have traditionally been considered "high risk" candidates for renal transplantation. We have reviewed our experience with 19 primary cadaver kidney transplants performed in patients with a history of heroin or other narcotics addiction during the period of 1978-1983 (group A). This group was compared to a matched control group from the same period (group B). The two year actual graft survival of 68% in group A compared favorably with that of 51.4% in group B (p=O.22). The current mean (+SD) duration of graft function in group A transplant 1S 43.7 + 12.8 mos. The two year actual patient survival was 84.2% in group A compared to 85.7% in the control. The incidence of clinically significant infections was not increased in group A. As expected, noncompliance (with meds and visits) was more prevalent in group A, but neither non-compliance nor the return to IV drug use with a functioninq kidney (5/19 patients) was associated with an increased graft loss. In summary, the former IV narcotic user is not at increased risk with a transplant in regards to graft or patient survival and should be regarded as an acceptable candidate for transplantation, acknowledging that noncompliance may be a problem. Heroin associated nephropathy recurring in a renal allograft is a potential risk, but has not occurred to date in any of our patients.

A PROSPECTIVE STUDY OF FOUR DIFFERENT ANTICOAGULATION STRATEGIES (AS) IN HEMODIALYSIS. R.J. CARUANA, R.M. RAJA, J.V. BUSH, M.S. KRAMER, S.J. GOLDSTEIN AND A.M. LERNER. KRAFT SOW DIVISION OF NEPHROLOGY, ALBERT EINSTEIN MEDICAL CENTER, PHILADELPHIA, PA. Eight chronic hemodialysis patients (HP) were studied during 4 dialyses to evaluate 4 different AS: systemic heparinization (SH), heparin free dialysis (HF), HF with saline flushes (200 ml every 30 min.) into the arterial line (SF), and HF with constant saline infusion (400 ml/hr) into the arterial line

(SI). All HP were dialyzed on hollow fiber kidneys (HFAK), had Hct 0('"32% and could tolerate blood flow (Qb) of 250-300 ml/min. Serum creatinine (Cr) and BUN were measured before and after each dialysis (D). Dialyzer clearance of urea (CU) and creatinine (CCr) were determined at the beginning and end of each D. Fluid weight loss (FWL), % predicted FWL and % dialyzer fiber bundle volume loss (FBVL) were measured.

PATIEilTS

C. Buszta, A.C. Novick, D.R. Steinmuller, S. streem, R.J. Cunningham and D. steinhilber. Cleveland Clinic Foundation, Cleveland, Ohio. Recent concern regarding the transplantation of FN patients has stimulated controversy regarding the ethical ana :raedical aspects of this practice. The Cleveland Clinic's reputation as an international referral center has allowed us to evaluate these patients for kidney transplant. Since January 1977, there have been 1,426 patients with end-stage renal disease evaluated inclUding 40 FN patients (2.8%). In the same period 595 transplants have been performed. There were 29 Tx in 25 FN patients (7 related and 22 cadaver donors); three patients received more than one graft. The countries represented were

There were no significant intradialytic

decrements in Cu or CCr with any AS and mean de-

crements in serum Cr and BUN were similar with all 4 AS. There were no significant differences in mean FWL, % predicted FWL or % FBVL among the 4 AS. There were no instances of clotting with any AS requiring intradialytic replacement of any part of the extracorporeal circuit.

This study suggests that HF dialysis on HFAK'S is feasible in many HP with low Hct who can tolerate high Qb' SF or S1 do not appear to be essential in HF dialysis and their elimination results in simplification of the dialysis procedure.

Al

THE IMPACT OF QUALITY ASSURANCE ON PATIENT COMPLIANCE. Cayce Cumbest, Rebecca Riskedahl, Allen Gersh, Philip Rogers. Hattiesburg Clinic Dialysis Unit, Hattiesburg, Mississippi. A study was designed to determine if a Quality Assurance (QA) Program would impact on the Social Worker's (SW) performance in a dialysis unit. The QA program evaluates specific treatment para-

SUBXIPHOID PERICARDIOSTOMY FOR SUBSTANTIAL HEMODIALYSIS-ASSOCIATED PERICARDIAL EFFUSION J.T. Daugirdas, D.J. Leehey, S. Popli, G. McCray, V.C. Gandhi, R. Pifarre, and T.S. Ing. HinesLoyola Medical Center, Hines, IL. Sixteen patients receiving maintenance hemodialysis in whom moderate to large pericardial effusions developed were treated with short-term drainage via a large-bore tube implanted into the pericardial sac under local anesthesia using a subxiphoid approach (subxiphoid pericardiostomy). In 7 patients, triamcinolone hexacetonide was instilled into the pericardial sac through the drainage tube at regular intervals. In all patients, a drainage period of 2 to 4 days, with or without non-absorbable steroid instillation, was associated with resolution of the pericardial effusion. Only one recurrence of effusion was demonstrable over a follow-up period extending from 3 months to 8 years (median 4.2 years). Complications of sub xiphoid pericardiostomy were minor (incisional hernia, wound infection, small pneumothorax) and easily treatable. Our results suggest that short-term drainage via a surgically implanted drainage tube is an effective and safe treatment of moderate to large hemodialysis-associated pericardia I effusion.

meters in a process termed "regular occurance

monitoring" (ROM). Patients are monitored by the SW each month for medication use and dialysis compliance. These data are analyzed with computerized format on a monthly basis at the QA Committee Meeting attended by a cross-section of professionals associated with the dialysis system. The QA program

monitors patients in five separate dialysis units.

Lack of dialysis compliance is defined as the number of missed treatments and arrival at the unit more

than one hour after the scheduled dialysis treatment time. This study was conducted over a 9 month

period.

The number of missed treatment visits per

month decreased from 5 missed treatments per month

to 0 missed treatments for the last month of the study. The number of late treatments decreased by an average of 50%. Evaluation of data shows that QA has not improved patient compliance with

medications.

The QA program resulted in improvement

in patient dialysis compliance.

Social problems

are complex and the long-term impact of QA requires addtional study.

EPIDEMIOLOGY OF HEMODIALYSIS (HHD).

FAILURE

ON

HOME

CHRONIC INTERSTITIAL NEPHRITIS AND MINIMAL CHANGE DISEASE: T-CELL MEDIATED LESIONS ASSOCIATED WITH FENOPROFEN CALCIUM. Douglass T. Domoto, Luis Salinas-Madrigal and Cheng C. Tsai, Departments of Internal Medicine and Pathology, St. Louis University

Barbara G. Delano, Eli A. Friedman. State University of NY, Downstate Medical Center, Brooklyn, NY. HHD offers excellent patient (pt.) survival and rehabilitation and is less expensive than center hemodialysis (CD). The initial training period for HHD is costly and involves considerable emotional commitment on the part of the patient. Those HHD pts. who "fail," especially within 12 months, not only raise the overall cost of HHD per pt. successfully trained; they themselves also experience a sense of failure. We have tried to identify retrospectively those patients at high risk for dropout due to any cause. Of 170 pts. completing HHD training in our program, 41 (24%) returned to CD: the majority of these (25) were on HHD for less than 2 yrs. With increasing time on HHD the return rate to CD declines. Black pts. (46% for men and 35% for women) were more likely to return to CD than white pts. (15% for men and 22% for women). For hispanic men and women the return rate was 22% and 17% respectively. In terms of income, "indigent" pts. (33%) returned more frequently than "middle class" pts. (20%). Patients with non-family helpers were more likely to return to CD than those helped by family members. The reasons the 41 HHD pts. returned to CD were as follows: moved out-of-state (10); problems with dialysis aides (5); medical complications (4); divorce or separation (4); removed for non-compliance (3); felt "isolated" (3); miscellaneous (12). In conclusion, in our program, white, middle class pts. with family helpers were most likely to remain on HHD. Efforts should be made to identify and support those pts. at risk of dropout especiallY the indigent black.

St. LOUiS, Missouri

Acute, but reversible, reduction in GFR, and

nephrotic syndrome correlated histologically with

acute interstitial nephritis and fusion of glomerular epithelial cell foot processes have been described with fenoprofen calcium (FC), as well as other nonsteroidal anti-inflammatory drugs.

We now report a

case of chronic interstitial nephritis with minimal change glomerular lesion associated with two years of FC use. A 66 y.o. male with rheumatoid arthritis used FC, 1200 to 2400 mg/day since 1983. In 1984, pencilla-

mine was added as well as low dose prednisone.

Nephrotic syndrome developed in May, 1985.

Serum

creatinine was 1.6 mg/dl and creatinine clearance was

65 ml/min. Twenty-four hour urine collection contained 13 gm. of protein. Renal biopsy revealed interstitial fibrosis with foci of lymphocytes. Immunofluorescence was negative.

Electron microscopy

showed extensive foot process fusion.

There was no

findings suggestive of membraneous nephropathy. Lymphocyte studies of both tissue and peripheral blood revealed a high T4/T8 lymphocyte ratio.

We conclude that chronic irreversible interstitial

changes with decreased GFR are associated with FC. This can occur insidiously. This lesion as well as the foot process fusion may be T-cell mediated as demonstrated by the elevated T4/T8 lymphocyte ratio in blood and renal tissue.

A2



OOSE-RElATED OWikJES llmJCED BY aJNl'INUOUS RENAL

NON-INVASIVE ASSESS~E~T OF SKIN IRON IN HEMODIALYSIS PATIENTS: A POSSIBLE INDEX OF TOTAL BODY IRON. r~ichael M. Friedlaender, Bella Kaufman, Dvora Rubinger, Hordecai M. Popovtzer, 'Rafi C:;orodetsky. Nephroloqy Services and De?artment of Oncology, Hadassah University Hospital, Jerusalem, Israel.

IRRADIATICN IN THE M:XJSE. R.F. Gagnon, D. Hum, E.B. Podgorsak and L. R:lsenthall. M:lntreal General Hospital, funtreal, Canada. The short-tenn effects of various radiatioo dosages 00 renal functioo were examined in 5 week old inbred C57BL/6 mice. To eliminate the intermittent nature of starrlard radiotherapy methods, radiatioo was delivered to the kidney using a continuous technique with radioactive J,ilosIhorus ( 32p) . FollONing right nefihrectat¥, the entire surface of the left kidney was covered with: 1) a polyethylene-backed 32P-irrpregnated anioo exchange resin, and 2) a silicone-=vered lead sheet to restrict the beta irradiation to the renal parenchyma. '!he doses chosen are as irrlicated below with the highest cne yielding initially - 3Od3y/min at the surface of the kidney and -2.3cGy/min at a 2rmt depth. In the control group, the same preparatioo was applied to the kidney using non radioactive P instead of 32p. Blood urea nitrogen (rrg/dL) after 10 days in groups of 7 animals each are nedians ±SD with range indicated between parentheses: Radiatioo ci:lsage None Lo.oI=l. 2 Moderate=6 High=30 22±4 25±11 21±17 47±19* (16-28) (14-46) (14-64) (30-65) *p<0.01 with all other groups Azotemia occurred in the high dose group ooly. At sacrifice, there were 00 signs of damage to any extrarenal abdcrninal structure. nus methcxi should provide a rrodel system for further studies 00 the irrpact of contioous irradiatioo 00 kidney structure and function.

Excess of iron has been described in patients underqoinq chronic hemodialysis. Hepatic and endocrine complications have been attributed to this.

The uresent study was undertaken to evaluate a noninvasive method for determination of skin iron using the technique of diaqnostic X-ray snectrometry (DXS) based on X-ray fluorescence soectornetry. 35 patients underqoing chronic hemodialysis entered the study and were compared with normal controls. Measurements were made in the forearm (dermis) and in the thenar eminence (eoidermis). The skin iron averaged 18.2+ 10.2 prom and 14.5+8.8 ppm respectively and was signific~ntly higher-than in normal controls 10.2+3.2 ppm (p


INCREASED &lSCEPI'IBILITY OF OIRJNICAILY UREMIC

Pregnancy in the Chronic Hemodialysis Patient. J Winn, R.N . Dept. of Med., Harbor-UCLA Med. Ctr., Torrance, CA. The occurrence of pregnancy, its completion to term and the delivery of a viable healthy infant is unusual in the chronic hemodialysis patient. The clinical experience with these patients has been quite limited and optimum management has not been established. Case history: a 22 year old female was admitted in the 25th week of pregnancy with a history of chronic urinary tract infections and hypertension and a serum creatinine of 5.9 and BU:-l of 69 mg/dl. An Impra graft was placed in the forearm and dialysis was initiated via subclavian catheter. Dialysis was performed five days a week for four hours, with the goal of maintaining serum creatinine < 3 and BUN <~O p,g/dl. A hollow fiber artificial kidney (Erika .7 or .8m ) was used

MICE ro INI'RAPERI'KI!IFAL CHALLEN3E WI'IH srAPHYl.()())CCUS EPIDERMIDIS. Barbara Gallirrore,

Rayroonde F. Gagnoo and Geoffrey K. Richards. funtreal General Hospital, M:lntreal, canada. An increased prevalence of serious infections in end stage renal disease patients is well documented. '!he effect of chronic uremia 01 host defense mechanisms has been investigated utilizing a IOClUse rrodel of renal failure challenged intraperitooeally (ip) with Staphylococcus e~idermidis. Groups of s~rated (S) (right kHmey electrocoagulation, left kidney mobilization) and uremic (U) (right kidney electrocoagulation, left nephrectat¥) C57BL/6 inbred mice underwent ip s. epidermidis challenge six weeks after the second surgery. Survival time was recorded and at various times after inoculation anirrals were sacrificed and their biochemical, histological and microbiological status was assessed. Within 24 hours of a 109 cfu inoculum, 100% lethality was recorded in S and U mice; hONever, survival time was less in U mice than S controls. Seventy t= hours follONing 108 cfu inoculation 66% of U mice survived corrpared to 100% survival in S controls. Of those mice surviving ooe week, specimens of parietal peritoneun and peritoneal washing fran U mice harboured greater numbers of S. epidermidis than did S =ntrols (p<0.05). Kinetw studl.es of peritoneal clearance of 106 cfu to 72 hours post inoculation demonstrated a delayed clearance from peritoneal washing and rrembrane in U mice corrpared to controls. These studies demonstrate a fundamental difference between U and mntrol mice in their response to ip S. epidermidis challenge.

with blood flow rates of 200 cc/min.

"Tight" systemic

heparinization was utilized. Bicarbonate dialysate (30 meq/l) containing 3 meq/l K+, I~O meq/l Na+ and 200 mg/dl glucose was used at a rate of 450 cc/min. Hematocrit was maintained above 3096 with transfusions. Dietary management consisted of high protein diet and therapeutic amounts of vitamins (folate, Nephrovits, and calcitriol). Fetal well-being was assessed by external fetal monitoring during each dialysis. There were occasional brief decelerations of fetal heart rate, most of which responded favorably to position change. However, there were three episodes which required early termination of dialysis. There was an increased frequency of Braxton-Hicks contractions during dialysis. of frequent Obstetrical management consisted amniocenteses and ultrasound measurements to evaluate fetal maturity. In the 35th week of pregnancy during the ~~th dialysis treatment the patient began active pre-term labor. Eight hours later she delivered a healthy 1960 gm male infant. The post partum period was uneventful. The mother was changed to twice weekly dialysis. The infant demonstrated normal growth and development (5.6 kg) at ~ months. The mother is awaiting transplantation. Conclusion: Intensive, carefully monitored dialysis, nutritional support and fetal monitoring can provide a successful pregnancy outcome in the chronic dialysis patient.

A3

BENEFITS OF A QUALITY ASSURANCE PROGRAM IN A FREESTANDING DIALYSIS FACILITY. Allen Gersh, Steve

BYPASSABLE CORONARY DISEASE IN UREMIC DIABETICS Neal Glass, Judith Orie, Folkert Belzer et. al. U. of Wisconsin Medical School, Madison Wi. This was a study of the incidence of surgical coronary artery disease (CAD) in uremic diabetics and the diagnostiC reliability of the history and thallium stress test. Twenty diabetic candidates for living donor renal transplants had routine thallium stress tests (TST) and cardiac catheterization (CAUi) that were reviewed by 2 cardiologists in blinded fashion. The history and TST were compared with CAUl to determine their reliability. Significant lesions were those occluding 50% or more of the lUmen of a coronary artery or a major branch. We did not find Significant correlation between the severity of CAD and the history or the exercise EKG. For the right, LAD, and circumflex coronary arteries, TST was correctly correlated with CATH 90%, 70%, and 75% of the time. TST was falsely negative 5%, 25%, and 15% of the time, and falsely positive 5%, 5%, and 10% of the time. Eleven patients (55%) had diseased vessels, including 5 patients with 1 vessel diseased and 1 with 2 vessels diseased, as well as 5 (25%) with 3 vessels diseased who were bypassed. Of 60 vessels examined, 22 (37%) had at least I significant lesion, and 14 were bypassed (64% of those with disease, 23% of those examined). We conclude that 1.) the history and exercise EKG are unreliable, 2.) CATH only in those with an abnormal TST would miss 10-30% of the significant lesions and 5% of the surgical patients with false negative TST, 3.) the prevalence of surgical CAD justifies an aggressive diagnostic approach in uremic diabetics unless it can be shown that their long term prognosis is not altered by CABG.

Pitts~ Philip Rogers, Jeanne Morrison. Hattiesburg Clinic Dialysis Unit, Hattiesburg, Mississippi.

The Hattiesburg Clinic Dialysis System has developed a computerized Quality Assurance (QA) Program based on regular occurance monitoring (ROM), a format for problem solving refered to as nonregular occurance monitoring (non-ROM), and task-

forcing approach.

The impact of the QA Program on

patient care and cost were evaluated. These data were then compared to the routine surveillance

technique utilized by ESRD Network-18 to determine whether dialysis units would be better served by a local QA program or by network surveillance including monitoring of mortality and morbidity data. The QA program monitored 32 factors related to dialytic therapy. Kinetic modeling was utilized heavily. The QA data was reviewed on a monthly basis by the QA Committee. This committee was composed of individuals from five dialysis units and represented a cross-section of professional talents including social worker, dietician, maintenance engineer, administrator, registered nurse and medical director.

It was felt that the local QA program better

evaluated patient care since it looked at individual

steps in dialytic therapy while the network's approach of looking at the end-point could not help

individual units solve problems or address costrelated issues. There appear to be too many demographic variations in the dialysis units surveyed by

ESRD Network-18 to allow the network to draw con-

clusions or act effectively on this data. In conclusion, a local QA program has better impact on patient care and cost than does network surveillance.

HLA IN HEROIN ASSOCIATED NEPHROPATHY (HAN). Daniel Glicklich, Lloyd Haskell. Montefiore Medical Ctr., Bronx, New York Heroin abuse has been implicated in the development of nephrotic syndrome progressing to renal failure. The most frequent histologic lesion seen in drug abusers is focal sclerosis (FS), although other histologic types have been described. HAN is seen almost excluSively in Blacks, although the reasons for this are unknown. We studied the frequency of HLA antigens in 33 Black patients (30M: 3F) with renal disease felt to be secondary to long-standing IV heroin use. 14/33 had renal biopsies: 9 had FS, 2 had membranous nephropathy, 3 had chronic glomerulonephritis. The remaining patients had nephrotic syndrome with small kidneys. HLA typing was performed using standard microlymphocytotoxicity techniques. HLA antigen frequencies in the 33 patients were compared with 3ll normal black controls using X', and p values corrected (pc) for the total number of antigens tested (60). HLA B14 was present in IS .1% of patients vs 2.9% of controls (pc <.00001) and Bw53 was present in 30.3% of patients vs 6.7% of controls (pc <.00001). In our patients the relative risk (RR) for B14 was S.9 and for BwS3 RR was 6.0 vs controls. We conclude that there may be a genetic predisposition towards developing HAN in Black IV drug abusers with Bl4 or BwS3.

INDICATIONS FOR VERY LOW DOSE CYCLOSPORIN IN· RENAL TRANSPLANTATION Duane Wombolt, Marvin Goldberg, Janyce McLin, EUltn Meiggs-Peck, Lynne Hilton Eastern Virginia Transplant Program, Norfolk Virginia Cyclosporin (CyA) has proven to be the most potent immunosuppressive agent yet available for renal transplahtation. However, its mpst troubling side effect is nephrotoxicity. We have now initiated immunosuppressive therapy with CyA in 97 patients. Most tolerate starting at 14 mg/ kg with slow taper to maintenance 6-8 mg/ kg. We have found three groups of patients who need much smaller doses. 1) A subgroup of our transplant population appears markedly sensitive to CyA requiring much smaller than previously recommended maintenance doses ranging from 1.8-3.6 mg/kg. CyA levelS as monitored by high pressure liquid chromotography (HPLC) tended to be lower in this group than others. 2)Because CyA may worsen or prolong ATN following transplantation use of low dose CyA combined with Imuran and prednisone was beneficial in 10 patierits. 3)Because of high cost and unknown long term effects of CyA elective conversion from CyA to Imuran was tried in 11 patients. This resulted in loss of 3 graft~ and rejection episoaes in 3 others. Use ot very low dose CyA from .8 -1.5 mg/kg in combination with Imuran/ prednisone allows for maintenance of graft function at low cost.

A4

~

GENTAMICIN (G) AND PHENYTOIN (P) SIEVING DURING IN VITRO CONT INUOlJS ARTER IOVENOUS HEMOF ILTRATION (CAVH). Thomas A. Golper, Abdel-Meguid A. Saad.* Ore. Hlth. Sci. Unlv., Portland, Oregon. Sieving of two prototype drugs (gentamicin, poorly protein bound and phenytoin, highly proteinbound) were measured using polysulfone capillary hemofilters in an in vitro CAVH system. Plasma water, whole plasma--a~ole blood were the solvents used during variation of drug concentration (conc.) and solvent flow rate. Our results indicate that the sieving coefficients (S) for both drugs can be accurately defined as the conc. in the filtrate divided by the conc. in the artery. This correlated (r= .98, p< .00001) with the rigorously derived Colton-Henderson expression which requires the venous conc. Sieving in the solvents followed expectations from known protein-binding properties and was independent of solvent flow rate. At higher drug conc. S increased .05 for P and .12 for G, consistent with binding site saturation. At higher drug conc. in whole blood S fell .03 for P and .07 for G consistent with compartmentalization into red cells. Although all these changes with increasing drug conc. were statistically significant (p< .05) their magnitude was so small that the clinical significance is unlikely. P sieving in plasma was doubled by the addition of free fatty acids, consistent with a displacement effect. Additional studi es reveal what appea r to be real, but sma 11 , effects of protein concentration polarization, protein-membrane and drug membrane interactions on sieving. We conclude that the major determinant of drug sieving is the extent of protein binding.

TOXOPLASMOSIS IN TWO RENAL TRANSPLANT RECIPIENTS FROM A SINGLE DONOR. ~ .G.z;.
DRUG REMJVAL DURING CDNTINIDUS HEIDFILTRATION. Peter Gwilt, Sam Yu, Donald Waters, and Kenneth Lempert. West Virginia University Medical Center, Morgantown, West Virginia. Continuous arteriovenous hemofiltration (CAVH) has became a widely accepted technique for the treatment of acute renal failure in critically ill patients. Antibiotics are cammPnly administered to such patients. However, proper dosing schedules have not been established owing to little information regarding the rate and extent of removal of these drugs across hanofiltration manbranes. We have evaluated the influence of flow rate, drug concentration, and plasma protein binding in an in vitro system using a 0.5 m2 polyacrylonitrilehelIPfil ter (Hospal SCU/CAVH). Three antibacterial agents with varying degrees of protein binding [sulfadiazine (15%), sulfamethazine (50%), sulfaethidole (95%)] were studied. Each was placed in a reservoir with varying concentrations of bovine serum albumin. Ultrafiltrate was recirculated into the reservoir to maintain steady state conditions. Degree of plasma protein binding was determined as was drug concentrations at membrane inlet, outlet, and ultrafiltrate port. Drug clearance was low for each drug indicating relatively inefficient reIIPval by CAVH. Clearance was found to increase with flow rate, decrease with extent of plasma protein binding, and remain constant with respect to unbound drug concentration. We conclude that CAVH-related drug relIPval is small and generally need not be considered in drug dosage schedules during CAVH.

VESICOURETERAL REFLUX IN A PEDIATRIC TRANSPLANT POPULATION, A CO"'ARISON OF TWO METHOOS OF URETERAL IMPLANTATION. Coral Hanevold, Jo Am Palmer, Bruce Kaiser, Martin Polinsky, Jorge Baluarte. SLChristopher's Hosp. for Children, Temple Univ. Sell .of Mod., Philadelphia, PA. Urologic complications are well recognized causes of postop morbidity in renal transplant reCipients. Although vesicoureteral reflux is one of the more common complications, the need for an antireflux procedure is not universally accepted. We evaluated the incidence of post-cp reflux in 46 pediatric transplant patients (mean age 12.7 yrs). We compared 2 types of ureteroneocystostomies, 91 extra-vesicular (EV) ron-Illtireflux procedure vs an intravesiculBr (IV) antireflux procedure. Children were routinely evaluated for reflux 6 mos postop with a voiding cystourethrogram. Eight out of 9 with EV as opposed to 8/37 with IV demonstrated reflux(X2=12.0 ,p(o.Oll. The incidence of UTI's with EV W88 1 cBse/9 pt mos; in contrast the rate with IV was I case/29 pt mos. There were no other urologic complications with EV, but I child with IV required reimplantation because of a non-reflux problem. We compared the rate of infection in all pts wi th reflux (R) to that in pts without reflux(NR), regardless of the surgical method. The incidence of infection was greatest in females with R: females-R I cBse/IO pt mos, females tofl 1 case/15 pt mos; males R I case/59 pt mos, males f\R I case/68 pt mos. Our data demonstrate that reflux frequently occurs after the EV non-antireflux procedure. Neither procedure caused frequent non-reflux urological problems,. He infection rate is higher in a child with reflux. We conclude that an antireflux procedure should be performed in females because of their increased incidence of asymptomatic bacteriuria and cystitis. Additionally we suggest consideration be given to an antireflux measure in all pediatric patients because of their need to preserve maximal renal function over a longer time period.

A5



LEFT VENTRICULAR HYPERTROPHY IN ENDSTAGE RENAL DISEASE. JD Harnett, PS Parfrey, P Barre, RD Guttmann, MH Gault. Royal Victoria Hospital, Montreal and Health Sciences Centre, St. John's. To determine (1) the prevalence of left ventricularhypertrophy (LVH=LV wall thickness> 1.1 cm) among ESRD patients and (2) the most important risk factors that independently relate to LVH 187 nondiabetic ESRD patients without LV failure in 2 hospitals had echocardiography and full clinical review. 52 of 83 (65%) hemodialysis, 18 of 20 (84%) peritoneal dialysis and 34 of 84 (52%) transplanted patients had LVH. Using multiple logistic regression the most important risk factors which independently related to LVH in the dialysis patients were age (p=.009) and high serum alkaline phosphatase (p=.03). No significant differences, comparing LVH to normal groups were observed for current blood pressure, hemoglobin, serum creatinine, functioning vascular access, weight gains between dialyses, or valvular heart disease. The mean number of hypotensive medications prescribed was significantly higher in the transplanted patients with LVH compared to those without LVH. This variable was the only predictor of LVH in the transplant patients (p=.002). To determine the relationship of ESRD therapy to LVH multiple regression was repeated using all ESRD patients (dialysis plus transplant). Now the best predictors of LVH were dialysis as current ESRD treatment (p=.OOO), followed by age (p=.008), number of blood pressure medications (p=.007), and high serum alkaline phosphatase (p=.03). It is concluded that the most important factors associated with LVH in ESRD are dialysis treatment, age, hypertension and hyperparathyroidism.

LOW GRADE ALUMINIUM TOXICITY IN CAPD. I.S.HENDERSON, A.C.T.LEUNG AND C.D.PAYTON. RENAL UNIT, ROYAL INFIRMARY, GLASGOW, SCOTLAND, U.K. Much concern has been exppessed about the role of excessive aluminium exposure in the aetiology of encephalopathy, osteodystrophy and anaemia in chronic renal failure on dialysis. The diagnostic

criteria in all cases is hyperaluminaemia ( 2umol/l). We studied a group of 6 CAPD patients who were "normo-aluminaemic" (AI 2umol/l) but satisfied the following criteria: I.Hypercalcaemia (Ca 2.50umol/I). 2.Aluminium deposition in ossification front on bone

biopsy.

3.Taking oral aluminium hydroxide.

All

patients were exposed to 4g desferrioxamine daily

administered intraperitoneally in dialysate for 3 months. Results included: I.Development of hyperalbuminaemia.

~.Rise in haemoglobin (from 7.0!

2.lg/dl to IO.5-1.8g/dl). 3.Improved symptomatology (including better sleep pattern and less restless-

ness). 4.Significant rise in serum parathormone. 5.No fall in serum calcium. We conclude that low grade aluminium toxicity in

CRF can only be diagnosed by bone biopsy and that gratifying response to treatment may be achieved with

ANTIHYPERTENSIVE AND RENAL EFFECTS OF ENALAPRIL IN POST-TRANSPLANT HYPERTENSION. Donald E. Hricik. Case Western Reserve Univ., Dept. of Med., Cleveland, Ohio Acute renal failure (ARF) may complicate therapy with angiotensin converting enzyme inhibitors in patients with transplant renal-artery stenosis (TRAS). To determine the incidence of ARF and its correlation with underlying TRAS, the renal effects of enalapril were studied in 10 hypertensive transplant recipients. Blood pressure (BP), inulin and PAH clearance were measured before and after a "test dose" (10 to 20 mg) of enalapril. The dose was then doubled at weekly intervals until BP was <140/90 mm Hg or to a maximum dose of 80 mg/day. A diuretic was added if BP remained ;;>140/90 mm Hg on the maximum dose. The test dose had no significant effect on inulin or PAH clearance but significantly lowered systolic and diastolic BP, an effect enhanced by increasing the dose of the drug and/or addition of diuretics during chronic therapy: BP (mm Hg) ± SEM (Systolic/Diastolic) Baseline After Test Dose End of Study 173.5±5.0 l5B.5±7.5 (p30% rise in serum creatinine concentration) during chronic therapy. In 3 of 4 patients, ARF was temporally associated with the addition of a diuretic. Angiography revealed >50% TRAS in 3 of 4 patients with ARF. It is concluded that enalapril alone or in combination with a diuretic is effective in lowering BP in hypertensive transplant recipients. ARF during enalapril therapy should raise the suspicion of TRAS. Diuretics may enhance the risk of enalapril-induced ARF. The acute BP or renal response to a "test dose" of enalapril does not predict the development of ARF at higher doses.

intraperi~oneal

desferrioxamine.

THE IMMUNOGENICITY OF HEPATITIS B VACCINE (HEPTAVAX) IN CHRONIC, AMBULATORY PERITONEAL DIALYSIS PATIENTS (CAPO). Fred E. Husserl, W. Perry Stokes, Jr., and Luis A. Balart, Ochsner Clinic and Alton Ochsner Med. Fdn., New Orleans, LA. The ability of hepatitis B vaccine to raise protective antibody levels in hemodialized chronic renal failure patients ranges from 50% to 75%. The immunogenicity of Heptavax was evaluated in CAPO patients. Ten healthy volunteers received 20..ug at 0, 3, and 6 months. CAPO patients (2I) received 40Alg at similar intervals, using identical vaccine lot. Participants were HBSAg, HBSAb and HBCAb negative at onset. Vaccine was given in the buttock to CAPO patients and in deltoid to controls. AL T, HBSAg, HBSAb and HBCAb were checked at 0, 3, 6, 9, and 12 months. Protective antibody response was defined as HBSAb titer > 10 SIN units (ratio of sample counts/ minute to countsTminute in negative control) on 2 sequential samples. One CAPO patient had a non-A, non-B event after transfusion; none had hepatitis B events. All controls and 7 of 21 CAPO patients (33%) developed protective HBSAb (p
A6

EFFICACY AND SAFETY OF PHOSPHATE (P04) BINDING WITH MAGNESIUM CONTAINING ANTACIDS (MGA) AND MAGNESIUM FREE DIALYSATE (MGFD). Paul G. Jenkins, David Resnick, Robert Wurm. Univ. of L~isconsin ~led. Sch., and Mount Sinai Med. Ctr., Milwaukee, Wisconsin. Increased concern has developed about aluminum toxicity resulting from chronic use of aluminum antacids (ALA) in chronic dialysis patients. The MGA Maalox was used in 3 patients on chronic hemodialysis in place of ALA in conjunction with MGFD. ALA and standard magnesium dialysate (MGD), with 1.5 mEq/L of magnesium were used for 2 weeks followed by 4 weeks of MGA and MGFD, then 2 weeks of MGA and MGD. Dialysate calcium was 3.5 mEq/L. Pre and post dialysis calcium (Ca), magnesium (Mg) and P04 were measured at each mid week with the following results: Mean Mean P04 mg% M9 mEg/L Pre Pre Post '" ALA/MGD 4.84 2.90 2.74 -0.26 MGA/MGFD 4.28 3.27 1.93 -1.34 MGA/MGD 5.60 4.05 3.33 -0.72 ,Je conclude that over a short term, use of MGA in conjunction with ~lGFD can effectively control serum P04 levels without unsafe elevations of serum MG levels. Stool softening agents were not required during the period of MGA as constipation was not a problem. Use of llGA can decrease the aluminum load given to patients. Long term efficacy and safety is unknown. The effect of a pure ~lGA is unknown.



OF CEFOPERAZONE (Cef)/SULBACTAM (SuI) IN CAPD PATIENTS. C.A. Johnson, S.Ii. Zimmerman, D.P. Reit0erg. T.J. Whall, W.A. erais, Univ. of WI, Madison, WI, Pfizer Inc., New York, NY. The combination of SuI, a beta-lactamase inhibitor, and Cef resul ts in an extended spectrum of antibacterial activity. SuI is renally eliminated and Cef nonrena 11 y, so it is important to determi ne the pharmacokinetic profile of this fixed combination in patients undergoins CAPO. Six non-infected patients were given, in a randomized cross-over fashion, a fixed dose of Cef (2gm) and SuI (19m) either IV or IP. Simultaneous blood and dialysate samples were obtained over 48 h. All uri ne \'Ias coli ected. Dialysate was exchanged every 6 h. Jrug levels were determined by HPLC. Peak serum levels of IV Cef were 280.9 "g/ml; peak serum level s of IP Cef were 38.9 ~s/ml and occurred 2 to 4 h post-dose. Peak serum levels of IV SuI were 82.2 ~~/ml; peak serum levels of IP SuI were 24.4 pg/ml and occurred at 6 h. Comparison of area under the curve (IP vs IV) revealed 60% of the IP Cef dose and 70% of the I P Su 1 dose was absorbed. Followin~ the IV dose, dialysate Cef levels were potenti ally therapeuti c for most CAPD-peritoni ti s pathogens by 15 min. Following the IP and IV doses serum Cef levels were potentially therapeutic for 12 h. Serum and ciialysate clearances of Cef I'Jere 71.9 and 0.6 mllmin respectively; of SuI, 33.4 and 3.6 r.;l/min. Renal clearance of Cef \'las < 1 ml/min; for SuI, < 5 ml/min. Steudy-state volume of dist. of Cef l'las 12.8 L; for SuI, 20.2 L. Serum t~ of Cef Vias about 2 h; of SuI, 6.5 h. ESRD and CAPO do not alter Cef pharmacokinetics so dose adjustment is unnecessary. SuI doses may need to be reduced in CAPO patients.

THE ERYTHROCYTE SEDIMENTATION RATE (ESR) IN PATIENTS WITH END-STAGE RENAl DISEASE (ESRD). Jens, P, Bathon,

P~ARMACOKINETICS

J, Graves, J, Mayes, M. West Virginia School of Med., Morgantown, WV. The ESR is a commonly used marker of inflammation

and infection but its clinical usefulness in patients

with ESRD has not been previously evaluated. We prospectively evaluated 60 stable ESRD patients (48 incenter hemodialysis. 4 home-hemo and 8 CAPD) to check the incidence of elevated ESR (Westergren method) in this population. ESR was also measured immediately pre and post hemodialysis in all in-center hemodialysis patients to evaluate the acute effects of a di-

alysis treatment on ESR. ESR was normal (0-23 mm/hr) in a 4 (7%), mildly elevated (25-40) in 9 (15%), moderately elevated (41-60) in 13 (22%) and markedly elevated (>60) in 34 (57%) of patients. 12 (20%) of the patients with ESRD had ESR > 100 mm/hr. In a linear models analysis, only increasing age (p<.02), decreasing hematocrit (p<.Ol) and decreasing serum calcium

(p<.OOOl) correlated significantly with elevations of

ESR.

PROGNOSTIC IMPORTANCE OF GLOMERULAR C1q IN IDIOPATHIC NEPHROTIC SYNDROME DUE TO MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS. J. Charles Jennette & Cecilia G. Hipp, U~.C. Sch. Med., Dept. Pathol., Chapel Hill, NC. We have recently described a clinically and pathologically distinctive glomerulopathy designated C1q nephropathy (C1qN) (Am. J. Kid. Dis. 6:103,1985). C1qN typically produces nephrotic syndrome (NS) in older children and young adults, and is characterized pathologically by predominantly mesangial glomerular C1q intense immunostaining. To determine the prognostic significance of intense C1q immunostaining, the clinical courses of 15 patients with C1qN were compared to 13 age-matched nephrotic patients with similar lesions by light microscopy but less than 3+ C1q. The data for C1qN and non-C1qN patients were, respectively: 23 & 22 mean follow-up months, 13% (2/15) & 69% (9/13) resolution of proteinuria, 54% (7/13) & 77% (10/13) amelioration of NS, and 33% (5/15) & 8% (1/13) development of renal insufficiency (Cr>1.5mg/dl). With prednisone therapy, the data for C1qN and non-C1qN patients were, respectively: 11% (1/9) & 73% (8/11) resolution of proteinuria, and 67% (6/7) & 82% (9/11) amelioration of NS. These data show, after an average 2 years follow-up, patients with intense C1q immunostaining have over 5 times more persistence of proteinuria, and 4 times more progression to renal failure than age- and light microscopic lesion-matched nephrotic patients.

Despite known correlations of age and sex with

elevated ESR, the magnitude of ESR elevations in this group could not be explained solely by these parameters. The etiology of ESRD, type of dialysis membrane, duration of dialysis, mean midweek BUN nor type of dialysis correlated with elevations in the ESR. Pre-dialysis ESR (N=48) was 69±4.4. post-dialysis ESR was 72±4.8 (pN.S.). We conclude that most patients (93%) with ESRD will have an elevated ESR and therefore the ESR has little utility as a marker of other illnesses. The etiology of the evaluations of ESR and ESRD patients is unexplained but is not related to the type of dialysis, cause ef ESRD, or a single dialysis membrane interaction.

A7

CAPTOPRIL TEST FOR RENOVASCULAR HYPERTENSION Surinder Kad, M.D., Department of Internal Medicine, S.U.N.Y., Upstate Medical Center, Syracuse, New York. 62 year old male, hypertensive for 15 years, on Thaizide, Apresoline, Aldomet, Tenormin, and Potassium chloride, with blood pressure lSO/90 to 210/110 mmHg, was evaluated for uncontrolled hypertension. Serum creatinine was 1.S mg/dl and Renal Flow Scan done one year ago was normal. Captopril was started. Within one week, blood pressure was 170/S0 mmHg, but serum creatinine rose to 4.2 mg/dl. Abdominal bruit was audible on left side. Renal Sonogram showed a small right kidney with reduced cortical thickness. Renal Flow Scan showed right renal ischemia. Renal Angiogram showed bilateral renal artery stenosis, 99% on right side and 90% on left side. Plasma Renin Activity was non lateralizing. Inferior Mesenteric Artery and Left Common Iliac Artery were also occluded with diffuse plaquing in abdominal aorta. Captopril inhibits Angiotensin converting Enzyme, (ACE), and there is decreased production of Angiotensin II (vasoconstrictor). ACE is also known to degrade Bradykinin (vasodilator). Captopril test is very sensitive for Renovascular hypertension. In Renal Artery Stenosis, adaptive intrarenal mechanisms to support Glomerular Filtration Rate (GFR) are dependent on vasoconstriction of postglomerular efferent arteriole by Angiotensin II. Captopril obviates this protective adaptation and may result in considerable fall in GFR which is reversible on discontinuation of Captopril. Renal Angiogram is the ultimate test for evaluation of Renal Artery Stenosis. Renal Flow Scan lacks sensitivity.



A COMPARATIVE STUDY OF AMBULATORY PERITONEAL DIALYSIS MODALITIES. Stephen M. Korbet, Catherine Firanek, and Edmund J. Lewis. Rush Medical College, Chicago, IL. 60612 Sixty-four pts (35 black/29 White) have been tra i ned for ambul atory PD with a total of 964 pt months experience (mean 14.3,range 1-42 months). Fourteen (10 black/4 White) pts were diabetic. We have used the Disconnect System (DS) in 37 pts, CCPD in 14 pts and the Standard Closed System (CS) PD in 23 pts. Diabetic pts comprised 13.5% of OS, 14.3% of CCPD and 30.4% of CS pts. Pts were preferentially placed on OS or CCPD. The mean age for all pts was 48 yrs (range 10-79) and 54 yrs (range 31-74) for diabetic pts. Pts on the OS were similar to CCPO pts with respect to age but were significantly (PeO.05) younger .(41.1±15 vs 54.1±18 (SD) yrs) than CS pts. The mean level of education was 12.6 yrs (range 3-19 yrs) for all pts and 11.7 yrs (range 3-18) for diabetic pts. Pts on the OS had a similar level of education as CCPD but h ad significantly (PeO.05) more education than CS pts (13.2±3 vs 11.3±3 (SO) yrs). Our total incidence of peritonitis was 1.7 episodes/pt-yr. The incidence of peritonitis episodes/pt-yr was 1.7 for OS, 0.5 for CCPD and 2.8 for CS pts. The incidence of peritonitis for each modality was similar for diabetic pts. The 2 year survival for all pts was 81.1% by life table analysis. Diabetic pts had a 2 yr survival of 62.1%. The OS and CCPD pts had 2 yr survivals of 83% and 100%, while CS pts had a 1.5 yr survival of 58.8%. In our experience: 1) The incidence of peritonitis is unrelated to the number of disconnections involved with a PO modality. 2) Diabetic pts are at no greater risk for peritonitis than non-diabetic pts irrespective of the PD modality.



RENAL

l!lSEASE

IN

PATIENTS

WITH

MASSIVE

OBESITY.

B.L. Kasiske and J.T. Crosson, Dept. of Med. and Path., Henn. Co. Med. Ctr., U of Minn., Mpls., MN. It is unclear whether renal disease in patients with massive obesity is different than that

which occurs in individuals who are not obese. We reviewed relial biopsy records spanning four years and found 17 patients biopsied for marked proteinuria. Each weighed more than 165% ideal and had no clinically apparent systemic disease. Clinical information and biopsy results were compared to 34 normal body weight controls matched for age, sex, and similar clinical presentations. Histopathologic changes characteristic of focal glomerulosclerosis were found in 9(53%) of the obese patients compared to 2 (6%) of the controls (pO.05). Cholesterol and triglyceride levels were not significantly different between obese patients and controls. Serum albumin, however, was higher in obese patients than in controls (3.5±O.2 vs. 2.5±O.1 g/ dL, p
A8

THE OUTCOME OF THE CYCLOSPORIN TREATED CADAVERIC RENAL TRANSPLANT RECIPIENT WITH PROLONGED INITIAL NON FUNCTION. Martin A. Koyle, Jacob Rajfer, Richard J. Glassock, and Harry J. Ward. Renal Transplant Section, Harbor-UCLA Medical Center,Torrance, CA The administration of cyclosporin (CYS) in the immediate perioperative period has been associated with an increased incidence of delayed initial graft function. Attempting to distinguish between acute tubular necrosis (A TN}, acute rejection, and CYS nephrotoxicity during this period of non function can be a diagnostic dilemma. Of 53 consecutive cadaveric renal transplants performed over the past 20 months using CYS and prednisone (P) immunosuppression, 11 (21%) experienced nonfunction for > 14 days, i.e. prolonged initial non function (PIN F). All of these patients were managed by rapidly tapering their CYS doses while 7 of them addi tionally were converted to a three drug regimen of low dose CYS, P, and azathioprine (AZA) or to a AZA/P only protocol. Seven of the 11 grafts began to function within 3-63 days of CYS tapering. The mean three month serum creatinine in this group is 1.8 mg%. Despite excellent perfusion on radionucleide scans, the absence of histological rejection on biopsy, and conversion to AZA/P, four patients, followed > 3 months, continue to require dialysis. This group (primary non function) constitutes the largest cause of graft loss in our series (4/7 graft losses). Experience with immunosuppressive protocols involving low dose CYS or those implementing CYS only after graft function is evident, is necessary in an attempt to decrease the incidence of PINF and primary non function.

CREATININE KINASE (CK) ELEVATIONS IN CAPD AND HD PATIENTS. Sunder Lal, Karl Nolph, Hannelore Hain, Harold Moore. Univ. of I~O, VA Hosp., Dalton Res. Cent., Columbia, MO. Serum creatinine kinase (CK) '·IB fraction (CK-r,lB) is considered a sensitive indicator of acute myocardial infarction. The prevalance of total CK and isoenzyme elevation in patients on CAPD or HD remains controversial. We studied 105 patients, 53 on CAPD and 52 on HD. The mean age of the CAPD patient population was 55.7 ! 1.8 SEN (range 25-77) years and of HD patients was 55.3 ! 2.2 (range 22-84) years. The mean duration of CAPD was 23.5 + 2.5 (4-87) months, of HD 40.1 + 4 (range 5-132) months. Patients with a history of chest pain or cerebrovascular accidents in the past 6 months were excl uded. None had symptoms of myopathy. All HD patients routinely receive a weekly If.l decadurabolin injection. 8100d for CK in these patients was drawn on the third day following injections. Total CK was measured by At1P modified U.V. methodology, and CK-~18 isoenzyme by an e 1ectrophoreti c method. CAPD HD 7/53 (13.2%) 22/52 (41. 5%) tTotal CK 1/53 ( 1. 9%) 6/52 (11.3%) 1- CK- MB

*

EFFECT OF MOLECULAR WEIGHT (MW) AND PROTEIN-BINDING (PB) ON DRUG REMOVAL BY CAVH. Alan Lau, Nouhad Kronfol, Jose Colon-Rivera, and Claudia Libertin. Depts. of Pharmacy Practice and Medicine, University of Illinois at Chicago, Chicago, Illinois. The CAVH hemofilter membrane has large pore diameter which allows efficient removal of plasma water and solutes with MWs . .: : IO,DOO D. In contrast, traditional hemodialysis (HD) membrane effectively removes only solutes with MWs <: 500 D. Commonly used drugs, often with MWs up to 2,000 D, are therefore expected to be filtered and removed efficiently through ultrafiltration (UF) during CAVH. The removal of 5 drugs by CAVH was evaluated in vitro using bovine blood perfused through a polysulfone membrane (Ami con Diaf il ter-20) • Sieving coefficients (SC) and clearances (Cl) were

calculated

according

to

arterial,

venous

and

ultrafiltrate drug concentrations. Drug MW %PB SC* Cl* Theophylline 180 55-65 1.04+0.03 20.54+0.57 Phenytoin 252 80-90 0.15+0.03 2.27+1.03 Tobramycin 467 0-10 0.69~0.07 14.38+2.23 Digoxin 781 20-30 0.31+0.06 5.35+0.97 Vancomycin 1800 45-55 0.33+0.06 7.07+1.47 *At blood and UF flow of 100 & 20ml!min respectively.

Our results suggest that total CK is often elevated in dialysis populations. Both total CK and CK-MB were more frequently elevated in HD patients. The CK elevations may be due to (1) the presence of subclinical myopathy (2) regenerating muscles or (3) the effect of intramuscular injection. The range of CK t,18 isoenzyme elevation was 5 to 8% without clinical evidence of myocardial infarction.

Both the SC and Cl become smaller wi th increasing MWs, except for phenytoin, whose reduced SC and Cl are consistent with its high %PB. Compared with HD, CAVH may remove a larger amount of low PB drugs with MWs between 500-10,000 0 (eg. digoxin, vancomycin). The effect of this increased Cl is further amplified by the longer CAVH treatment time. Dosage modification may thus be needed in these patients.

ABILITY OF PATIENTS OF WHO HAVE HAD PREVIOUS CAPTOPRIL-INDUCED AGRANULOCYTOSIS TO TOLERATE Et~ALAPRIL. Michael C. Laver, Paul E. de Jong, John Russell, Robert W. Taylor and E. Paul Mac Carthy. Hypertension Program, University of Cincinnati Med. Ctr., Cincinnati, OH. Angiotensin converting enzyme inhibition has assumed a very important role in the treatment of hypertension particularly when hypertension is severe and often in conjunction with renal failure or connective tissue diseases. Unfortunately, the frequency of bone marrow depression due to Captopril is increased markedly in the presence of these two additional factors. Enalapril was developed without a sulfhydryl moiety to render it less likely than Captopril to induce bone marrow depression and other adverse events. We reported four patients who had clearly Captopril related episodes of agranulocytosis three of whom had connective tissue disease and impaired renal function. After recovering from their episode they have been treated for periods of five to 26 months with Enalapril with both good control of their blood pressure and no evidence of marrow toxi city. We sugges t tha t Ena 1apri 1 is a preferable drug to use in the presence of these risk factors for leukopenia.

CREATININE CLEARANCE AND 1 YlAR GRAFT SURVIVAL: A COMPARISON OF CYCLDSPORINE VS. CONVENTIONAL THERAPY IN A PEDIATRIC RENAL TRANSPLANT CENTER. Stephen Lawless, Bruce Kaiser, Bruce Morgenstern, Martin Polinsky, Charles Wagner, H.Jorge Baluarte. St.Christopher's Hosp.for Children.Temple Univ.Sch.of Med., Philadelphia, PA. Cyclosporine A(CyA) is being used more frequently for renal transplantation. One of its potential drawbacks is nephrotoxicity. Since 1978, ~ have adopted a criteria for first cadaver transplants of using a 2 or greater HLA Antigen (Ag) match in children with ~5 blood transfusions. These children receive conventional therapy (prednisone, Imuran). eyA has been used with prednisone since 1983 for third or fourth transplants, second transplant after ATG failure, waiting on the cadaver list >1 year, or cytotoxic antibody titers >80~. We reviewed the survival and creatinine clearance of all cadaveric transplants who had received ~5 transfusions, comparing children with 0 and I Ag matches, and 2 Ag matches on conventional therapy, to those receiving CyA. Using life table analysis, the 6 and 12 month graft survivals are as follows: o and I Ag(n=26) 57~, 53%; 2Ag(n=40) 76~, 74~; and eyA treated (n=14) 68%, 68%. Since survival curves were not significant ly different we compared the mean calculated creatinine clearance at 6 months for the children receiving conventional therapy to those receiving CyA: conventional (n=41) 80mI/min/i. 73m 2 vs CyA (n=8) 60 ml/min/I. 73m 2 (O.OS
A9

o

EFFEX:::TS OF DIETARY FISH OIL ON SERUM LIPIDS AND BlLOD COAGULATION IN PERI1WEAL DIALYSIS PATIENTS.

Kenneth Lempert, John Rogers, and Margaret Albrink. West Virginia University Medical Center, Morgantown, West Virginia. Hyperlipidemia has frequently been reported in patients treated by continuous ambulatory peritoneal dialysis (CAPD) and may contribute to accelerated atherosclerosis. The ingestion of fish oil rich in eicosapentaenoic acid (EPA) has been shown to lower concentrations of triglycerides (TGs) in hemodialysis patients and normal subjects, but can adversely effect blood coagulation. The effects of a daily fish oil supplement rich in EPA were studied in 11 stable adult non-diabetic CAPD patients. Serum lipids, platelet aggregation studies, and template bleeding times (TBTs) were determined before and after 4 weeks of fish oil treatment. Serum TGs decreased from 297 ± 140 to 211 ± 95 mg/dl (p < 0.01). High-density lipoprotein (HDL) cholesterol fell from 45 ± 10 to 41 ± 10 mg/dl (p< 0.025), and low-density lipoprotein (LDL) cholesterol increased from 172 ± 53 to 208 ± 63 mg/dl (p< 0.01). Total cholesterol was unchanged. No significant change occurred in TBT, platelet count, hematocrit, or platelet aggregation response. Clinically inportant uremic bleeding was not apparent. We conclude that in CAPD patients an EPA-rich fish oil supplement favorably effects peritoneal dialysisrelated hypertriglyceridemia and can be ingested without promoting uremic bleeding. The likely beneficial impact on atherogenesis resulting from the lowering of TGs may be mitigated by concomitant changes in HDL and LDL cholesterol.

*

EA'ZLY ~XPSRIr::lCL WITn CO:-JTINUOUS ARTERIOVE:-JOUS HEMOfILTRATIO:, (CAVil) I:l IN?;)!TS AND CHILD:li:N. MR Leone, SR Alexander, RD Jenkins, TA Golper, Dept. of !='ediatrics and Med., Oregon I-llth Sci Univ, Portland, OR.

We have employed CAVH in 3 infants and 2 children suffering catast~ophic medical illness. Ages ranged from 12 days to 4 yrs, Heights from 2.5 to 18 kg. In the two youngest patients, we used the Amicon minifilter, but due to low ultrafcltration rates (UFR <1.5 cc/kg/hr) this filter .as abandoned in subsequent patients in favor of the Amicon diafilter-20. Standard blood lines were shortened to reduce the extracorporeal vol to ~ 27cc. In a 6 kg infant changing from the minifilter to the diafilter-20 improved blood flow and U~R witllout changing access or cardiovascular status. Our experience in the most recentlytreated ?t. might serve as a prototype. This 9 mo. old 6 kg infant received CAV:tl for 63 hI'S in a setting of septic shock, DIe, anuria, and hypotension (sys B? 50-70 mm Hg on epinenephrine and dopamine). Blood and plasma flo," rates averaged 79 & 51 cc/min/l. 73f.l2 respectively. Urea and creatinine clearances were 8.5 and 8.6 cc/min/l. 731-: 2 . UF:<. was precisely regulated (avg 100 cc/hr) by attaching the ultrafiltrate tubing to a volumetric IV pump. This patient and 2 others died while receiving CAVIl, each in a setting of overwhelming sepsis and DIC. The duration of CAVH in those who died (17, 53, & 68 hrs) was similar to those who survived (27 &111 hrs). We conclude that CAVH using the diafilter-20 can be ef~ectively employed in critically ill infants and children enabling aggressive IV alimentation and co:::-'rection of fluid/electrolyte im1alance, but that specific indications for its use and potential impact on patient survival await further experience.

RESOLUTION OF IGM-II~DUCED RENAL FAILURE WITH PLASMAPHERESIS. Michael S. Linsey, Huntington Memorial Hospital, Pasadena, California. A 79 year old woman with oliguric acute renal failure (ARF) secondary to plugging of her glomerular capillary lumina with IgM and Kapoa was successfully treated with plasmapheresis. The patient presented with a 1 week history of vomiting, edema, and dyspnea. She had no purpura, Raynaud's, arthralgia, or leg ulcers. Oliguric ARF was noted on admission. BUN was 142 creat 6.9 (3 mos earlier creat was 1.3) C3 61 (nl. 85-180) C4 5 (nl. 15-45) Cryogl obul ins negative. HM negative. Serum IgM 83 (nl. 55-350) IgA 91 (nl. 70-310) IgG 677 (nl. 700-1600). Renal biopsy showed her glomerular capillary lumina were widely dilated and filled with proteinaceous precipitate that stained for IgM (4+), Clq (4+), C3 (3+), & kappa 1ight chain (4+). She was felt to have the renal lesion of macroglobulinemia or Type I cryoglobulinemia though clinically she had neither of these diseases. She remained in dialysis-dependent ARF until the twelfth hospital day when she underwent plasmapheresis. Her urine output then improved. and with repeat phereses her renal function returned to baseline. A subsequent bone marrow aspiration demonstrated only 5-10% mature-ap~earing lymphocytes and plasma cells but of these an abnormally high percentage had IgM, IgD. & kappa surface markers. Bone marrow biopsy showed no tumor. This patient thus appeared to have abnormal production of an IgM/kappa paraprotein which deposited within glomerular capillary lumina and caused ARF. Plasmapheresis, which rapidly removes IgM, led to resolution of her renal failure.

THO YEAR EXPERIENCE .IITH CITPvW;: AliTICOAGULATIOl':(CAC) IN ACUTE AKD CHRONIC HDiODIALYSIS (HD). Margaret HacDougall, Thomas l . ~iegrmnn, . Dennis Diederich, Univ. of Kai.1SaS, Kansas City, :(5, and KCV.t\l'!.C, :Zansas City, !:C. He hC'.ve collected data 0:1 950 ED procedures which were undertaken with C-AC Hithout heparin in 95 patients representing 6~' of all ED procedures over

a two-year period. C-AC Has used for 43% of all ();=1048) acute procedures. Clialyzer /membrane type

and patient access did not pose any li~itations. Double-luDen (DL) subclavian catheters '-Jere used in 59 and JL-femora~ in 14 patients. Scribner shunts 'vere used in 4 "?atients and a single lumen subclavian catheter in one. Gortex or fistula access was used in 35 patients for 460 procedures ~ ~'~umber of C-AC per patient varieC: between 1 and 73 without complications during long-term use~ The procedure ~las easy to perform "lithout additional staff superVISIon. Only 5 instances of equipment failure led to side effects during t~c early experience, including

2 episodes of dialyzer clotting due to inadequate C addition and 3 episodes of paresthesia due to insufficient calcium replacement.

Clinical conditions

of patients varied widely and ranged from patients ,V'ith acute perioperative bleeding after cardiac transplant to tbe routine use in ne,17 patients 'vith endstage renal disease. OUT experience supports our vietV' that

C-!.C represents the simplest and most reliable alternative to standard cO(}bulation~

AID

~1eparin

or other forms of anti-

CAPO, COST-EFFECTIVE TREATMENT IN OLDER, HIGH RISK PATIENTS. RC Mackow, WP Argy, PA Fields, JF Winchester,-rA-Ra-kowski, GE Schreiner, Georgetown Univ, DC To determine cost-effectiveness of CAPO in elderly (E, >55 yrs, n=32) vs younger (v, <55 yrs, n=79) patients (pts), we evaluated survival, technique survival,

hos~ital

RENAL PHOSPHATE HANDLING VERSUS PTH IN CHRONIC UREMIA Michael A. Madden, St. Louis University Medical Ctr., Department of Internal Medicine, St. Louis, Missouri

Percent Tubular Reabsorption of phosphate (TPR), N-Terminal PTH (PTH) and nephrogenous cAMP (NcAMP) were measured and maximal phosphate threshold \THPJ was calculatpd serially in 15 patients (pts) with

costs and incidence of non-renal

chronic renal failure (S creat ~ 3.0), using average of credtinine plus urea clearances to estimate GFR.

organic disease over 66 mos followup. Survival was worse at 24 mos in E, 67%, than V, 91% (p <0.05). Technique survival was similar, 77% and 84% at 2 yrs for E & Y, respectively. Average days on CAPO treatment were similar, 658 + 124 (mean + SEM) in E and 696 + 65 in V. In-hospital training cost was similar in the two groups $10,306 + 605 in E vs $10,469 + 769 in V (p NS). Non-training related hospital cost/pt yr is similar in E $29,244 + 7189 vs $19,699 + 4335 in V (p NS). Elderly pts have a higher incidence of non-renal organic disease on initiation of CAPO, 7/39 of E and 6/79 of V have >1 associated non-renal organic disease at initiation of CAPO (p <.05). Despite increased risk of morbidity and mortality associated with increased age and greater associated non-renal organic diseases in the >55 yr age group, elderly pts have a favorable cost-effective profile compared to younger pts over the 5 1/2 yr period of followup.

()

controls

19 Ca(mg! dl) 9.84±0.90 Pi(mg!dl) 3.43±0.65 TRP(%) 83.5±7.9 TMP(mgl dl) , 3.16±0.90

n

pts(all) 15 9.54±0.50 1 4.39±0.65 2

pts(PTH <30ps/ml) 5

9.73±0.47 4.0l±O.49 l 52.2±13.9 2 2.11±0.60 3

P, vs control ~ i <0.05; 2 <0.001; 3 "0.01 In patients there was no correlation between Ca

and PTH. PTH correlated linearly with Pi only when patients were subdivided into high and low PTH groups. PTH and NcAMP correlated logarithmically (r = 0.6948, P < 0.001). TRP and TMP showed inverse correlation logarithmically with both PTH and NcAMP (p <0.001). TRP and TMP were closelv correlated tn patients (r ~ 0.9602, P < 0.001), les~ so in controls (r = 0.5965, P<'O.Ol). TRP was the best pred1ctor of PTH>30 pg/ml. Using TRP <. 40% as positive, and> 50% as negati'Je, sensitivity = 94%, specificity = 78%, and positive predictive value = 94%. Only 22.2% or samples were inconclusive. falling between 40-50% TRP. TRP is a useful, inexpens1ve and readily a,ail able adjunct in accessing PTH activity in the patient with chronic renal failure.

FUNCTIONAL EFFECTS OF CHEMICAL IRRITATION OF THE PERITONEUM. J.F. Maher, P. Hirsze1, E. Chakrabarti. Dept. Med., Uniformed Services Univ. H1th. Sci., Bethesda, MD. Peritoneal clearance (C) of protein increases in response to peritoneal irritation. Protein exudation could represent an increase in capillary permeability or loss of membrane anionic charges or secretory release of protein from sources other than plasma (p). Sodium desoxycho1ate (des) irritates

MEMBRANOUS GLOMERULONEPHRITIS IN RENAL TRANSPLANTS Connie Manske, Keith Johnson, Gary Niblack, Alan Glick, Robert MacDonell, Robert Richie Nashville VA Medical Center and Vanderbilt Hosp, Nashville, TN. Membranous glomerulonephritis lMGN) developed in 16/706 renal allografts transplanted between 5/77 and 5/B4. The disease was de novo in 15. One patient developed MGN in 2 grafts. Six of the remaining 13 had had transplants in which MGN did not develop. No patient carried HBsAg. Twelve were white and 12 were male, similar to total transplant population. Eleven of 15 allografts were cadaveric. In white patients, HLA typing revealed a high incidence of Al(B/13), A3 (11/13) and DR2 (5/B). Average AB match was, 2.9 antigens. Immunosuppression included prednisone, rabbit ATS and azathiaprine (Az). Before developing MGN, 7/15 patients had decreased Az to 50 mg/day or less. Onset of proteinuria occurred within 15 months (Avg ; 9). Average proteinuria at biopsy was B.B mg/ mg Cr. Nephrotic syndrome (NS) developed in 6/15 patients within 5 months of proteinuria. Five of the six returned to dialysis within 11 months (Avg ; 7). Nine did not develop NS; 5 of these remain off dialysis after follow up of 19-44 months. Transplant biopsies showed stage 1 MGN in 11 allografts and stage 2 in 4. Repeat biopsy showed progression in 4/6. Regression was not seen. Four had associated transplant glomerulopathy, 4 had acute rejection, 4 had chronic rejection. All were negative for HBsAg and anti-rabbit IgG. Pathologic changes did not correlate with outcome. We conclude that MGN in transplants is not rare, especially in patients with certain HLA types or Az intolerance. NS carries a poor prognosis. Early biopsy may avoid unneeded rejection therapy.

the peritoneum increasing solute transfer rates,

decreasing dextrose gradient and ultrafiltration rates (UF). This probe was used to assess the functional response to inflammation. Control peritoneal dialyses of 6 rabbits were compared to dialyses with des (5 mg/Kg) added to dialysis fluid (D). UF was estimated by indicator dilution and C = (D/P) x (V/t). Neutral dextran was given IV 30 min. predia1ysis as a large (x 40,000 da1tons) uncharged marker solute. With des UF changed minimally from 0.27 to 0.24 m1/Kg/min and UF/gradient rose slightly from 8.1 to 10.4 ~l/Kg/min/mOsm. C urea rose from 0.58 to 0.91 m1/Kg/min (p
All

*

TIMING OF CYCLOSPORINE ADMINISTRATION IN PATIENTS WITH POSTTRANSPLANT ATN. A.Matas, V.Tellis, L.Perez, T.Quinn, G.Karwa, D.Glichlick, R.Soberman, F.Veith, Montefiore Medical Center, NY,NY. Cyclosporine (Cy) prolongs posttransplant ATN making the differentiation between ATN, rejection and Cy toxicity difficult. Outcome following cadaver transplantation in patients without ATN and started on Cy and prednisone (P) (Grp 1; n=37) was compared to outcome in patients with ATN (need for dialysis in the first postop. week) started on: a} Cy and P (Grp 2; n=18), or b} P and AZA or ALG and switched to Cy and P when serum creatinine fell 30% (Grp 3; n=26). One year patient survival was 97%. % Graft Survival Mean Creatinine 6 mo 12 mo 1 mo 3 mo 6 mo 12 mo 3 mo Grp 1 76 76 ~ 2.0 2.3 2.0 2T Grp 2 72 72 67 4.0 2.7 2.3 2.5 Grp 3 92 85 85 4.0 2.3 2.3 2.3 Graft survival was significantly better (logrank test) in Grp 3 vs 2 (p< .05); all grafts functioning at 6 months continue to function. Mean days on dialysis was 14.5 ~ 2 for Grp 2 vs 9.9± 2.2 for Grp 3 (p < .05). Mean serum creatinine in both ATN groups was higher at one month (p < .05) than in patients without ATN; at 3,6 and 12 months there was no difference. There was a higher incidence (N.S.) of viral infection in Grp 3. Mean hospital stay was equivalent and related to the development of rejection episodes in all 3 groups. We conclude that in patients with ATN better graft survival can be achieved by withholding cyclosporine until ATN is resolving.

DIAGNOSIS AND TREATMENT OF AL-INDUCED BONE DISEASE; EFFICACY OF DESFERRIOXAMINE(DFO). Marumo,F. ,Umetani,N. ,Kurokawa,K.l ,Ogura, Y .2,Ono, T.3,Suzuki,S.4 and Takahashi,y.5, Dept.Med.,Kitasato Univ. and l)Tokyo Univ. ,2)Jikei Med.Coll. , 3) Kyoto 1st Red-Cross,4)Shinrakuen,5)Sagamidai Hosp. ,Japan Al is known to induce encephalopathy and ostomalacia accompanied by bone pain in dialyzed patients.DFO was used in the DFO loading test to facilitate the diagnosis and treatment of bone disease in 117 maintenance dialysis patients. DFO loading test: For the test, blood samples were collected at the start of dialysis during the last hour of which, 40mg/kg or 2g DFO were administered. Samples were collected again at the start of the next dialysis. A correlation between serum increment by the DFO loading test(llAI) in 49 patients without bone pain(y) and the duration of dialysis(x) was found and could be expressed by the regression line, y=O. 88X+76. 9(n=49,r=0. 55). 63 out of 68 patients with bone pain placed above this line. By DFO loading, serum Al concentration increased to 328±.222(SD) %, with essentially no change in Fe( 112:::41%) or ferritin(l08!:29 %). The correlation of iPTH with llAI was slight(r=O. 2~. Therapy: 47 patients with bone pain were treated with 2g DFO/week. 26 patients became asymptomatic in 8.7= 1. 5(SE) weeks, 15 felt better in 7.4:.':1. 3 weeks, with 6 sensing no change. DFO treatment was effective for 87.2% of the patients with bone pain. II Al decreased 2, 4,8 and 12 weeks following the initial loading test(p < 0.01). AI3+- and Fe 3+-DFO stability constants were 10 20 and 10 27 , respectively, indicating serum Al to be strongly chelated while Fe weekly, despite its lower concentration than Fe. The present data show the DFO loading test to be clinically usefull for the diagnosis of AI-induced bone disease, and DFO treatment effective for eliminating bone pain.

DONOR-SPECIFIC SUPPRESSOR CELLS IN RENAL TRANSPLANTATION. M. Mathew, T. Kovithavongs, and J.B. Dossetor. Clinical and Transplant Immunology Group. University of Alberta Hospital, Edmonton, Alberta. Serial measurements of donor-specific immunological adaptive mechanisms in renal transplant recipients (R) were assayed using 2 donor-specific systems. In the 1st, the cell mediated lympholysis (CML) inducibility of pre and post Tx R cells to stimulation by donor (D) or controls (Y) was assayed (RDx, RYx, etc.). In the 2nd, the suppressive capacity of post Tx R lymphocytes on C~lL inducibil ity was assayed (RDx+R). Previous studies have shown that these assays may be useful as predictive indices of transplant outcome (Kidney Int. 27:345, 1985). Further experiments were carried out to detail the functional attributes & phenotype of suppressor cells (s.c.) detected in these assays. In the CML assay, kinetic experiments performed showed no evidence of accelerated kinetics. In the suppressor cell assay too no evidence of altered kinetics was detected and the putative s.c. were shown to be radiosensitive, particularly to over 1000 rads. Experiments to detect the optimum ratio of responder to suppressor, showed consistent suppression with both 1:1 and 1:0.5 ratios &variable suppression with 1:0.25 ratio. Using T cell subsets, prepared with monoclonal abo &complement, a greater degree of suppression was obtained with the T suppressor/ cytoxic subset suggesting that the putative suppressor cells belonged to this subpopulation.

~

THE ROLE OF ADULTERANTS IN HEROIN NEPHROPATHY Curtis Hoody, Robert Kaufman, Daniel McGuire, Susan Grossman, H. Yusuf Khan, Norman Lasker, Division of Nephrology, UliNDJ, Newark, NJ Heroin nephropathy characterized by focal glomerulosclerosis is a common cause of ESRD in black patients. Because of a lack of evidence for direct opiate nephrotoxicity it has been postulated that the renal damage could be caused by adulterants. In a preliminary 2-month study we examined the effect of daily IV injection of heroin with and without quinine, corn starch and lactose on glomerular morphology (pathologist "blinded"), proteinuria and serum creatinine jn male rats. Heroin alo~e produced the least glomerular damage while heroin + lactose produced the most. Based on these results the study was repeated to determine if lactose could produce the lesion in the absence of heroin (Table Ii Degree of Glomerulosclerosis*

0

l~

3+

Water Control Heroin + I
4 9 3 1

4 1 1 3

1

Table

4 4

* 0 = no mesangial proliferation 1+, 2+ = mesangial proliferation ()3 cells) 3+ = mesangial proliferation + sclerosis There were no Significant differences in the proteinuria or serum creatinine between groups. These results suggest that "glomerulosclerosis" can be produc~d in rats by chronic IV administration of heroin and adulterants. Lactose is capable of producing the lesion in the absence of heroin.

Al2

INFLUENCE OF ESRD DIAGIDSES AND POPULATION c::cMIDSITICN ON MJRTALITY IN NEIWORK 30. Alvin H. Moss and the ESRD Network 30 Staff, WVU School of Medicine, Morgantown, WV and Network 30, Richnnnd, VA. Patients with diabetic nephropathy are known as a group to have the highest mortality rate on dialysis. ESRD Network 30 conducted a mortality survey in 1984 to look at the contribution of diabetic nephropathy and other ESRD diagnoses to dialysis unit mortality rates in excess of the Network mean. Virginia (VA) dialysis units were compared to those in West Virginia (WV) using data from the Medical Information System. From 1982-84, the mortality of VA patients was 15.8 ± 2.2% compared to 19.8 ± 2.6% for WV (p < .10). The prevalence of DN in VA during this time was 14.8 ± 3% compared to 19.3 ± 2.1% in WV (p<.05). The incidence of DN in VA was 24.5 ± 1. 7% canpared to 27.5 ± 6.1% in WV (p~NS). The mortality rate for VA diabetics was 24.2 ± 3.9% not different from 24.0 ± 6.1% for WV diabetics. The mortality rate for VA non-diabetics was 14.2 ± 1.9% which was lower than the rate of 18.3 ± 2.3% in WV (p<.05). Nephrosclerosis was the leading cause of ESRD in VA causing 33 ± 0.6% of all new cases canpared to 25 ± 2% in WV (p < .0025). Blacks canprised 58.2% of all VA dialysis patients compared to 14.4% in WV. In conclusion, the higher mortality rate for WV dialysis patients is partly explained by a greater percentage of diabetics who experience a higher mortality rate than nondiabetics. Other factors including differences in racial compOSition and causes of ESRD appear to contribute as well.

()

SOCL~L SUPPORT OF SPOUSES OF PATIENTS ON HEr~ODIALYSIS. Christine L. Mudge. Veteran's Administration Hospital, Martinez, California. This descriptive study examined the relationship of social support to well-being in spouses of patients on chronic in-center hemodialysis. Twenty-three spouses, aged 35 to 82 years and married at least 1 year to patients from one of three different dialysis units, were administered a demographic questionnaire, the Norbeck Social Support Ouestionnaire, the !'1ental Health Index component of the Rand General Hell-Being Questionnaire, and an unstructured open-ended interview. It was hypothesized that, as social support increased, so would well-being. Results indicated that social support and well-being did positively and significantly correlate. The longer the patient was on dialysis, the greater the spouses' perceived -social support and sense of well-being. The wives of patients on dialysis had higher levels of anxiety and psychological distress and lower levels of well-being than did the husbands. The qualitative data indicated that spouses reacted to patients on dialysis with feelings of depression, guilt, and anger; and perceived their situation to be one of increased responsibility and isolation due to changes in patient behavior. Family and relatives were identified by 22 spouses as a source of social support, and personal religious belief by 19. A social support peer group or resource person could provide a means of social support and increased well-being.

DISCREPANCY BETWEEN HISTOLOGY AND FUNCTION IN THE HIGH PROTEIN FED REMNANT KIDNEY MOnEL. N. Narasimhan,* DC Houghton, TA Golper, WM ~nnett. Oregon Health Sciences University. Portland, OR. Several investigators have demonstrated accelerated progression of glomerular sclerosis (GS), tubulointerstitial fibrosis (TI), and cystic dilatations in the remnant kidney-high protein intake model. We studied 3 dietary regimens (pair fed) and their effects on renal architecture in 5/6 nephrectomized S-D rats. Group 1 (Gl) were fed a 14% protein diet for 6 mos., G2 fed ~7% protein for 6 mos. and G3 fed 37% protein for the first 3 mos. then 14% protein for 3 mos. There were no differences in S or Cln in Gl and G? at 3 or 6 mos. but histologicaTly these groups were quite different. The severity of each of the changes were scored on a scale of 0 to 4. G Mos. (/-l) GS TI Cysts Total T 3 (8) 0-:88 1.0 ~ T.;6 (13) 1.4 1.8 1.5 4.7 2 3 (8) 1.5 1.5 1.0 4.0 6 (13) 3.0 2.6 2.6 8.2 3 6 (7) 1.9 1.7 1.6 5.2 Conclusion: Despite similar Scr and Cln with all diets, high protein intake leads to more pronounced histologic changes that includes glomerular sclerosis, interstitial fibrosis, chronic inflammation and cystic changes. These cystic changes could be similar to the early stages of acquired renal cystic disease in uremic humans.

LONG TERM OUTCOME OF CAPD: THE SOUTHERN CALIFORNIA/ SOUTHERN NEVADA EXPERIENCE. A.R. Nissenson, D.E. Gentile, R.E. SOOerblan, C. Brax, Medica 1 Review Board, NCC #4, Los Angeles, Ca. The NCC #4 CAPD study inc ludes data on all patients (pts) started on CAPD in Southern Ca lifornia/ Southern Nevada fran early 1979. It is designed to assess the long term efficacy and morbidity of this mOOa lity. As of 12/31/84 data on 1061 pts. with over 1387 pt-yrs experience has been analyzed with the average pt on CAPO for 16 mo. 26 patients have been followed for five years. Compared to NCC #4 HD pts, those less than 20 y.o., men, whites, and those with CGN as a cause of ESRD are overrepresented on CAPO. Life-table analyses reveal: Pt. surviva 1

*death uplt

&

.L.1L

~ ~

88 78 76 59 48 37 38 27 transplantation considered

% staying on CAPD* % free of peritonitis % not hospitalized

.!E

~

67 43 60 48 38 24 32 32 32 22 24 22 "lost-to-follow-

Pts. spent 16.2 days per yr. in hospital, 5.3 of those for peritonitis and 4.8 for other CAPO-related problems. Of those dropping out of CAPD, 52% did so because of peritonitis, exit site or tunnel infection, 15% because of pt or family choice and only 10% because of inadequate dialysis. In summary, CAPD is proving a viable long-term form of ESRD treatment. The initial high drop-out rates reported seem to have dec lined substantia lly, though infection remains the leading cause of technique failure as well as morbidity.

Al3

()

FENOLDOPAM: AN ORAL DOPAMINERGIC DRUG FOR THE TREATMENT OF HYPERTENS ION. .H.e~n.i.Q N.Qg.u~.i-,_g" Te r ry Me r ke 1, and Ral ph E. Cutler-Lorna Linda Veterans Hospital, Nephrology Section, Lorna Linda, CA. Fenoldopam, a benzazepine derivative that selectively dilates renal and mesenteric arteries, acts on the postsynaptic dopaminergic receptors and may have clinical application in hypertension. 15 subjects were studied after a 21 day placebo period when the mean diastolic blood pressure (DBP) was 100 ± 5. The ini tial starting dose was 50 mg BID. The dose was increased by 50 mg every 8 to 10 days to a total of 200 mg BID i f the DBP did not decrease by 10 mmHg. After the initial dose and each initial increase, BP was evaluated every 0.5 hour for 3 hours and similarly at days 3, 8 and 10 after the increase. After the first dose in all periods, there was a significant response in the mean systolic and DBP at 0.5 and 1 hour only. Predose mean DBP at day 8 during period 1 was 93 ± 9, P >0.05. I f a DBP decrease greater than 5 mmHg is considered significant, only 8 of 15 responded. Only 4 of 15 had a decrease greater than 10 mmHg in DBP in period 1. Increasing the dose in periods 2, 3 and 4 did not increase the number of responders. For clinical use, fenoldopam will need to be given intravenously or in a sustained release form.

()

DOES RACE AFFECT RENAL TRANSPLANT RESULTS - A SINGLE INSTITUTION STUDY. D.Odenheimer, A.Matas, V.Tellis, T.Quinn, D.Glicklich, R.Soberman, F.Veith. Montefiore Medical Center, New York, New York Multicenter studies have shown decreased graft survival following renal transplantation to black recipients. We studied the effect of race on transplant results at a single institution where immunosuppression for each time period was consistent, and there was a wide range of socioeconomic conditions for each racial group. Between 1/76 and 4/85, 358 patients underwent cadaver transplantation. HLA and Dr matching was not used; pretransplant transfusion was started in 1979; cyclosporine was first used in 1983. There was no difference in patient survival (97% @ 1 yr). Similarly there was no difference in graft survival for the whole group, or for patients transplanted with cyclosporine) (Table). % Graft Survival 1976 - 85 Cy only (1983-85) Recipient s• Race ~ ~ Black (n=120)~ (n=27)~ Caucasian (n=166) 51 40 (n=39) 72 72 Hispanic (n=62) 57 37 (n=19) 69 62 Strikingly, although 51% of our patient population is black or hispanic, only 12% of transplanted kidneys were from black donors and 7% from hispanic donors. Kidneys from caucasian donors resultpd in equivalent graft survival when transplanted to caucasians, blacks or hispanic recipients (63%, 62%, and 68% at one year respectively). We conclude that when socioeconomic ard immunosuppressive factors are similar, race is irrelevant to renal transplant results.

~

\r

DETRIMENTAL EFFECT OF CYCLOSPORn:E (CY) ON INITIAL FUNCTION OF CADAVER RENAL ALLOGP~"FTS FOLLOHDIG EXTENDED PRESERVATIOli: RESULTS OF A RANDO~UZED PROSPECTIVE STUDY. Andrew C. Novick, Rwei Ho Hsieh, Donald Steinmul1er, Stevan:5treem, Robert Cunninghaw, Diane Steinhilber, William Braun, j'iarlene Goormastic,

Caroline Buszta, Cleveland Clinic Foundation, Cleveland, Ohio. From December 1983 to SenteI'i.ber 1984, 56 cadaver transplant patients were entered into a randoreized prospective trial comparing naintenance immunosuppression with cyclosporinc and prednisone (CY group, N=25) to a regimen of azathio~rine, prednisone, anc. prophylactic antilyc:phocyte glo;'ulin (ALG group, 1-:=31). These two groups were \vell r.:atched for maj or determinants of graft outco~e and the mean renal preservation tine '\vas 37 hours in each group. The incidence of post-transplant acute tubular necrosis vJaS 58% in the ALG group and 72% in the CY group (P=.28). There were 5 cases of primary non-function (PNF) in the CY group and only 1 in the ALG group (P=.05). Of those grafts which functioned, the nean serun creatinine nadir (1.5 vs 2.2 ~lg/dl, P=.06) and the nean nmlbcr of days to reach this nadir (24.2 vs 43.3. days, P=.OJ) were both less in the ALG group. Nore !Jatients in the ALG group experienced rejection episodes (65% vs 24%, P < .005). Actuarial one-year graft survival in the ALG and CY groups is 78% and 48%, respectively (P ~.05). This difference :':"s mainly due to the large nunber of PNF grafts in the CY group "Jhich ue attribute to the effect of Cy's nephrotoxicity sUf.lerinposecl on renal ischemia incurred prior to transplantation. In order to realize the full benefit of CY in cadaver transplantation, renewed enpilasis Dust be placeci on minimizing ischemic renal dacnge.

2,lr

A14

ASEPTIC NECROSIS IN RENAL TRANSPLANT RECIPIENTS. PS Parfrey, D. Farge, NA Parfrey, JA Hanley, and RD Guttmann. Royal Victoria Hospital, Montreal and Health Sciences Centre, St. John's. To elucidate the causes of aseptic necrosis (AN) we studied all 26 transplant patients with AN and 42 controls matched for year of transplantation, age, and sex. Patients transplanted before 1971(when incidence of AN was 29%) received significantly more intravenous solucortef and less intravenous solumedrol, had higher BUN levels at time of starting dialysis, had lower serum calcium and higher serum alkaline phosphatase at transplantation compared to patients transplanted in or after 1971 (when incidence was 4%). Development of AN was not related to duration of dialysis before transplant, severity of uremia at time of starting dialysis, adequacy of dialysis before transplantation, transplant dysfunction at time AN was diagnosed, hyperparathyroidism before or after transplantation, fatty infiltration of liver, total steroid dose 1 or 4 months after transplantation, total number of intravenous doses of solumedrol or solucortef. However, BUN during dialysis period was Significantly higher in aseptic necrosis group. 27% of AN group had a previous transplant compared to 5% of controls. Half the AN group (5/10) had parenchymal iron on liver biopsy 1 year after transplant compared to 15% (2/13) of those without AN. The incidence of AN following transplantation has decreased significantly during the past 13 years. Possible risk factors for aseptic necrosis may include previous transplantation, severe iron overload, and increased protein catabolism/turnover during dialysis.

THE OUTCOME AND COMPLICATIONS OF THE DiaTAP bioCarbon (R) BUTTON-GRAFT VASCULAR ACCESS DEVICE IN HAEMODIALYSIS PATIENTS. M.D. Paul, P.S. Parfrey, D. Marshall, V. Aldrete, L. Purchase and M.H. Gault. Memorial University of Newfoundland. The DiaTAP bioCarbon vascular access device is an inert, biocompatible, vitreous port placed transcutaneously which permits hemodialysis without needles. The outcome and complications which developed in eight hemodialysis patients who received twelve DiaTAP bioCarbon button vascular access devices were reviewed. All patients had a poor vascular access history (number of fai led accessess ranged from 1-8, mean 4). Patients were followed for 1-22 months (mean 13). Three of twelve devices were replaced because of thrombosis and two because of infection. The average functioning life of the DiaTAP was 9.4 months (range 2 days - 20 months). Two further devices have become infected necessitating long-term antibiotic therapy but not removal. One patient who had a left jugular-external carotid device died from a septic episode, possibly arising from the DiaTAP button. Four patients have had ten episodes when blood flow was reduced or lost. Streptokinase infusion into the DiaTAP button usually at low doses, led to improved blood flow in 8 of 10 episodes (from 85 ± 56 to 177 ± 40 cc/min. Improved flow occurred after insertion of a curette into the button in one streptokinase failure, and replacement was necessary in the other. Despite these problems, the DiaTAP vascular access was found to be a valuable means of establishing effective access when more conventional forms of access were impractical or had failed. Using our data plus previous reports, the 6 months survival rate of the DiaTAP access device was 77%.

3mtA~~(~):G~.SPECIRAJamp~~~~

J:;;rNeuroretrics ~l1t.of Ped., T~le U loc, New York, NY.

ROLE OF EXIT SITE INFECTIONS IN LOSS OF PERITONEAL CATHETERS. B. Piraino, J. Bernardini, M. Sorkin. Renal-Electrolyte Div., University of Pittsburgh, Dept. of Medicine, Pittsburgh, PA. Peritonitis (P) is often considered to be the most common cause of peritoneal catheter loss. To investigate other causes we collected data over a 5 year period on 137 patients (pts) on CAPO 3 to 46 mos. There were 178 catheters utilized during the study period. Out of 52 catheters removed from 39 pts., 5 (10%) were lost due to mechanical failure and 47(90%) were lost due to a peritoneal dialysis related infection: 13(25%) for P, 10(19%) for recurrent exit site infections (ESI), 4(8%) for tunnel infections (TI), and 20(38%) for simultaneous ESI, TI and/or P. Pts were grouped based on whether there was a history of ESI and/or P to determine the association of ESI, P and catheters lost. The % of pts in each group who lost catheters is as shown: pts with ESI pts without ESI pts with P pts without P

()

To evaluate the neurologic status of children and adoleoc.ents with am rest;ing m; FS -.ere quantitated bv canputer with neuroretricsCiM): data -.ere collected for each of 4 fr~uency 00nds and 8 scalp e1ectrcxle positioos, quantitated by Fast Fourier Transform, and ~referenced to previously-derived 00= bv z-transfo)1IJiltion. 1\.0 I-tailed nrultivariate statistics the I1lturational f.ag(l:1L) and Fuoctional Deviation(FD) -.ere deri~ fran each ~tient(ptJ's set of 32 univariate z~res~such that an abnormal I'lL indicated a develop!8ltally delayed FS ror age, am FD, the presence of underlying organic aysfl.D1Ction. Values >l.~.OS vs age-re1ated 00= and -.ere COIISl.dered abnormal. Eigl}ty::eigl]t 1M exans .ere performed in 70 pts: 22 with chronic renal failljI"e(rnF) (GfR"26±32.5lx:.!s.d. ]); 19 with ESRD studied pre-(Pre-fl') and/or JlOI'!I:-(Post-U') dialysis; and 31 in t.r;'!nllplantl1ts(Txl(GfR;.m.St36). I-mri ML \03S s:i,grriricantly lo.er in Tx(.36±.56) vs OW(l.38±l.78,O<.OO5), Pre-IF(I.44!:1.3l, 0<.(01), and Post-U'(l.l9±'~l~.ool). Chly 2/31 Tx(6.5%) had a ML ?>-~l, vs 8/22 rnF(36~i X -;>,69,p<.02). I'mn ML in CllF with GfR '10 2.94±2.1S) was sigl1.llicanli~>lfl tOOse with GfR>10(.65±.89,p< .(03) am Tx at all levels ~f GfR ~ 12.2-120)( .36±.56, P< .0000(2), suggesting that a . . icantly delayed 1E:; FS ror age does oot appear untll near levels or GfR are reactJed. The nmn difference in ML for 10 pts studied pre-(2.Ol±l.47)vs pos!\03S

also significant(o<.OO4,Jmred t-test).

7/29 (24%) 0/36 (0%)

The % of pts who lost catheters in the groups with ESI vs those without ESI was significantly higher, independent of the effect of P (Mantel Haenszel test, Z=3.8, p<0.003). The % of pts who lost catheters increased with time on CAPO (16% of pts on 3-12 rna, 30% on >12-24 mo., 55% on >24 mo, lost lor more catheters, x2 = 14.9, p
Gruskin, Broce Kaiser am I-W.Sch., Phi1adeljhla, PA,

(.2A±.33) Tx

30/46 (65%) 2/26 (8%)

HTLV-III STUDIES IN ESRD PATIENTS. C. Lynn Poole, Dana O. Johnston, C. Freer, A. Morrison and F. Westervelt. Dept. of Medicine, Univ. of Virginia, Charlottesville. Multiple blood transfusions are a risk factor for HTLV-III antibody positivity. We tested 79 regular dialysis patients; 23% were age 20-39 years at time of survey; 48% had been on dialysis 3 or more years. We are surveying our transplant recipients.

Four (5%) were initially antibody positive (ELISA, Abbott Lab method). Three were confirmed positive by Abbott Labs; 2 were Western blot negative, 1 was equivocal. All 3 ELISA positive patients had received multiple transfusions, 2 of these in the context of cadaveric transplants rejected after 2 and 6 years.

None had hepatitis B antigen or antibody, although 2

had received vaccine. Helper:suppressor was low in 2.

Assessing the HTLV-III antibody status of dialysis

patients should enhance protection of health care wor-

kers by minimizing exposure to infectious body fluids, and can further understanding the bioepidemiology of

r-mn FD

this infection. While current testing methods do not assure precise identification of infectious patients, we carry out dialysis machine cohorting and isolation

\03S lo.er in Tx(l.6tl.Q) vs Post::!JP(2.38±1.57,p<.OS), but oot vs Pre-IF or rnF, and 15731 Tx( 48.l,%)still had an abnonnal FD. I'mn FD was hi~ an;ng aw with GfR 1O(1.45±l.OSl~.0l5) am ~ Tx with GfRaJ 2.l4±1.06) vs those with GfR>9O(l.ll±.77,P<.03).~ting that tends to be IOOre abnormal in pts with lo.er Gffi's:~lhe nmn difference in FD for 10pts studied pre-(3.01±1.82) vs poI'lt-(l.53±.97) Tx Io3S also silmificant (0<.025 paired t-test), but-S/lO"Tx (:iff,) still had a FD>I.64. Ihm FD, but oot ML, \03S also higher with vs without a seizure history.in rnF(3.63:i:3.07 vs 1.45H.l,~.cm.»)...,Pre-IlP(3.7±2.37 vs l.59±.94 I P<.OSJ, and Tx (2.21±1.07 vs 1.34±./j1j,0<.(26). Thus, a seizure matheslS \03S reflected by an abnormal FD, but not ML. m; FS IIBy be quantitated in dri.ldren with am by 1M; clinically re1event patterns of abnormality IIBy be identified and differentiated py ML and FD. linProverent in ML Io3S seen with trnnsplantation(T), bUt evidence of organic dysfuoction(FD>l.64) persisted post-T in lIBIly pts. The ML aild FD IIBY prove useful in assessing the reversibility of CNS dysfl.D1Ction occurring with ESRD in dri.ldren. "Calculated creatinine clearance, ml/nrln/l. 73ri2

of HTLV-III positive patients so as to minimize trans-

mission to uninfected persons.

Pt. Age Dialysis Trans- Trans- ELISA Western T4:T8 Sex mos. plant fusion blot 11M

RG EC

A15

44 F

CAPD 20

CAD 2/83

n=12

+

0.54

26

Hema.

CAD 8/78

n=29

+

0.83

57 F

Hema. 30

n=18

+

M

12

+/-

UNRESTRAINED RABBIT MODEL FOR PERITONEAL DIALYSIS (PD) USING AN IMPROVED CATHETER DESIGN; RESPIRATORY FREQUENCY (F) INFLUENCES DIALYSATE ABSORPTION. *Andreas H. Pust, Lee W. Henderson. VA Med. Ctr. San Diego, CA. Quantitative and rapid dialysate (D) volume (V) drainage without residual volume is critical in small animals, thus other models require prior omentectomy or general anesthesia and unphysiologic posture or open peritoneal cavity. Fourteen unrestrained and fully awake rabbits underwent PD with a new multi holed silicone catheter (7 * 400 mm), that provided fast drainage of 40 ml/kg in 5 min without residual volume. During an isotonic (ISO) exchange (E, all 120 min) the absorbed V showed a high correlation to the average F (r=0.84, p=O.Ol, n=9, y=0.006 * x-0.22, ml/kg/min). F (l/min) was 56±2 during the first ISO-E, 58 during another, but increased Significantly (p=O.OOl) during both subsequent hypertonic (H) F(H)=77±3 and hypotonic (0) F(0)=80±5 (n.s., n=60). After 2 exchanges all animals had bilateral pleural effusions (P); P(H)=31±4, P(0)=9±3 (p=O.OOl, n=ll, ml), V was then V(H)=63±2, V(0)=12±3 (p=O.OOl, n=14, ml/kg). Intraperitoneal pressure changes or lymphatic valve mechanisms by diaphragmatic movements can increase uptake of dialysate, but the amount of pleural effusions depends on the osmolarity of D and the V. The amount of P by itself cannot explain the increase of F. Rabbits have leaky diaphragms and careful appreciation of F is necessary to understand fluid transport in this model.

ACUTE RENAL FAILURE (ARF): AN ANALYSIS OF 56 SURVIVORS. KathLyn L. Popowniak and Emil P. Paganini. Cleveland Clinic Found., Dept. of HypeLtension and NephLology, Cleveland, Ohio. Fifty-six sULgical patients (38 men; 18 women) who LequiLed hemodialysis fOL and LecoveLed fLom ARF weLe analyzed to deteLmine if sexual diffeLences played a Lole in Lecovecy. The mean age (YLS.) of the men and women was 60.8 and 56.4, Lespectively. The main pLimaLY disease of both sexes involved the gastLointestinal (g.i.) tLact. VasculaL and genitouLinaLY (g.u.) tLact disease weLe the 2nd and 3Ld mcst commcn pLimacy diseases fOL men. Diseases of the heaLt and musculoskeletal system Lanked 2nd and g.u. tLact and vasculaL disese Lanked 3Ld in women. Ischemia was the main etiologic factoL (76.3% men; 72.2% women) followed by nepLhotoxicity (7.9% men; 22.2% women). Combinations of ischemia, nephrotoxicity, and sepsis ranked 3Ld in both sexes. Women required an average of 4.1 and men 6.7 dialyses. The mean recoveLY time (days) - time between onset of ARF and diuresis - was 22.4 for men and 17.8 for women. The aveLage time of hospitalization was 50.7 and 50.2 days for men and women, respectively. The major complications fOL both sexes was infection. Complications involving the g.i. and centLal and peLipheral nervous systems ranked 2nd and 3rd, respectively for both sexes. This analysis reveals that in the 33.5% of recovered ARF patients, there were marked similarities in the primacy diseases, numbeL of dialytic treatments, hospitalization time, etiOlogic factoLs, and complications involving both sexes.

OF SI9S ~:y SIDz::' !lJi\~~ LTn~E~ .sTJ~CLAVI.~~·! (DT..... C) =-o~ :~B~~O!)I~L'!S=S. ~e~ib ~~. ~aja,

F:VALUATIO~

C.~TES~ERS

~:~~a~~* K:~~e~;t~~~?~~~L~;n~~;(:'S~~~:;t ~~~~~e~;



fo1ed. Ct~., K-.:-a:FtsolJ Div. of Neryh., F~"ll]E!.., sp.. Sic.e lJy Ride DLe 3~e i 1")c=~asi!1g1y ~ei!')g w7ed as ~em!)o"""ary

access fo!"

~e:nc~iaJysis

("o:n!·)a.=e~ au?" eXDe~i.en~e loJj

(RD).

'!'l-:is st'..l8.y

t'1 Sl-..ilE"Y (Sl-}) DLe

genesis of thromboembolic disease in cadaver transplant recipients. We analyzed our experience

f~nd

~~~~~~" ~;~; ]~~c a:~n;~~q~:c;~::~e e~~~' :::~'1 c:;~:~~:~:

with thromboembolism in 240 consecutive patients (pts) who received cadaver renal allografts between May I, 1980 and April 30, 1985. Our immunosuppression protocol consisted of Azathioprine, Steroids and ALG. None of the pts received Cyclosporin A. During a mean follow-up of 21.3±17.4 months, 21 patients (9%) developed 25 thromboembolic complications. Pulmonary embolism 7, deep vein thrombosis 9, thrombophlebitis 4, hemorrhoidal thrombosis 3, renal artery thrombosis 1 and femoral artery thrombosis 1. Ten of them were males and 11 were females. Their mean age was 45.2 years (range 19-68) and mean interval between transplantation and thromboembolic event was 12 months (range 0.2 55.4). Three pts died of massive pulmonary embolism at 0.2, 2.7 and 3.5 months post transplant respectively. Surgical embolectomy was successful in the patient with femoral artery thrombosis, but not in the one with renal artery thrombosis. The complications in other pts were managed successfully with medical treatment. Our data suggest that 1) thromboembolic disease is a significant problem even in pts

tion and handlino. .n..t t~e r:>'lC of f-lD, ':"at'1ete-r-s wpre fille~ \V'i t~ "leDa; in ane no inte;.cialytic i!1fusions we~e us~d _

'I'!1e cat!1et~':':"s w~!""e

!"eMOVec. on~

y ·.-vh~n. no

longer needed O-r::" ::~e'::"~ was clotting, mA1fuYlC'tio:1 ?:1-:'l/ or in£~ctio:1. ~·i +tv six SLC '''Are insA::::ec =-n 48 ~ts fo.!" 271 tID, 53 E=r:t nT.... c iT) 45 ')ts for- 16t. HD ann 75 QU DLC in 62 nts :'0:: 301 !..fD. E.!)/ca~~e:'er 'yp"""e 4·.9, 3.). anc 4.0 while % su')e:;:,:""ici2.~ i nf"ect.ion \0128 6 I ~. nne ~ fo: SLC I Sh Df. and Qu 9L !""es:")f,~('ti VA] " . 'T'here ~v2.s no septicemia. ~D/r('!t~v":'!ter :::OM ~~.t. c:;j.cP ,.,e>;r12 4.5-, 2.0 and 3.0 and from ~t sid~ ~e~e 5.3, 3.4 an~ 4.3 ~it~ S~.. C, C::hDL 2nd Qu9[. re:qp2rtivply. rn,vo T)h~ had f'u!")prior vpna cava ru>"")tu:o--e ~ 1 'i'.': t.h S,.!)T..... ano 1 '-.1i t~ QuDL) and 1 aortiC' b]J~<::,di!1q !1eeci:1g tho~acj.c SU::g9:Y. .-<';1. 1 com'Jlic2.tio:1s occ:u:;r;(l 1vith ~,t i':1sp~tions. Poo:- :10'-'1 W?.B· rno:!':""? +.;-eO'.lAn':. on T_.t si~e 'vit~ .shD~j (8/12) n:J..4 QuDL (9/2~.) ~ut no:: \vi t~ SLC (3/23). 'T!1ese da~a suq~est t~at rlai01- cOITIT»)_icat.io~s ;:,nG f1eC~a:;1iC2l n:o~J A'11~ ~ay ')e more ~regue:1':. in DLC i:1sp::--tec. 0:1. Lt eire t~a'1 0:1 ~t eic~. !ns o ;-tio!1 0: DLC on :,t f'i-:'le ~~Oll2.rl l:~ n::efprrec.. As 1'T]"':--l-:ir.:1ical ")ro1;:)].P'llS 'tle:-:-e :10t ~""""O'qu"?:1t 0:1 Lt SiCA wi t'1 ~~.r:: l i t May ~(>- desi::a~:J.p to UEe '3LC in pr'2~e!'enc~ t.o 9L,C on !...t side ·.oJ~A!1 ~t side is JO~

receiving conventional immunosuppressive drugs,

2)

other factors besides cyclosporin A should be considered in the pathogenesis of thromboembolic disease in renal transplant recipients.

'oJi t~ t~e u~p of aSADt.i.c D.!"oci"1u~ions, c;:pntj cemia ca:1 ':e r)!"E'ventec in SUl-r:::'.2.'ri2!l .,f;CE'RS_ rprailab2 e _

~ur::'H')r

THE INCIDENCE OF THROMBOEMBOLIC DISEASE IN RECIPIENTS OF CADAVER KIDNEY TRANSPLANTS. K.V. Rao and R.C. Andersen. Univ of Minnesota and Hennepin County Medical Center, Minneapols, MN. A recent study from Belgium (Lancet 1:999, 1985) has implicated cyclosporin A in the patho-

i!11l};o'rp;Tlen':. in .9LC c.esig:1 is '1Al?dec.

A16

WHEN AND HOW TO TREAT URINARY TRACT INFECTION: "THE UROLOGIST'S VIEWPOINT." James A. Roberts, Tulane University School of Medicine, Dept. of Urology, New Orleans, Louisiana.

~

To begin, we must define urinary tract infections, as some are only asymptomatic bacteriuria, which require no treatment as they only represent colonization of the urinary tract as opposed to invasion. The conditions under which colonization occurs require understanding of both the host and the parasite involved. Thus colonization is due to bacterial adhesion usually by means of bacterial fimbriae. Certain fimbriae seem capable of only bladder colonization with ensuing cystitis. Others colonize and cause no disease while as yet others appear to be nephropathogenic and produce both colonization and invasion of the kidney, i.e. acute pyelonephritis. Thus, knowledge of the bacterial parasite causing the disease assists in the decision as to the means of therapy. The indications for therapeutic regimens ranging from single dose, one day, three day, and the day treatment for acute infections can thus be explained. Prophylactic therapy ranges from single dose at the onset of symptoms to daily or post intercourse medication. The relative indications for these therapies can also be understood if the host's history and causative bacteria are considered.

DIALYSANCE AND RADIATION HAZARD OF 1131 IODOHIPPURAN STUDY IN A HEMODIALYSIS PATIENT. Steven J. Rosansky, and Nick Detorie. WJBD Veterans' HOSP1ta I and the Uni v. of South Carol ina, and Dept. of Radiology, Columbia, South Carolina The radi ation hazards to patients and di alysi s staff related to dialysis treatments after a radioisotope procedure has not been well studied. We exami ned the effects of admi ni steri ng 300 mi crocuries (uCi) of 1-131 iodohippuran (I) for a renogram study to a patient who received 3 hours of hemodi alysi s illllledi ate ly after a I study. Radi oactivity in blood (measured half hourly) and urine samples adjusted for sample volume and physical decay were measured by the use of a sodium iodide we 11 counter. The total number of uCi removed by dialysis was estimated by the product of the dialysance (ml/min) of I multiplied by the average concentration of I in that given time period. 2 During 3 hours of hemodialysis utilizing a I.Om parallel plate dialyzer and a Century 2 single pass hemodialysis machine, the: average whole blood radioactivity from I was .0015 uCi/ml; average dialysance for I was 60 + 12 ml/min; 31 uCi of I were removed by dialysis;-6.0 uCi of I were excreted in the urine. Negligible radioactivity was detected post dialysis in the dialysate compartment of the hemodi a lysi s machi ne. After cl eaning the machine with 10% formalin all residual I counts were removed. In conclusion, dialysis after administration of 300 uCi of I to a dialysis patient with minimal renal function: does not result in any significant contamination of a single pass hemodialysis machine; results in low blood radioactivity with little danger to dialysis staff.

o

A17

THE EFFECTS OF BETA-BLOCKERS ON THE SERUM POTASSIUM IN CHRONIC HEMODIALYSIS. Michael Robson and Victor Pollak. Dept. of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio. It has previously been shown that beta-blockers may increase the predialysis potassium of patients on chronic hemodialysis. We therefore examined 50 patients who were undergoing chronic hemodialysis for end-stage renal failure and who were receiving beta-blockers. The patients had been on dialysis for a mean time of 37.8 months and had taken betablockers for an average of 10.6 months. Atenolol and propranolol were most frequently used for the control of hypertension. The average dose of atenolol was 62 mg and propranolol was lOB mg/day. Each patient was evaluated before and after taking beta-blockers thus each patient served as own control. Of the 50 patients 21 showed a rise in potassium, 19 a fall and 10 no change. The average serum potassium was 4.8 ± .62 before beta-blockers (n=1944) and 4.9 ± .69 after (n=910). These results did not differ significantly from the serum potassium of all our 370 patients which was 4.B ± 1.0 (n=25B04). There was no change in the intake of potassium, protein, or calories, or in blood flows, duration of dialysis, dilysate flows or transmembrane pressure during the two periods of study. Bicarbonate, BUN and creatinine levels were also unchanged. Nine patients also received non-steroidal antiinflammatory drugs; there was no consistent effect on serum potassium. We conclude that in hemodialysis patients betablockers do not influence the predialysis potassium levels significnatly.

RESULTS OF CORONARY ARTERY SURGERY (CAS) IN PATIENTS WITH ESRD. S.G. Rostand, K.A. Kirk, E.A. Rutsky, NRTC, Univ. of Alabama at Birmingham, Birmingham,AL. CAS is now done more often in ESRD patients to reduce morbidity and mortality of symptomatic coronary disease which remains a leading cause of death in these patients. To examine the results of CAS in ESRD we studied the records of 39 ESRD patients with angiographically (CAG) proven coronary disease. Twentyfour underwent CAS. Their clinical course was compared to that of 15 controls who were not operated. The groups did not differ in age, race, sex, or duration of renal replacement therapy (RRT) to CAG. The CAS group had more 3-vessel disease,glomerulonephritiS, and diabetes while the controls had more hypertension. CAS relieved angina completely in 14 and gave partial relief to 6. Life table analysis showed no difference in 5 year survival between groups starting from either onset of RRT (77 vs.73%) or from CAG (57 vs. 55%). Five of 10 deaths after CAS were in older patients, within 12 months of CAG; 4 deaths were intra-or perioperative. Only 1 of 7 deaths in the non-CAS was in in the first year. All deaths were vascular disease related; 2 from MI in the CAS group. Cox regression analysis to assess the relative contribution of various factors to mortality showed that older age, female sex, hypertension and shorter interval from onset of RRT to GAG were associated with death in CAS patients but not in controls. The data show (a) CAS is effective in relieving angina in ESRD; (b) CAS had a 21% first year mortality; (c) older patients, women and hypertensives had an increased mortality. We conclude that since CAS has no effect on survival and had a high mortality, it should only be considered for relief of angina.

FREQUENCY OF METHICILLIN RESISTANT PERITONITIS. J. Rubin, C. Adair,* and G. Case.* Univ. of Mississippi Med. Ctr., Dept. of Med., Jackson, Mississippi. Since patients are asked to start therapy at the earliest signs of peritonitis initial home therapy must be sufficiently comprehensive yet nontoxic. We reviewed our peritonitis episodes associated with gram positive dialysate cultures from 1/85 through 7/85. We were searching for the frequency of Cephalothin resistance. There were 45 cultures: 6-S. aureus all sensitive to Cephalothin; 32-S. epidermidis 59% (N=19) resistant to Cephalothin; I-Enterococcus resistant to Cephalothin; 5-Streptococci sp.; and I-Bacillus sp. Thus S. epidermidis is the predominant organism and 44% of the gram positive isolates were Cephalothin resistant. Vancomycin is our drug of choice. All patients recovered using 50 mg/L of Vancomycin added in dialysate and administered in 4 dialysate exchanges/day. Two patients, 60 &63 Kg respectively, also received a 500 mg IV loading dose. After 3 days Vancomycin serum levels were 32 and 40 ug/ml and after 7 days 40 &38 ug/ml, respectively. We measured levels in 4 patients who only received 50 mg/L of dialysate instilled as above. Average patient weight was 81±8 Kg (SEM). Mean serum level after 3 to 7 days was 21±5 ug/ml. These dosage regimens appear to be safe &effective. Due to the frequency of Cephalothin resistance we suggest that Vancomycin be considered one of the drugs of choice for empiric home therapy of peritonitis.

(c

{!

EXTE?.NALLY APPLIED ABDmn~;AL VIBRATION AS A HETHOD FOR n;PEtOVI:;G EFFICIEKCY IN PERITOI';EAL DIALYSIS.

Jacob Rudoy,

~icardo

Kohan and Jackie Ben-Ari. Dept of

::ephrology, Lady Davis Carmel Hospital, Haifa, Israel.

::e studied the effects of externally applied vibrations onto the abdominal wall on the efficiency of peritoneal dialysis (PD). Six patients were studied. 3 manual, consecutive, regular PD exchanges (control

session CS) were compared with vibration session (VS) of same 3 consecutive exchanges with 5 min inflow,

20 min. dwell time and 35 min. drainage.

The VS

vibrations ltJere applied onto the abdominal wall,

during the dwell time only. Vibrations were induced utili~ing a Puritan-Bennett Vibrator-Percussor with a frequency of 5 Hertz and an amplitude of 2 mm.

Samples of blood and dialysate were analyzed for BUS, creatinine (Cr) and potassium (K). Mean clearance (C) ,.,as calculated dividing the sum of mass transfer to the dialysate by plasma values and dwell

time. Results ~]ere anlayzed by paired t and \\,ilkinson test.

Curea in CS was 37.9±9 ml/min and increased to 49.7±1 ml/min (p> 0.001) in VS. CCr in CS was 28.4±4.8 ml/min and increased to 36.7±5 ml/min in VS (p 0.0001). CK was 30.5±7 ml/min in CS and increased to 49.7±1 ml/min in VS (p> 0.001). Volume of dialysate output was 2l66±97 ml in CS exchange and 2205±80.2 in VS (p> 0.05). In conclusion, we found evidence that externally applied vibrations may

>

inprove clearances and volume in patient undergoing PD. Since this is a simple non-invasive procedure, ~le are continuing to explore its clinical possibilities and usefulness.

IMMEDIATE HEMODYNAMIC RESPONSE TO FUROSEMIDE IN PATIENTS LNDERGOING CHRONIC HEMODIAL VSIS. Roland Schmieder, Franz H. Messerli, Jose G.R. deCarvalho, Fred Husserl. Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, LA The beneficial effects of furosemide in patients with congestive heart failure are presumably mediated by vasodilation and depletion of extracellular fluid volume. To evaluate the effect of furosemide upon cardiovascular hemodynamics, we studied ten patients with terminal renal failure undergoing hemodialysis thrice weekly. Arterial pressure, heart rate and cardiac output Ondocyanine green dye) were measured in triplicate, and cardiovascular indices (total peripheral resistance, central blood volume) were calculated by standard formula. Furosemide was gi ven by a bolus injection of 60 mg, and hemodynamics were determined before, 5, 10, 15 and 30 minutes after the injection. Furosemide produced a decrease in central blood volume of -13.::!:.7% from pretreatment values, most pronounced 5 min after the injection, together with a nonsignificant fall in cardiac output (from 6.76.::!:.l.BB to 6.17.::!:.1.65 l/min). Furosemide had no significant effect on arterial pressure, heart rate, stroke volume and total peripheral resistance. All hemodynamic parameters returned to baseline values after 30 minutes. The decrease in central blood volume reflects a redistribution of the total blood volume with a shift from the cardiopulmonary circulation to the periphery indicating dilation of the capacitance vessels. It is concluded that even in patients undergoing hemodialysis furosemide acutely decreases left ventricular preload by venous dilation and therefore could be immediately beneficial in acute volume overload.

MANAGEMENT OF RENAL FAILURE AFTER HEART TRANSPLANTATION. Robert T. Schweizer, Stanley Bartus Henry B.C. Low, Alfredo Nino, James Dougherty and Michael Rossi. Hartford Hospital, Transplantation Service, Depts. of Surgery and Medicine, Hartford, CT Cyclosporine (Cyc) has improved organ transplant (Tx) success, but with occasional nephrotoxicity. Heart Tx recipients are especially prone to acute renal dysfunction (RD) because of pre-Tx and extracorporeal bypass ischemia. The addition of Cyc has increased RD, in part due to more toxic IV Cyc and inadvertant high blood levels due to unexpected excellent absorption of oral Cyc. Rapid reduction of Cyc can lead to severe rejection and death. We therefore added azathioprine (Aza) from the time of Tx, along with Cyc and prednisone (P). In a series of 8 heart Tx recipients, all receiving initial IV Cyc, RD developed in 7. One patient reqUired hemodialysis and 5 were oliguric. Cyc was reduced with concomitant increase in Aza. RD rapidly reversed in all patients. No rejection activity was found on endomyocardial biopsy at day 5, and only 3/7 had mild or moderate rejection at day 10-14 post-Tx, despite variable HLA matches. All rejection episodes were reversed. Two patients had infections, both easily controlled. No tumors have developed. Survival is 100%. Six recipients with mean follow-up of 6m (r=2-lOm) have a current mean serum creatinine of 1.4mg/dl (r=0.9-l.4mg/dl). We conclude that concomitant use of Aza with Cyc and P permits successful and safe immunosuppression despite post-Tx RD. In addition, a lower maintenance dose of Cyc has prevented longer term Cyc nephrotoxicity.

AlB

LYMPHOCYTIC FUNCTION AND STATUS OF HEPATITIS-B ANTIGEN(HB Ag) AND ANTIBODY(HB AG) IN HEMODIALYSIS PATIENTS(P1 S.Shen, R.Welik, S:Zemel, M.Weir,J.Sadler University of Maryland, Baltimore, MD. We investigated the value of lymphocytic function on predicting host responses to either natural hepatitis-B infection (HBI) or Heptavax (HBV) among P. Three doses of 40U9 HBV were given to P with negative HBsAg and HB AB at 0, I ,6 mos. Their sera were tested for HB~Ab ab6ut 3 mos. later. Peripheral blood Iymphocytes(PBU were collected from pre-dialpis blood samples and cultured without and with phytohr~~gglutinin (PHA) in 3 concentrations for 72 hrs. IUDR uptake were used to measure the proliferative responses fo PBL and expressed as counts per minute (CPM). Stimulation index (SI) was calculated by dividing the maximal CPM after PHA culture with minimal CPM without PHA. The maximal CPM and SI were listed in mean~ SE according to P responses to HBI and HBV. P group n CPM SI I. HB Ag carrier 6 6012+2374 20+7 2. HB:Ab(+), no HBV 33 504sfs58 17+2 3. HB Ab(+), HBV 50 6671+594 22+2 4. HB~Ab(-), HBV 38 5962£676 20+2 CPM and S I from each group were compared between each other by t test, and none of them were significantly different. There were no differences on mean age among group 2,3,4. These findings suggest that there is dissociation between PBL responses to mitogen stimulation and P response to either HBI or HBV. We can not predict the efficacy of HBV on P by their PBL responses to PHA stimulation.

*

aMllNED RENAL AND RESPIRA'IDRY FAILURE.

CAN WE IMPOOVE 1HE

m=lS? Keith Sinpsm and Marjorie E.M. Allisco. Renal Unit, Royal Infirmrry, Glasgow, Scotland, U. K. In a 19 rocnth period 14 patients (rrean age 47.5 years) with acute renal failure (ARF) and respiratory failure

requiring ventilatim have been treated C01tinuously in an Intensive Care Unit (leu) for 1-22 clays (rrean 5 clays) with continUJllS, purp driven, volt..rretrically cmtrolled

ultrafiltration (mean UF rate 24Onls/hr) caTl:Jined with 1 hour periods of bicarba1ate haarodialysis (HD) every 6th hour (CUPID). A polysulphone hollow fibre dialyser (Fresenius F6C 1.25Ti ) """ used together with a Fresenius Jl.2I:J:JX; dialysis monitor MUch crntrolled the UF rate and prepared the dialysate. All patients received a crntirru::IJs heparin infusion and the last 10 patients also received a prostacycline infusion at :ng/kg/min. The unlimited potential for fluid reroval by UF allowed N fluids and feeding to be prescribed freely. Vascular access """ by arteriovenous shunt or double or single It.mll1 central venous cannulae. The rrean BP on UF was 116/~ and on HD """ 116/~. M=an serun creatinine fell fran 645.m:>1/L (-209 SIl) on dsy 1 to a stable level of 2ro.Jro1/L (-156 SIl) on dsy 6. Serun urea similarly fell fran 36 to l3rnol/L. Electrolytes including calciun and phosphate were held within the nornal range. Tho patients on CUPID had clinically inportant bleeding episodes but no other rrajor problffiS were encountered. Five patients were discharged hare, 2 left leu but subsequently died in hospital and 7 died in leu. In the period of the s-ruqy 19 other similar patients received crnventional treatment. Three were discharged hare and 16 died in hospital. CUPID provides rretabolic stability in ARF with nornal electrolytes, stable acceptable nitrogencu3 """te levels, blood pressure and fluid balance. It allows optimal intravena.s feeding and rray irrprove prognosis.

PULMONARY INSUFFICIENCY AS A RESULT OF CHRONIC ASPIRATION SECONDARY TO C.A.P.D. THERAPY. SMITH, S., Goldberg, M., Eastern Va. Med. School, Norfolk, Va. C.A.P.D. useful in the tx. of E.S.R.D. patients does have side effects, notably peritonitis. We report a new complication of C.A.P.D.: aspiration induced pulmonary dysfunction. A white female with no previous pulmonary problems presented with persistent cough, shortness of breath, a burning sensation, sour taste, and negative sputum cultures after four yrs. of C.A.P.D. Upper GI revealed marked esophageal reflux. Pulmonary function test revealed marked restrictive disease with decreased vital capacity. No response to medical therapy of reflux resulted in a decision to stop C.A.P.D. hoping to decrease intra-abdominal pressure and stop reflux aspiration damage. During the next 6 mos. on hemodialysis, symptoms improved. Repeat pulmonary function showed less restrictive disease and increased vital capacity. The next patient, a black male on C.A.P.D. for 3 yrs., developed persistent cough and shortness of breath without evidence of pulmonary infection. Chest x-ray revealed interstitial changes and pulmonary function test showed restrictive disease with decreased vital capacity. Upper GI was consistent with reflux. C.A.P.D. was stopped and pulmonary symptoms improved. Pulmonary insufficiency due to hydrothorax has been reported, however to our knowlegde, there has not been a report of longstanding parenchymal changes due to C.A.P.D •• These two cases show increased intra-abdominal pressure from C.A.P.D. can cause reflux aspiration with pulmonary damage. Clinicians dealing with peritoneal dialysis should be aware of this in patients developing cough and shortness of breath.

PERCUTANEOUS ULTRASONIC LITHOTRIPSY OF THE PELVIC "TRANSPLANT KIDNEY. Arthur D. Smith and Jeffrey A Snyder, Division of Urology, Long Island Jewish Medical Center, New Hyde Park, NY Although renal transplant recipients are faring better with the advent of modern technology, subsequent long-term sequelae are encountered with greater frequency. Two episodes of renal lithiasis in a pelvic transplanted kidney treated by endourologic techniques are reported. The patient had ileal conduit diversion, a combined ileostogram and percutaneous nephrostomy puncture gave access to a large staghorn calculus that was subsequently removed by means of ultrasonic lithotripsy. A concomminent upper pole infundibular stenosis was dilated in an antegrade fashion endourologically after passage of a flexible guidewire from the hydrocalyx into the renal pelvis and exiting out the il ea 1 condu it.

A19

STAGHORN CALCULI: THf TREATMENT OF CHOICE. J,ffrey A. Snyder and Arthur D. Smith, Division of Uro ogy, Dept. of Surgery, Long Island Jewish Medical Center, New Hyde Park, NY Eighty consecutive patients presenting with staghorn calculi have been treated either endourologically with percutaneous ultrasonic lithotripsy (60 patients) or by standard anatrophic nephrolithotomy (20 patients). Those patients treated with the endourologic procedure required fewer post-operative days of convalescence, used less narcotic analgesics post-operatively, had reduced total operative time, and had a significantly faster return to their routine daily activities after discharge from the hospital. A comparative analysis of these two surgical modalities is heretofore described. We believe that the percutaneous approach is a better tolerated operation by patients and is a more cost effective method for removal of staghorn calculi.

1A

CONVENTIONAL IMMUNOSUPPRESSION IN MODERN RENAL TRANSPLANTATION. Gregory G. Stanford, Thomas G. Peters, Ashraf Hidayet, and Louis G. Britt. University of Tennessee (UT) Department of Surgery, Memphis, TN. Conventional immunosuppression (CI) has shown steadily improving trends in renal transplantation. Cyclosporine (CYA) therapy has replaced CI in some centers, but questions reqa~ding efficacy, risks, and costs have led others to continue using CI. In the years 1983, and 1984, 104 patients recieved 105 kidney allografts (58 cadaver [CAD] and 47 living donor [LD]) at UT. CI employed azathioprine and prednisone in all cases, and rejection was treated with both methylprednisolone and anti thymocyte globulin. Cumulative actuarial survival methods were used to study all patients and grafts in July of 1985 (follow-up 6-30 months). Patient survival was 95~~ and 92~~ at 6 months and 1 year respectively. Of the eight deaths during follow-up, sudden cardiorespiratory events (4), liver failure (1) and suicide (1) could not be related to immunosuppression. The two cases of infectious death occurred in splenectomized, regrafted patients. Graf~ function survival was 83% and 80% at six months and

one year. The LRD graft survival of 94?~ at both six months and one year was comparatively better than the 7o?~ and 66% observed in CAD grafts. Death from excessive pharmacologic immunosuppression was not evident in this series, and graft functional survival was excellent in the 47 LRD cases. The ultimate graft function in CAD recipients is acceptable and compares favorably with many centers using CVA in cadavertransplantation. We conclude that conventional methods of immunosuppression remain applicable in renal transplantation, especially in LRD circumstances, and in areas where reimbursement procedures for CYA may not be optimum.

C)

DETERMINATION OF PLATELFI'S IN HUMAN URINE USING ThMJNO-PAP TECHNIWE SUITABLE FOR LIGHI' MICROSCOPY AND TRANSMISSION ELECfRON MICROSCOPY. James Stim, Gregory Meyer, Dr. R. Christiansen, and or. R. Novak. University of Illinois, College of Medicine, Departments of Medicine &Pathology, Rockford, Illinois. This preliminary study sought to determine if platelets could be identified in human urine. Urines fixed with glutaraldehyde were cytospun onto albumin-coated slides and sequentially processed with anti-thrombocyte immunoglobulin, link antibody, and a Peroxidase AntiPeroxidase complex. A substrate reacts with the peroxidase to yield a dark red colored reaction product. By post-fixing in 0s04, dehydrating, and embedding with epoxy resin directly from the slide TEM observations can be made. Incubation of buffy coat in urine at room temperature showed specific reaction to platelets even after 10 days incubation with the strongest reaction occurring up to 3 days. About 10% of 50 urine samples screened for sediment and obtained from clinic and hospitalized patients tested positive with platelet-like bodies appearing as cast-like clumps, individual cells, with strong reaction by granular casts. This shows that platelets are present in urine, can be identified, and their significance should be determined.

DONOR SPECIFIC TRANSFUSIONS (051) FOR HAPLOIDENTICAL LIVING RELATED (LRO) TRANSPLANTS USING CYCLOSPORINE (CYA) PRE1REATMENT (PRE-RX) O.R. Steinmuller. A.C. Novick. C. Buszta. S.B. Streem. R.J. Cunningham. Diane Steinhilber. W.E. Braun. Cleveland Clinic Foundation. Cleveland. Ohio. We have attempted a protocol using OST combined with CYA pre-rx in order to prevent sensitization after transfusion. CYA in a dose of 14 mg/kg/day was given orally from the day prior to the initial transfusion until the time of transplant with the dosage adjusted according to blood levels or toxicity. The results were compared to a group of patients who received no pre-rx during the transfusion process and a second group who received Imuran 1-1 1/2 mg/kg/day pre-rx. OST OST OST No Pre-Rx lmuran Pre-Rx CYA Pre-Rx Positive Crossmatch 32% (12/3B) 16% (4/25) 0% (0/9) Graft B8% (23/26) 90% (19/21) 66% (6/9) survival Early rejection was a frequently encountered problem using the protocol of CYA pre-rx. Besides the three patients who lost their graft to rejection. three required the addition of CYA to their immunosuppressive regimen. Only 2 patients had no rejection episodes on conventional therapy. (prednisone. Imuran and ALG). Rejection episodes during the first two months post transfusion were more frequent with CYA pre-rx compared to no pre-rx or Imuran pre-rx (p=.05). Although CYA may prevent sensitization from OST. it may also prevent the beneficial effect of 051 on reducing rejection and improving graft survival.

A20

*

*

EXACERBATION OF POSSIBLE DIALYSIS ENCEPHALOPATHY WITH DEFEROXAMINE. J.Stivelman,*R.Hakim, G.Schulman, S. Kelleher and J.M. Lazarus. Brigham & Women's Hospital, Boston, MA, State NY Univ., Stony Brook, NY. Deferoxamine (DFO) is being increasingly employed to treat aluminum (Al) related osteomalacia, and iron (Fe) overload, with total recommended doses as high as 6 g/per week, administered at the end of a dialysis session. DFO has also been reported to be effective for the treatment of dialysis encephalopathy. A retrospective analysis of 18 patients treated with DFO from 1983-1985 revealed 13 patients with primarily iron Fe overload (transfusion burden of 963 ± 145 mg of Fe/kg and ferritin of 12,253 ± 1968 ug/L) and 5 patients with Al induced osteomalacia. (Pre DFO Al level 79 ± 19 ug/L). Two patients were initiated on DFO because of early symptoms of dialysis encephalopathy, consisting primarily of speech disorders. Baseline Al levels were 210 ug/L in case #1 and 125 ug/L in case #2. Both patients had rapid deterioration of mental status with development of muteness, myoclonus and seizure disorders and eventually died. One other patient, initiated on DFO for aluminum induced osteomalacia and with no neurological deficits also had rapid deterioration of mental status over a period of 6 weeks. It is suggested that dosage of DFO should be lower in patients with suspected dialysis encephalopathy to prevent fu:ther deterioration and mental status and should be glven early during dialysis to prevent acute sustained levels of Al in the interdialytic period.

MORBIDITY, HOSPITALIZATION AIm THE COST OF RELAPSING NEPHROTIC SYNDROOm (RNS) OF CHILDREN. Amir Tejani,

Kishore Phadke, N. Rashid Khawar and Howard Trachtman.

S. U.N. Y., DOImstate Hedical Center, Ne>! York. He reviewed data on 19 children with relapsing

nephrotic syndrome continuously followed at our institution for 2-10 years, in order to determine the

cost of hospitalization and the attendant morbidity of ,,,hat is generally considered a benign disease. All patients were treated with repeated courses of steroids and at least one course of cyclophosphamide, and follOl"ed till Dec. 1984 or up to End Stage Renal Disease status (ESRD). The mean age at onset of 10 females and 9 males was 4.5 years. The mean number of hospitalization was 10.5 (4-29), and the mean number of days spent in hospital was 81.5 (19-239). The mean number of days spent in hospital per patient, per year was 13 (2-46). 85% of admissions were for evacuating the edema with intravenous albumin and lasix and 15% admissions were

for neritonitis.

The total cost of hospitalization

in 1984 dollars was 775,000, with a mean of 40,789 per patient (9500-119000). Additionally a mean of $7,067 cost for outpatient visits was incurred (16.5 visits) per patient. At the end of the review period, 10 patients continue to be proteinuric, 6 are in ESP~ (Dialysis/ Transplant) and 3 are in remission. Our study shows that a high morbidity is attached to the RNS of children and the cost of symptomatic therapy is prohibitive, suggesting that other modalities besides steroids and antimetabolites must be found for controlling the childhood nephrotic syndrome.

SERUM VITAMIN D METABOLITES AND DIETARY INTAKE OF PHQ SPHATE(PlIN PATIENTS WITH EARLY RENAL FAILURE(ERFl ~Llessi1Q[e,A.Venturi,S.Adami,G.Maschio - Istituto di NefroLogia Medica,Universita di VERONA,ItaLia In view of the controversy existing on vit.D met 2 boLites LeveLs in ERF,serum vit.D metaboLites were ~ vaLuated in 41 patients with GFR 30-70 mL/min on free dietary intake of P and during 29! 2 months of Low-P, high-caLcium(Cal diet(7oo mg P,130o-18oo mg Cal. On free diet,serum 1.2SvitD was significantLy reduced (18.8+2.0 vs 29.1+2.3 pg/mL in controLs,p
BETTER ALTERNATIVE Jt.1MUNOSUPPRESSIVE PATHWAYS IN KIDNEY TRANSPLANT PATIENTS TREATED WITH CYCLOSPORINE Luis H. Toledo-Pereyra, Sidney Baskin, Lawrence HcNichol, James Whitten, Vijay r1ittal, Depts. of Surgery and Medicine, t~ount Carmel Mercy Hospital, Detroit, Michigan Since cyclosporine (Cy) became available at our institution in December, 1983, 57 recipients of cadaver renal transplants have been given an initial immunosuppressive regimen of Cy and prednisolone (Pred). Of this group, 25 patients (43%) have su~cessfully retained their orafts without change of lmmunosuppression for up to 18 months. Only 6 of 10 (60%) patients given additional imuran have wor~ing graft: ~t this. time and three of five (60%) patlents recelvlng addltional imuran and ATGam or ALG have currently functioning grafts. Twelve patients were treated for rejection with 7-14 day courses of ALG or ATGam after the failure of the Cy + Pred therapy. In this group 7 grafts (58%) are currently functioning an~ 5 hav~ been lost to irreversible rejection. In 5 patlents glven Solu-medrol for rejection therapy, 4 (30%) are working (1 with additional imuran and 3 with Solu-medrol alone) and one (a third transplant) is not working. There have been 4 deaths in this series (3-Cy+Pred group,and 1-ALG/ATGam conversion group). Overall patient survival was 92.9% and overall graft survival was 78.8%. In summary, although Cy + Pred therapy can provide appropriate protection from rejection in ren~l transplant recipients, alternative immunosuppresslve.pathways are necessary to achieve better graft survlval.

A21

REDUCTION OF ATN IN THE CYCLOSPORINE ERA L.H. Toledo-Pereyra. Dept. of Surgery, r·lount Carmel Mercy Hospita 1, Detroit, t1i chi gan. The potential for nephrotoxic effects from cyclosporine (Cy) administration after renal transplantation led us to compare the incidence of delayed immediate function (ATN) in cadaver renal transplant recipients in the pre-Cy and Cy eras. The incidence of ATN (dialysis requirements in first post-operative week) and 30-day graft function in these two eras for all cadaver donor kidneys transplanted in Michigan* between January 1983 and August 1934 and for all cadaver donor kidneys transplanted between August 1982 and June 1985 at our center is presented below. Sta te -W i de r1CMH 30-day 30-day Era N ATN Function Function N ATN Pre-Cy 206 (59% 64% ~54% 88% < .01 (p < .001 Cy 78% 57 28% 93% 196 35% A significant decrease in the incidence of AT~l was observed in the Cy era as compared to the pre-Cy era. Apparently, cautious administration of low-dose Cy ( ~4-6 mg/kg/day) in the immediate post-transplant period has circumvented the potential nephrotoxic effects of the drug. Other factors which may contribute to reduced ATN include more frequent multiple organ harvesting procedures, less warm ischemia, better preservation techniques and new preservation solutions for safely extending hypothermic storage.

CYCLOSPORINE (CsA) NEPHROTOXICITY IN FISCHER RATS. Regina Verani, Dennis C. Dobyan, and Ruth Ellen Bulger

Dept. of Pathology and Renal Research Lab, The University of Texas Medical School, Houston, TX. CsA has been shown to be nephrotoxic in both human renal transplantation and in experimental animals. Interstitial nephritis has been reported in Fischer

rats after intraperitoneal (IP) CsA. In this present study, 4 (separate) groups of male Fischer rats received 15 daily injections of 15 and 25 (low dose) and 50 and 100 (high dose) mg/kg/day of CsA diluted in cremophor (C) and saline. Control rats received either C + saline or saline alone. Inulin clearances were performed on day 15. The kidneys were subsequently fixed by vascular perfusion for light (LM) and electron microscopy (EM). All but one rat in the high dose groups developed convulsions and motor weakness

-so

dying after 4-7 days of treatment. Necropsy revealed

extensive vacuolization of all segments of the proxim-

al tubules (PT). Vacuolization was also noted after 15 days of drug treatment in the low dose groups (by both LM and EM). Crystalline structures were noted in the cytoplasm of low and high dose CsA-treated rats and in the control rats receiving the C vehicle but they were not seen in rats receiving only saline. No evidence 0f interstitial nephritis was seen. Glomerular filtration

rate (GFR) in the C + saline and saline controls in was 1039+S5 and 106S+4S, respectively (not significantly different). GFR ;as reduced in both low dose groups (703+91 after a 15 mg dose; P
*State-wide data provided by the Transplantation Society of Michigan, Organ Procurement Agency of Michigan, Ann Arbor, Michigan.

does not appear to be a consequence of the C vehicle.

THE VALUE OF THE ONE-HOUR ALLOGRAFT BIOPSY AS A ROUTINE PROCEDURE: STUDY OF 45 CASES. N. Walsh, I. Alexopoulou, D. Ludwin. St. Joseph's

SONE LEAD IN DIALYSIS PATIENTS. Richard P. Wedeen, Patrick D'haese, Gert A. Verpooten, Frank Van de Vyver, Walter G. Visser and Marc E. DeBroe., VAMC, East Orange, NJ, U. Ant\Verp, Wil rijk, Belgium and U. Hosp., Utrecht, Netherlands. Since over 90~ of the body Pb is stored in bone, direct measurement of Pb in bone should provide information similar to chelation tests. We therefore measured [Pb] and [Ca++] in 153 unselected transil iac bone biopsies from dialysis patients and 5 unselected cadavers and performed EDTA tests and bone biopsies in 4 Pb "IOrkers. The Pb:Ca ratio corrects for soft tissue in the biopsy and is more reproducable than the [Pb]. The median transil iac [Pb] in the dialysis patients was 4 ppm and the median Pb:Ca ratio \Vas 0.04xl03 while in the cadavers the mean [Pb] was 5.9 ± 3.1 ppm and the mean Pb:Ca was 0.07 ± 0.03xl03. In 19 dialysis patients with analgesic nephropathy and papillary necrosis, transil iac [Pb] and Pb:Ca values were below the median. In 4 Pb workers, chelatable Pb exceeded 1000 ugm/3 days while iliac crest [Pb] exceeded 12 ppm and Pb:Ca exceeded 0.16xl03. In the 8 dialysis patients with the highest Pb:Ca ratios [Pb] was less than 6 ~pm in 3 although the Pb:Ca ratio exceeded 0.15xl0) in all and bone histomorphometry showed no difference from other dialysis patients. These studies indicate that the iliac Pb:Ca ratio provides an index of cumulative past Pb absorption comparable to the EDTA test and that bone Pb is not usually elevated in dialysis patients. Elevated bone Pb is not associated with unique bone disease in renal failure and interstitial nephritis does not cause excessive bone Pb stores.

Hospital, and McMaster University, Hamilton,

Ontario. The usefulness of the one-hour biopsy as a predictor of outcome in renal allograft trans-

plantation is controversial. Light microscopic, immunofluorescent and ultrastructural studies

have shown conflicting results.

The aim of the

present study was to examine the association

between histological abnormalities in the postanastomotic biopsy and longterm graft survival. Forty-five consecutive renal transplantation cases, were assessed. Follow-up ranged from

IS-30 months. Clinical parameters pertaining both to donor and recipient, methods of graft

preservation and duration of ischemia were noted.

Each one-hour allograft biopsy was reviewed by two pathologists. Thirty-two patients are alive with functioning grafts while 11 returned to dialysis. Five deaths occurred, two unrelated to graft failure. Donor or recipient age, primary renal

pathology, allograft preservation and immunosuppressive therapy did not differ significantly between the failed versus successful transplant group.

No one histological lesion accurately

predicted longterm graft survival. However, the clinician and pathologist did obtain information essential to immediate and long term patient

management.

We conclude that though the one-hour

biopsy does not predict the outcome of a renal allograft it is a useful adjunct to management of transplant patients.

A22

o

o

ACUTt tll-ECTS OF HEMODIALYSIS ON LYMPHOCYTE SUBPOPULATIONS AND MITOGENIC RESPONSE TO PIIA. M. Weir, S. Zemel, S. Shen, R. Wei ik, R. Peppler, C. McRoy, J. Sadler, R. Leavitt. Laboratory of Renal Immunology, Renal Division, and Univ. of MD Cancer Center, Univ. of Maryland Hospital, Baltimore, Maryland. The effect of an acute hemodialysisCAH) on lymphocyte numbers, T-cel I subpopulations, and mitogenic response was determined in 106 patientsCages 19-78)on chronic hemodialysis.Peripheral blood lymphocytes CPBL) isolated by Ficoll-Hypaque immediately before AHCPRE) and immediately thereafterCPOST), were Incubated at 37"for 72 hrs. with 4 different concentrations of PHA.PSol iferationCP) was measured as incorporation of 12 IUdR into DNA. In 77 of 133 oaired PRE and POST samples the maximum P response occured after dialysis. Cmean+SD:5162+4361 vs 9337+5647, ~<.OOll maximum P increased in all age groupsCratio of maximum P of POST to PRE in al I patients: 2.6+4.6 . This was not influenced by age C19-29 yrs: 2.8+5.0 Cn~16); 30-39 yrs: 4.1+6.5Cn~22); 40-49 yrs: 2.4+~.0 Cn~2B); 50-59 yrs: I .9:;::2.6 Cn~34); 60-78 yrs: 2.3~2. 7 Cn~29). Increases in P of >50% C44/133) occurred wi-rh equal frequency in al I age groups.RespondersCthose with >50% increase in P)did not differ from non responders in PRE serum BUNC89.2+20. I vs 89.0+18.4)or creatinine CI9.7+5.6 vs 19.4+5.7).There was no change in total lymphocyte numbersCI .4+0.7 10 6 per ml PRE vs 1.4+0.8 POSTlor total T-cell numberC72~10.6 105 per ml PRE vs 74.3+12.6 POST.However there was a significant increase in the ratio of T-helper cel IsCLeu-3+)to Tsuppressor eel IsCLeu-2+)after AHC2.4+1.0 PRE vs 3.4+ 2. I POST, p". 05) . We conc I ude that AH augments I ym-phocyte mitogenic responses and increases T-helper cel Is in most ESRD patients.

SAFETY AND EFFICACY OF REPEATED LOW DOSE STREPTOKINASE INFUSIONS FOR DECLOTTING HEHODIALYSIS SUBCLAVIAN CATHETERS R. Welik , J. JosselsofL, S. Shen, W. Reed, J. Sadler, Div. of Nephrology, Univ. of MD., Baltimore, MD. Although Streptokinase is used as fibrinolytic therapy to declot hemodialysis subclavian catheters, sensitization has been reported in patients receiving multiple courses of therapy. We retrospectively reviewed our experience with low dose Streptokinase in all patients with recurrent subclavian catheter clotting between 8/82 and 6/85. Of 51 patients with subclavian catheters 13 had at least one clotting episode. Of these, 28 clotting episodes occurred in 9 patients (range 2-6/patients). Streptokinase was infused at a rate of 1,000-2,000 units/hr with a mean duration of 15 hr/patient (range 6-48). Boluses of 1-3000 units of Streptokinase were given prior to infusion in 4 clotting episodes involving 2 patients. Total mean dose was 17,535 units/ exposure range (10,000-60,000). 27/28 (96%) were successfully declotted after Streptokinase therapy. Total culrnulative dose of Streptokinase/patient was 54.555 units (range 24,000-120,000). Seven of eight (87.5%) had no adverse reactions to repeated Streptokinase infusion. One patient developed fever at the end of his second exposure without other sequellae. Streptokinase antibody was tested by immunodiffusion in 6/8 patients and was not detected in any. We conclude that repeated courses of low dose Streptokinase are effective in declotting subclavian catheters used for hemodialysis with minimal risk and, in a limited number of cases apparently does not produce sensitization.

THE BENEFICIAL EFFECT OF PRETRANSPLANT STORED DONOR SPECIFIC BLOOD TRANSFUSIONS (DSBT) ON KIDNEY SURVIVAL IN TWO-HAPLOTYPE (2H) IDENTICAL LIVING RELATED DONOR (LRD) TRANSPLANTS (Tx). J. D. Whelchel, A.G.Diethelm, J.J. Curtis, R.G. Luke, B.O. Barger, E.C. Kouhaut, S.T. Huang, Dept. of Surg. & Med., Univ. of Ala. School of Med., Birmingham, Ala. Donor selection and recipient immune modification appear to play important roles in the improvement in graft survival in one-haplotype (lH) matched LRD renal Tx receiving DSBT. In 1981 our center began a deliberate DSBT protocol in 2H LRD kidney recipients. The allograft survival in this group of 46 consecutive Tx between 1981 and 1984 (Group A) was compared to that experienced in 111 consecutive patients receiving 2H matched LRD kidney Tx from 1969 to 1981 (Group B) without DSBT. Both groups were treated with identical immunosuppressive protocols using Azothioprine and Prednisone. Acturial graft survival of Group A was 98% at 3 years and that of Group B, 89% at 1, 88% at 2 and 3 years post Tx(p=0.06). Rejection episodes occurred in 24% of Group A and 41% of Group B patients (p=0.02). Taken with our previous experience of improved graft survival with DSBT in lH LRD TX despite only a 10% sensitization rate (Transpl. Pro.27:1077, 1985), the current 0 sensitization rate with improved graft survival in 2H LRD Tx suggests that the major effect of stored DSBT on improved graft survival is modification of the recipient's immune response to the donor.

RELATIONSHIP BETWEEN NITROGEN (N) INTAKE, URINARY N EXCRETION Ac'lD RENAL FUNCTION ~IITH UNRESTRICTED DIETS IN HEALTHY VOLUNTEERS. Thomas Wiegmann, Tony Amicangelo, Margaret MacDougall, Univ. of Kansas, Kansas City, KS, and KCVAMC, Kansas City, HO. Dietary intake in 5 men and 5 women (age 31 ± 1.1) was analyzed with prospective food diaries in comparison with urine collections over 3 consecutive days. Creatinine N (Cr), urea N (U), and total N (TN) was determined. Non-urea!l was given by the difference TN- (U+Cr). Fecal N was taken as the difference Diet N - TN (Fe). Diet N ranged from 107 to 377 rug/kg/day (226.9 ± 8.1 mg/kg/day). Results are expressed /kg Bodyweight/day in relation to Diet N (r=correlation coefficient): Variable Nean S.E. r p U mg 148.7 8.1 0.655 0.0005 Cr mg 8.6.3 0.269 N.S. CrCl ml/min 1.8 .07 0.377 0.05 U Cl ml/min .75 .06 0.552 0.005 NUN mg 52.1 4.5 0.684 0.005 Fe mg 35.7 7.16 0.562 0.005 The results confirm an overall effect of protein intake on renal function in free living individuals on unrestricted diets. HOlil7ever, the relationship is weak and almost absent in serial analysis of individual cases. Daily changes of protein intake with unrestricted diets are not reflected predictably in changes of renal function. Our results also indicate significant relationships between diet N and all other elements of N excretion, including NO?;, which is thought to be constant. NUN cannot therefore be calculated as a constant during N balance studies with unrestricted diets that cover a livide range of protein intakes.

A23

RENAL INSUFFICIENCY WITH RESISTANT HYPERTENSION: A FREQUENT CLINICAL PRESENTATION OF ATHEROSCLEROTIC RENAL ARTERY STENOSIS. Daniel J. Hilson, Elizabeth Lytle,* George Plonk,* Vincent D'Souza.* Wake Forest

PHAR"IACOKINETIC DISPOSITION OF ESMOLOL AND ITS :vIAJOR METABOLITE (ASL-8123) IN NORMALS AND PATIENTS WITH END-STAGE RENAL DISEASE (ESRD). Brian Wong, John Flaherty, Greg La Folette, .James Hulse, John Gambertoglio and David Warnock. Schools of Pharmacy &: Medicine, Univ. of Calif. &: VA Med. Ctr., San Francisco, CA, &: Amer. Crit. Care, McGaw Park, IL. The kinetics of esmolol (ESM), an ultra-short acting beta-blocker, and its major metabolite (ASL) were determined in 6 normals (NL) and 12 patients with ESRD on hemodialysis (HD) or peritoneal dialysis (CPD). A 4 hr infusion of 150 ug/kg/min of ESM was given and blood, urine and dialysate were collected over 24-72 hrs. HD was performed in 6 patients 24 hr after receiving ESM. Samples were assayed for ESM and ASL by HPLC. Data were analyzed with a 2 compartment open model for average (Cave) and peak (Cpeak) plasma vallj.es, and half times of disapperance (T1/2). Results (-SD) are as follows:

Medical Center, Departments of Medicine, Surgery and

Radiology, hlinston-Salem, North Carolina.

We have been impressed with the occurrence of renal insufficiency with resistant hypertension in

renal artery stenosis (RAS).

We conducted a retro-

spective review of patients with angiographically

documented RAS, who presented to Wake Forest Medical Center from 1980-83, in an attempt to determine the

frequency of this clinical presentation. Renal insufficiency was defined as a serum creatinine ~ 2mg%,

while resistant hypertension was defined as the failure to normalize blood pressure on a triple drug

antihypertensive regimen. \ole identified 149 patients, 121 with atherosclerotic (ASO) RAS and 28 patients with fibromuscular dysplasia (FMD) and RAS. Fortyfive of the 121 patients (37%) with ASO-RAS had renal insufficiency.

F!1D-RAS.

Renal insufficiency was not noted in

ESMOLOL Cave Tl/2 (ugimI) (min) NL 1.07+0.37 7.3+4.1 HD 0.89+0.47 7.1:;3.2 CPD 0.79-0.52 10.6-6.5

Sixteen patients (13%) with ASO-RAS and

renal insufficiency had resistant hypertension.

Thirteen of the 16 had bilateral RAS, while one patient had unilateral RAS in a solitary kidney. Two other patients had unilateral RAS with underlying renal disease.

Renal artery revasculation was suc-

cessful in improving renal function and blood pressure in 7/9 patients. ?rogressive deterioration in renal function occurred in 4/7 patients treated medically or with angioplasty. This clinical presen-

ASL-8123 Cpeak Tl/2 (ugimI) (h!) 42.8+12.2 4.1-+1.2 76.1+23.9 47.5+10.0 87.1-20.4 42.3-20.0

The kinetics of ESM were not significantly different among the 3 groups. Significant accumulation of ASL is seen in HD and CPD, reflecting delayed renal excretion. CPD clearance of ASL does not appear impressive as evidenced by a similar Tl/2 in CPD versus the interdialytic T1/2 in HD. ASL has very limited beta blocking activity, however these data suggest that accumulation in renal failure is not likely to cause significant cardiovascular effects.

tation was associated with a 50% one year mortality. Renal insufficiency with resistant hypertension is a

common clinical presentation of ASO-RAS, and appears to be associated with bilateral RAS.

EFFECT OF TETRACYCLINE (TCN) SOAKED DACRON FELT (OF) PERITONEAL DIALYSIS (PO) CATHETER CUFFS ON TISSUE INGRO,ITH IN RATS. Robert Wurm, Paul G. Jenkins. Mount Sinai Med. Ctr. and Univ. of Wisconsin Med. Sch., Milwaukee, Wisconsin. TCN is an effective and safe sclerosing ag~nt. We hypothesized that if the OF cuff of a PO catheter were soaked in a TCN solution prior to implantation, it might stimulate more rapid tissue ingrowth, thus lessen the likelihood of early leakage after placement, and permit normal exchange volumes earlier. Standard OF material was glued to silastic catheter tubing and cut into Y, cm lengths. One piece was placed in a sub-q pocket in each flank of anesthetized rats with cuffs first soaked in either saline or varying concentrations of TCN solution. Each rat thus served as its own control. The OF cuffs were examined grossly at 2, 4, 7, 14, and 21 days post implant, in different animals. We found that the more concentrated TCN cuffs had more wound dehiscence and early exudate formation without ingrowth while saline OF showed ingrowth by 4 days. No ingrowth difference was apparent after 7 days. We conclude that TCN soaked OF cuffs on PO catheters do not promote earlier or more vigorous tissue ingrowth and may in fact retard early tissue ingrowth and potentially impair wound healing.

HYPOGLYCEMIA - A CAUSE FOR ABUSIVE BEHVIOR DURnlG HllDDIALYSIS. Melvin Yudis, M.D., Robert A. Sirota, KD., Harold D. Stein, M.D., Dept. of Medicine Abington Memorial Hospital Patient cooperation in center hemodialysis (H.D.) is L
A24

}1ETOCLQPRAmm: (Reglan) INDUCED EXACERBATION OF PARKINSONISM IN i':ND STAGE RENAL DISEASE (ESRD). Helvin Yudis, I1.D., Robert A. Sirota, N.D., Harold D. Stein, M. D., Martin Trichtinger, B. Franklin Diam::md, M.D., Dept. of Nedicine, Abington Nerrorial Hospital, Abington, PA We have recently seen an acute deterioration of extrapyramidal symptoms (Sx) in a Parkinsonian patient with ESRD after therapy with Reglan. His Parkinson's disease had been previously well controlled on L-dopa and carbidopa (Sinanet) therapy. He was given Reglan for emesis that developed after angioaccess surgery. The patient is a 44 year old male with diabetic nephropathy, who has been on chronic herrodialysis for 6 mmths. His Parkinson's disease "-'as well controllEd on Sinemet and Symuetrel. Because of anesis and gastroparesis diabeticorum, Reglan was prescribed at a dose of l~ug t.i.d. Er.~sis ceased but his Par~~­ son's Sx of rigidity and bradykinesia worsened during the next 10 days. No :ill1provement \. .as noted with increased doses of Sinemet and brornocryptine ~ q.i.d. Only \vith discontinuation of the Reglan did his neurologic Sx dramatically L
SYSIDlIC Yt:RSINIOSIS - A CCl-lPLICATI01, IN TilE IRON OL)DIALYSIS ?ATlENT (Dt). ;'Ielvin Yudis, ltD., Hobert A. Sirota, H.D.', Harold D. Stein, l1.D., Dept. of Nedicine, Abington l1em:>rial Hospital, Abington, PA Vie have recently seen a hEmXlialysis pt with chronic Fe OL develop systeoic yersiniosis. Yersinia enterocolitica was cultured from blood. Our Dt did not have GI symptoms but presented instead with chills, fever, generalized myalgia and headaches. Treauilent with Tobramycin was effective in eradicating the infection. Our pt is a 23 year old male with a history of Alpert's disease, r:SRD, on chronic herrodialysis for 8 years who had severe anar.ia requiring 1-2 blood transfusions per m:J:lth over several years. This resulted in an Fe OL state \vith a serum ferritin of 6620. Physical exam revealed hepatospl~galy. Such pts with ci-rronic Fe OL I!laY have a peculiar susceptibility to yersinia infection. Y. enteroco1itica lUIS a reLl3.rkable dependence on Fe for its growth due to its inability to synthesize iroo 'oinding cOElpmmds terr:led siderophores. The sUjJply of Fe in t:-llS OL pt may have encouraged develo~t of extraintestLnal yersinosis. In sumrary we have described a young ma~ on chronic hEm:ldialysis "tro developed systmuc yersiniosis. His multiple blood transfusions over several years with development of Fe OL :nay have predisposed him to Y. enterocolitica infection. The llUIbility of this organism to produce its own Fe binding compound (siderophores) may allow increased susceptibility L1 the Fe OL pt. The increased use of Desferrioxamine - a siderophore - in the treatr,rent of alur;ll.mnn or Fe OL may potentially result in a higher L~cidence vf Yersiniosis L~ the chronic dialysis pt.

RENAL AND ELECTROLYTE CONSEQUENCES OF ANTIHYPERTENSIVE THERAPY WITH DILTIAZINE VS. HYDROCHLOROTHIAIDE. ET Zawada Jr., Univ. of South Dakota School of Medicine, Sioux Falls, SD. The following study was undertaken to determine whether antihypertensive therapy with diltiazem (Dil) would have less renal-electrolyte disturbances than hydrochlorothiazide (HCTZ). 27 essential hypertensive's participated in this randomized, double-blinded study. Those not controlled (140/90 mmHg) after 12 weeks of therapy were unblinded and received both drugs. All patients were treated for 24 weeks. 3 final groups consisted of 11 who received D alone (Gl), 8 who had HCTZ alone (G2), and 8 who received both to achieve control (G3). Serum electrolytes and hormones and electrolytes and hormones were monitored. Supine blood pressure fell from 152+5/97+1 to 142+4/87+3, from 152+2/99+1 to 134+3/88+2~ and-from 151+4/104+3 to 140+5/92+2mmHg in the-3 groups respectivelY~ p(.Ol for alT. G2 had significant increases in serum uric aCid, plasma renin activity, total serum C02 content, and significant decreases in serum potassium and urinary calcium. We conclude that D had comparable efficacy to HCTZ. No hypokalemia, alkalosis, or hyperuricemia was seen with D. Also, combination therapy was effective when either alone was unsuccess ful .

OPTIMAL CYCLOSPORINE A (CSA) TROUGH WHOLE BLOOD LEVEL (WBL) BY HIGH PRESSURE LIQUID CHROMATOGRAPHY (HPLC) IN RENAL TRANSPLANTS TREATED WITH SINGLE DAILY DOSE (SOD). S.Zemel, S.Shen, L.Lesko, M.Weir, A.Kosenko, F.Dagher, F.Bentley. Div. of Nephrology, Pharmacokinetic Laboratory, and Transplant Surgery, Univ. of Maryland Hospital, Baltimore, Maryland. In order to establ ish an optimal range of CSA trough WBL by HPLC in kidney transplant patients, we determined WBL in 55 consecutive renal transplants(49 cadaveric,6 one haplotype matched living related).Patients were given CSA at either 5mg/kg/day IV followed by tapering single oral dose starting at 15mg/ kg/day or oral only at 15 mg/kg/day.The decrements in dose were 1.0mg/kg/day every 1-2 weeks.Blood for trough WBL determinations were drawn before AM CSA dosing once every week for the first 6 mos. fol lowing transplantation.Clinical diagnosis of CSA toxicity(T) or acute rejection(AR)was confirmed either by graft biopsy or responses to management. T or AR was re Iated to CSA WBL determined within one week prior to the event.CI inical correlations of CSA trough WBL and time course post transplantation are I isted below: (* number of episodes with AR/T). CSA WBL 0-1 Mo. 2-4 Mo. 5-6 Mo . .; 100 5/1* 5/1 I/O 100-200 s/O 4/0 0/0 201-300 I/O 0/1 0/1 % % 0/0 301-400 > 400 3/3 0/2 0/3 We conclude that the optimal trough WBL by HPLC is 300-400 ng/m lin the t i rst month, 200-300 Ilg/m lin mos. 2-4, and 100-200 ng/m lin mos. 5-6 in SOD reg imen. Serial monitoring ot CSA WBL is essential tor the prevention of AR and T.

OV:;;PJ.DAD~(Fe

A25