Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study

Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study

Original Investigation Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study Sanjay Kulkarni, Guo Wei, Wei Ji...

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Original Investigation

Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study Sanjay Kulkarni, Guo Wei, Wei Jiang, Licia A. Lopez, Chirag R. Parikh, and Isaac E. Hall Rationale & Objective: There may be important transplant-related differences between right and left kidneys, including logistical/surgical considerations about vessel length for the right compared to the left kidney from the same donor. Because US centers choose between the right and left kidney when their recipient is ranked higher on a “match-run,” we sought to determine whether deceased-donor right kidneys have had worse posttransplantation outcomes than left kidneys. Study Design: Paired Organ Procurement and Transplantation Network analysis. Setting & Participants: Deceased-donor kidney pairs transplanted during 1990 to 2016. Exposure: Right versus left kidney controlling for other significant factors.

Results: 87,112 recipient pairs shared the following donor characteristics: mean age of 41 ± 14 years, 60% males, and 11% with cardiac death. Recipient characteristics were numerically similar by donor kidney side but with some statistical differences given the sample size. Right kidneys had slightly longer cold ischemia time. DGF occurred more often for right kidneys (28% vs 25.8%; P < 0.001; adjusted OR, 1.15 [95% CI, 1.12-1.17]). The adjusted hazard ratio (aHR) for all-cause graft failure with right kidneys within 6 months was 1.07 (95% CI, 1.03-1.11), and was 0.99 (95% CI, 0.97-1.01) thereafter. The aHRs for death-censored graft failure with right kidneys before and after 6 months were 1.11 (95% CI, 1.06-1.16) and 0.96 (95% CI, 0.930.99), respectively; the corresonding aHRs for mortality were 0.99 (95% CI, 0.93-1.04) and 1.00 (95% CI, 0.98-1.03), respectively.

Outcomes: Delayed graft function (DGF), allcause and death-censored graft failure, and mortality.

Limitations: Registry data, different transplant eras, reasons for kidney side unavailable.

Analytical Approach: Multivariable conditional logistic regression for DGF; proportional hazards models (conditional on same donor) for failure/mortality with right kidneys (operationalized as 6-month time-varying coefficients) adjusting for DGF and other confounders.

Conclusions: There is modest association for transplantation of right kidneys with DGF and graft loss within the first 6 months, which is lost beyond this time point. These findings do not support the use of laterality of deceased-donor kidneys as an important factor in organ acceptance decisions.

A

ccurately assessing deceased-donor kidney quality is increasingly important with efforts to decrease unnecessary organ discards. The kidney donor risk index (KDRI), a more granular and continuous measure of quality than the “expanded-criteria” donor designation, is now routinely used. Although more useful than prior measures, KDRI is limited in that much of the variability in survival is not accounted for, with a C statistic of 0.62.1 Thus, other factors, including donor serum creatinine trajectory,2-5 kidney biopsy findings,6,7 and anatomic considerations, likely play influential roles during organ offers. However, a consideration that remains unclear is whether deceased-donor kidney laterality (right vs left) associates with transplant outcomes. The right kidney is about 10 to 50 mm shorter and has about 2 to 10 mL less volume (on average) than the left kidney in the same person.8,9 Although the number of extra vessels and/or ureters likely influences offer acceptance more than slight differences in kidney size, vessel length is also important. The right renal vein is shorter (closer to the vena cava) and described as more fragile than the left,10 which may be the primary reason for the AJKD Vol XX | Iss XX | Month 2019

Complete author and article information provided before references. Correspondence to I.E. Hall ([email protected]) Am J Kidney Dis. XX(XX):111. Published online Month X, XXXX. doi: 10.1053/ j.ajkd.2019.08.018

© 2019 by the National Kidney Foundation, Inc.

left-sided preference in living-donor kidney transplantation. A study of Organ Procurement and Transplantation Network (OPTN) data found that only 14% of US living-donor transplants are right sided and that rightsided living-donor kidney transplantation has small but significantly increased risks for delayed graft function (DGF), acute rejection in the first year, and even graft failure.11 Deceased-donor kidney allocation in the United States allows the surgeon for the recipient designated higher on the match-run to choose either kidney when both are available. A registry study from Australia and New Zealand (ANZDATA) found 46% higher adjusted odds of DGF for right compared with left kidneys from the same deceased donor.12 Although the analysis controlled for several transplant and recipient factors, there was no significant difference in cold ischemia, arguing against one of the proposed mechanisms for increased DGF, that is, that right-sided deceased-donor kidneys require more surgical preparation time compared with left kidneys. The investigators also noted 72% higher adjusted risk for graft failure during the first year for right-sided kidneys.12 1

Original Investigation However, the ANZDATA analysis excluded donors with cardiac determination of death (DCD), which accounts for 18.5% of all US deceased-donor kidney transplants,13 and they did not control for the association between DGF and allograft failure.14 There may also be other differences between countries in terms of donor management and organ preservation practices, organ refusal patterns, and both donor and recipient demographics and comorbid conditions. Thus, we performed a paired kidney analysis using OPTN data to determine whether right-sided deceased-donor kidney transplants have had inferior outcomes compared with left-sided kidneys in the United States. The paired analysis controlled for all other donor factors in that both kidney recipients from the same donor were compared in a stratified (matched by donor) fashion. Methods Study Cohort This study used OPTN data as of March 2018. The OPTN system includes data for all US donors, wait-listed candidates, and transplant recipients, submitted by OPTN members and has been described elsewhere.15 The Health Resources and Services Administration, US Department of Health and Human Services, provides oversight to the activities of the OPTN contractor that supplies data to researchers; currently the United Network for Organ Sharing (UNOS). The study was administratively reviewed by the University of Utah Institutional Review Board and determined exempt from oversight given the use of preexisting, deidentified data. As such, individual-level informed consent was not obtained. The cohort consisted of deceased-donor kidney recipient pairs who underwent transplantation between January 1990 and December 2016 with follow-up through December 2017. Each pair consisted of the right and left kidney recipient from the same donor. We excluded recipient pairs in which at least 1 received a multiorgan transplant (eg, simultaneous pancreas-kidney) or recipient

or donor age younger than 16 years. We calculated KDRI and then mapped each value to the kidney donor profile index (KDPI) relative to all US deceased donors during 2010.1,16 Exposure/Outcome Variables The primary exposure was donor kidney side (right vs left). We described all other donor-level factors, though these were controlled for in paired analyses. We considered cold ischemia (hours) and number of HLA antigen mismatches as transplant-level variables. We calculated quartiles for average transplantation center volume as the number of kidney transplantations (living and deceased) performed at each center between 1999 and 2016 divided by 18 years. DGF is defined as any dialysis in the first week of transplantation. All-cause graft failure is defined as recipient mortality, resumption (initiation for pre-emptive transplantation) of maintenance dialysis, or retransplantation. UNOS supplemented recipient death data through the public Death Master File until the Social Security Act limited the use of protected state death records starting November 2011. Since then, UNOS has used a separate secure verification process to confirm follow-up information about recipient death. Primary nonfunction (PNF) is defined as continued (permanent) dialysis beyond 90 days after transplantation and is a cause of graft failure. Statistical Analysis Descriptive statistics were reported as mean ± standard deviation or median with interquartile range for continuous variables and as frequency and percentage for categorical variables. We compared continuous transplant- and recipient-level variables between the right and left kidneys using t tests or Wilcoxon rank sum tests. We used χ 2 tests to compare categorical variables. We compared the outcomes of DGF, PNF, and UNOSreported patient status at last follow-up (alive, dead, lost to follow-up, or retransplantation) by kidney side through paired χ 2 tests or unadjusted conditional logistic

Kidney-pancreas transplants performed from 1990 to 2016 N = 417,610 Exclusions: 135,601 8171 8923 21,443 6470 20,788 5834 36,156

living kidney transplants pancreas only transplants multi-organ transplants kidney-pancreas transplants dual kidney transplants donors <16 years old recipients <16 years old unpaired kidneys

174,224 kidneys Left kidney recipient N = 87,112

2

Right kidney recipient N = 87,112

Figure 1. Study design and exclusions. Kidney transplant recipients from donors that contributed only 1 kidney were excluded from this study.

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Original Investigation regression (stratified by matched donor kidney pairs). Missing values for categorical variables were not excluded by analyzing them as separate categories. Missing values for continuous variables were excluded from analyses such as calculations for means, standard deviations, and regression coefficients. We performed multivariable paired analyses for the occurrence of DGF through conditional logistic regression and fit multivariable proportional hazards regression models (also stratified by matched donor) to evaluate the outcomes of all-cause graft failure, death-censored graft failure, and mortality. We included all transplant- and recipient-level characteristics in regression models for DGF and then for all-cause graft failure and retained statistically significant covariates (in addition to kidney side and recipient demographics) through backward elimination. Final covariates retained for all-cause graft failure were also used to model death-censored graft failure and mortality. For survival analyses, we analyzed kidney side through time-varying coefficients (ie, before vs beyond 6 months posttransplantation) given the a priori concern regarding early detrimental effects for the right-sided kidney and preliminary evidence for nonproportional hazards during early follow-up. To further address the potential importance of donor kidney side regarding early and long-term allograft failure, as well as potential era effects, we performed secondary analyses with: (1) changing kidney side time-varying coefficients to before versus after 3 months posttransplantation, (2) administrative censoring at 5 years after transplantation, and (3) assessing statistical interaction between kidney side and transplantation date before versus after 2000 on graft and recipient survival. We performed additional secondary analyses for the outcomes length of stay (for the initial hospitalization) and readmissions within the first 6 months. We performed subgroup analyses for all-cause and death-censored graft failure based on DCD status and KDPI < 85% or ≥85%. We also performed exploratory paired χ 2 analyses of the UNOS-reported causes of death-censored graft failure within the first 6 months by kidney side. We considered P<0.05 as statistically significant. All statistical tests were 2 sided and analyzed using SAS, version 9.4, statistical software for Windows (SAS Institute) and STATA, version MP 15 (StataCorp LLC). Results Cohort Figure 1 shows cohort assembly, resulting in 87,112 deceased-donor kidney recipient pairs. Mean donor age was 41 ± 14 years, 60% were male, 74% were white, 11% were DCD, and mean KDPI was 46% ± 26% (Table 1). Recipient characteristics were numerically similar by donor kidney side, though several comparisons were statistically different given the large sample size (Table 2). In terms of potentially clinically meaningful AJKD Vol XX | Iss XX | Month 2019

Table 1. Donor Characteristics Characteristic Age, y Male sex Race White Black Hispanic Asian American Indian/Alaska Native Native Hawaiian/other Pacific Islander Multiracial Unknown Height, cm Weight, kg Body mass index, kg/m2 Cause of death Anoxia Stroke Head trauma CNS tumor Other History of hypertension No Yes Unknown History of diabetes No Yes Unknown History of cigarette use No Yes Unknown HCV seropositive DCD ECD Terminal Scr, mg/dL Terminal eGFR, mL/min/1.73 m2 KDRI KDPI

Value (N = 87,112) 40.5 ± 14.4 51,927 (59.6%) 64,177 (73.7%) 9,834 (11.3%) 10,099 (11.6%) 1,798 (2.1%) 340 (0.4%) 227 (0.3%) 533 (0.6%) 104 (0.1%) 172.4 ± 10.2 80.9 ± 20.2 27.3 ± 6.4 15,753 (18.1%) 34,427 (39.5%) 31,310 (36.0%) 549 (0.6%) 5,012 (5.8%) 54,411 (71.6%) 20,830 (27.4%) 728 (1.0%) 70,671 (93.0%) 4,831 (6.4%) 458 (0.6%) 49,614 (65.3%) 25,295 (33.3%) 1,060 (1.4%) 1,881 (2.5%) 8,603 (11.3%) 13,088 (17.2%) 1.2 ± 1.2 85 ± 33 1.2 [1.0-1.5] 46 ± 26

Note: Values are mean ± standard deviation, median [interquartile range], or count (percent). Abbreviations: CNS, central nervous system; DCD, donation after cardiovascular determination of death; ECD, expanded-criteria donor; eGFR, estimated glomerular filtration rate (by Chronic Kidney Disease Epidemiology Collaboration equation); HCV, hepatitis C virus; KDPI, kidney donor profile index (based on the 2010 scaling factor); KDRI, kidney donor risk index; Scr, serum creatinine.

differences, right-sided kidney recipients were less likely to have received a prior transplant (12.5% vs 13.9%; P < 0.001) but the organs they received had slightly longer average cold ischemia times (19.7 vs 18.7 hours; P < 0.001). Delayed Graft Function More right-sided kidney recipients developed DGF compared with left-sided kidney recipients (28.0% vs 25.8%; unadjusted conditional logistic regression P < 3

Original Investigation Table 2. Recipient and Transplant Characteristics for Left and Right Kidneys

Age, y Male sex Race White Black Asian Multiracial, other, or unknown Body mass index, kg/m2 19-<25 25-<30 ≤19 ≥30 Missing History of diabetes Prior transplant No. of prior kidney transplants 0 1 2 3 4 5 Preemptive transplant Dialysis duration before transplant, y 0-<1 1-<2 2-<3 3-<5 ≥5 Missing History of PVD No Yes Unknown Missing PRA 0% >0%-20% >20%-80% >80% Missing HLA antigen mismatch level 0 1 2 3 4 5 6

Total (N = 174,224) 49.9 ± 13.6 106,793 (61.3%)

Left Kidney (n = 87,112) 49.9 ± 13.6 53,712 (61.7%)

Right Kidney (n = 87,112) 50.0 ± 13.6 53,081 (60.9%)

85,861 (49.3%) 53,055 (30.5%) 8,929 (5.1%) 26,379 (15.1%) 27.3 ± 5.5 56,842 (32.6%) 56,314 (32.3%) 6,610 (3.8%) 49,821 (28.6%) 4,637 (2.7%) 53,645 (30.8%) 23,032 (13.2%)

42,979 (49.3%) 26,686 (30.6%) 4,231 (4.9%) 13,216 (15.2%) 27.5 ± 5.5 27,840 (32.0%) 27,981 (32.1%) 3,217 (3.7%) 25,787 (29.6%) 2,287 (2.6%) 26,902 (30.9%) 12,122 (13.9%)

42,882 (49.2%) 26,369 (30.3%) 4,698 (5.4%) 13,163 (15.1%) 27.2 ± 5.4 29,002 (33.3%) 28,333 (32.5%) 3,393 (3.9%) 24,034 (27.6%) 2,350 (2.7%) 26,743 (30.7%) 10,910 (12.5%)

156,140 (89.6%) 16,571 (9.5%) 1,406 (0.8%) 101 (0.1%) 5 (0.0%) 1 (0.0%) 13,327 (7.6%) 3.93 ± 3.26 19,250 (11.0%) 27,579 (15.8%) 26,285 (15.1%) 38,861 (22.3%) 41,980 (24.1%) 20,269 (11.6%)

77,484 (88.9%) 8,785 (10.1%) 780 (0.9%) 61 (0.1%) 2 (0.0%) 0 (0.0%) 6,656 (7.6%) 3.97 ± 3.31 9,467 (10.9%) 13,655 (15.7%) 13,153 (15.1%) 19,390 (22.3%) 21,332 (24.5%) 10,115 (11.6%)

78,656 (90.3%) 7,786 (8.9%) 626 (0.7%) 40 (0.0%) 3 (0.0%) 1 (0.0%) 6,671 (7.7%) 3.88 ± 3.31 9,783 (11.2%) 13,924 (16.0%) 13,132 (15.1%) 19,471 (22.4%) 20,648 (23.7%) 10,154 (11.7%)

130,671 (75.0%) 8,083 (4.6%) 5,551 (3.2%) 29,919 (17.2%) 0.0 [0.0-14.0] 100,058 (57.4%) 30,382 (17.4%) 21,477 (12.3%) 17,898 (10.3%) 4,409 (2.5%) 3.79 ± 1.68 14,275 (8.21%) 6,832 (3.93%) 11,665 (6.71%) 27,424 (15.77%) 44,908 (25.83%) 46,446 (26.71%) 22,316 (12.84%)

65,245 (74.9%) 4,087 (4.7%) 2,733 (3.1%) 15,047 (17.3%) 0.0 [0.0-17.0] 49,387 (56.7%) 15,224 (17.5%) 10,731 (12.3%) 9,603 (11.0%) 2,167 (2.5%) 3.80 ± 1.67 6,814 (7.84%) 3,277 (3.77%) 6,071 (6.98%) 13,935 (16.03%) 22,401 (25.77%) 23,245 (26.74%) 11,189 (12.87%)

65,426 (75.1%) 3,996 (4.6%) 2,818 (3.2%) 14,872 (17.1%) 0.0 [0.0-13.0] 50,671 (58.2%) 15,158 (17.4%) 10,746 (12.3%) 8,295 (9.5%) 2,242 (2.6%) 3.77 ± 1.70 7,461 (8.58%) 3,555 (4.09%) 5,594 (6.43%) 13,489 (15.52%) 22,507 (25.89%) 23,201 (26.69%) 11,127 (12.80%)

P 0.05 0.002 <0.001

<0.001

0.4 <0.001 <0.001

0.9 0.003

0.3

<0.001

<0.001

(Continued)

0.001; Table 3). Receipt of the right-sided kidney was independently associated with increased odds for DGF, with an adjusted odds ratio (aOR) of 1.15 (95% 4

confidence interval [CI], 1.12-1.17; Table 4). Transplantation at higher-volume centers was associated with decreased DGF risk, with aORs of 0.90 (95% CI, 0.85AJKD Vol XX | Iss XX | Month 2019

Original Investigation Table 2 (Cont'd). Recipient and Transplant Characteristics for Left and Right Kidneys Total (N = 174,224) 52,267 (30.0%) 19.2 ± 9.3 34,562 (19.8%) 44,519 (25.6%) 40,865 (23.5%) 45,619 (26.2%) 8,659 (5.0%) 108.2 ± 70.1 38,045 (21.8%) 45,259 (26.0%) 41,478 (23.8%) 49,442 (28.4%)

Kidney pumped Cold ischemia time, h 0-<12 12-<18 18-<24 ≥24 Missing Center volume, kidney transplantations per y <50 50-<85 85-<145 ≥145

Left Kidney (n = 87,112) 25,984 (29.8%) 18.7 ± 9.2 18,860 (21.7%) 22,761 (26.1%) 20,021 (23.0%) 21,133 (24.3%) 4,337 (5.0%) 107.9 ± 70.2 19,266 (22.1%) 22,580 (25.9%) 20,646 (23.7%) 24,620 (28.3%)

Right Kidney (n = 87,112) 26,283 (30.2%) 19.7 ± 9.3 15,702 (18.0%) 21,758 (25.0%) 20,844 (23.9%) 24,486 (28.1%) 4,322 (5.0%) 108.5 ± 70.1 18,779 (21.6%) 22,679 (26.0%) 20,832 (23.9%) 24,822 (28.5%)

P 0.1 <0.001

0.04

Note: Values are mean ± standard deviation, median [interquartile range], or count (percent). Abbreviations: PRA, panel-reactive antibody; PVD, peripheral vascular disease.

0.96), 0.85 (95% CI, 0.80-0.91), and 0.76 (95% CI, 0.710.81) for centers in quartiles 2, 3, and 4 for volume, respectively, compared with the first quartile. Graft Failure and Mortality Total follow-up was 1,041,954 patient-years, and median all-cause graft survival was 4.9 (interquartile range, 2.08.7) years. A total of 1,565 (1%) recipients experienced PNF, with no significant difference by kidney side using unadjusted conditional logistic regression (P = 0.1; Table 3). All-cause graft failure rates were not significantly different by kidney side overall (paired χ 2 P = 0.7, also see paired Kaplan-Meier curves in Fig 2). Based on UNOSreported patient status at last follow-up, there were no significant differences by kidney side in terms of death, loss to follow-up, or retransplantation (overall paired χ 2 P = 0.6). Using proportional hazards analysis, right-sided kidneys were independently associated with increased risk for allcause graft failure within the first 6 months, with an adjusted hazard ratio (aHR) of 1.07 (95% CI, 1.03-1.11;

Table 5). Beyond 6 months, there was no significantly increased risk for all-cause graft failure for right-sided kidneys (aHR, 0.99; 95% CI, 0.97-1.01). DGF was independently associated with increased risk for all-cause graft failure (aHR, 1.68; 95% CI, 1.63-1.73), whereas transplantation at centers in quartiles 2, 3, and 4 for volume was independently associated with decreased risk for allcause graft failure compared with centers in the lowest quartile (aHRs of 0.90 [95% CI, 0.86-0.94], 0.88 [95% CI, 0.84-0.92], and 0.90 [95% CI, 0.86-0.95], respectively). Using cause-specific hazards models, receipt of the right-sided kidney was independently associated with death-censored graft failure before 6 months (aHR, 1.11; 95% CI, 1.06-1.16), whereas beyond 6 months, the association was with modest protection (aHR, 0.96; 95% CI, 0.93-0.99). DGF was independently associated with 2-fold increased risk for death-censored graft failure (aHR, 2.10; 95% CI, 1.99-2.17). However, right-sided kidneys were not associated with death within (aHR, 0.99; 95% CI, 0.93-1.04) or following (aHR, 1.00; 95% CI, 0.98-1.03)

Table 3. Outcomes for Right and Left Kidneys Outcome No. with DGF No. with PNFb Events per 100 patient-yc All-cause graft failure Death-censored graft failure Patient status at last follow-up Alive Died Lost to follow-up Retransplantation

Left Kidney (n = 87,112) 22,427 (25.8%) 754 (0.87%) 8.68 (8.60-8.76) 4.82 (4.76-4.88) 46,241 22,526 11,935 6,408

(53.1%) (25.9%) (13.7%) (7.3%)

Right Kidney (n = 87,112) 24,348 (28.0%) 811 (0.93%) 8.67 (8.59-8.75) 4.79 (4.73-4.85) 45,986 22,534 11,863 6,728

Pa <0.001 0.2 0.8 0.9 0.6

(52.8%) (25.9%) (13.6%) (7.7%)

Abbreviations: DGF, delayed graft function; PNF, primary nonfunction. a P values using unadjusted conditional logistic regression or paired χ2 analyses. b Defined as death-censored graft failure caused by “primary failure” with reported graft survival less than 6 months. c Values in parentheses are 95% confidence intervals.

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Original Investigation Table 4. Conditional Logistic Regression for Delayed Graft Function Odds Ratio (95% CI) Right kidney Race White Asian Black Multiracial, other, or unknown Body mass index 19-<25 kg/m2 25-<30 kg/m2 ≤19 kg/m2 ≥30 kg/m2 Missing Diabetes Peak PRA 1%-19% 20%-79% ≥80% Missing Zero HLA antigen mismatch 0 1 2 3 4 5 6 Cold ischemia time <12 h 12-<18 h 18-<24 h ≥24 h Missing Center volume Q1 (<50 kidney transplants per y) Q2 (50-<85 kidney transplants per y) Q3 (85-<145 kidney transplants per y) Q4 (≥145 kidney transplants per y)

Unadjusted 1.15 (1.13-1.18)a

Adjusted 1.15 (1.12-1.17)a

1.00 0.91 1.72 1.24

(reference) (0.84-0.99)a (1.65-1.80)a (1.17-1.31)a

1.00 0.98 1.61 1.18

(reference) (0.89-1.07) (1.54-1.69)a (1.11-1.25)a

1.00 1.29 0.89 1.80 1.39 1.36

(reference) (1.23-1.35)a (0.80-0.99)a (1.71-1.90)a (1.24-1.56)a (1.31-1.42)a

1.00 1.27 0.90 1.70 1.41 1.27

(reference) (1.21-1.33)a (0.80-1.00)a (1.61-1.80)a (1.25-1.59)a (1.22-1.32)a

1.00 1.07 1.11 0.79 0.91

(reference) (1.00-1.14)a (1.03-1.19)a (0.69-0.90)a (0.86-0.95)a

1.00 1.11 1.23 0.81 0.91

(reference) (1.04-1.19)a (1.14-1.33)a (0.71-0.93)a (0.86-0.95)a

1.00 1.09 1.12 1.25 1.41 1.53 1.68

(reference) (0.97-1.22) (1.01-1.25)a (1.13-1.38)a (1.28-1.55)a (1.38-1.68)a (1.51-1.87)a

1.00 1.10 1.16 1.26 1.38 1.46 1.58

(reference) (0.97-1.24) (1.04-1.30)a (1.14-1.40)a (1.25-1.53)a (1.31-1.62)a (1.41-1.77)a

1.00 1.22 1.49 2.00 1.16

(reference) (1.15-1.29)a (1.40-1.58)a (1.88-2.14)a (1.05-1.29)a

1.00 1.19 1.47 1.96 1.15

(reference) (1.12-1.26)a (1.38-1.57)a (1.83-2.09)a (1.03-1.28)a

1.00 (reference)

1.00 (reference)

0.91 (0.86-0.97)a

0.90 (0.85-0.96)a

0.89 (0.84-0.95)a

0.85 (0.80-0.91)a

0.78 (0.73-0.82)a

0.76 (0.71-0.81)a

Abbreviations: CI, confidence interval; PRA, panel reactive antibody; Q, quartile. a Statistically significant.

the first 6 months after transplantation. Compared with procedures performed at centers in the lowest volume quartile, transplantation at centers in quartiles 2, 3, or 4 was independently associated with lower risk for death (aHRs of 0.91 [95% CI, 0.87-0.96], 0.88 [95% CI, 0.830.93], and 0.89 [95% CI, 0.84-0.94], respectively). Tables S1 and S2 provide results for all covariates for the outcomes of death-censored graft failure and recipient mortality. 6

Secondary Analyses Altering the time-varying coefficients for kidney side from 6 to 3 months posttransplantation resulted in similar aHRs for all-cause and death-censored graft failure with rightsided kidneys that were not statistically different from the primary analyses (interaction P > 0.05; Tables S3 and S4). Administratively censoring follow-up at 5 years did not significantly change any adjusted risk estimate with right-sided kidneys within or following 6 months posttransplantation for any of the outcomes (interaction P > 0.05; Tables S5-S7). Using mixed-effects linear regression, receipt of the right-sided kidney was not associated with length of stay, with an adjusted β coefficient of 0.061 (95% CI, −0.0860 to 0.2083). Compared with the left kidney, the right kidney from the same donor had nominally lower risk for readmission within 6 months (aOR, 0.93; 95% CI, 0.87-1.00), but this was not statistically significant (P = 0.05). Analyses for interaction between right-sided kidneys within the first 6 months posttransplantation and transplantation date before or after 2000 revealed evidence for effect modification with respect to all-cause graft failure (interaction P = 0.04). Before 2000, there were no significant associations for all-cause graft failure with rightsided kidneys within (aHR, 1.03; 95% CI, 0.98-1.09) or following (aHR, 0.99; 95% CI, 0.96-1.02) the first 6 months after transplantation. In transplantations performed since 2000, right-sided kidneys are independently associated with all-cause graft failure within (aHR, 1.11; 95% CI, 1.05-1.16) but not following (aHR, 0.99; 95% CI, 0.97-1.02) the first 6 months after transplantation (Tables S8 and S9). Subgroup analyses for all-cause graft failure by DCD status and KDPI (cutoff 85%) demonstrated similar results that were not statistically different from the primary analyses (interaction P > 0.05; Tables S10-S13). The reported causes of death-censored graft failure within 6 months posttransplantation by kidney side are provided in Table 6. The sample size for these analyses (1,188 recipient pairs) was smaller than for the primary analyses because only pairs in which at least 1 kidney failed within 6 months for causes other than death were included. Unadjusted conditional logistic regression for the individual causes only revealed a statistically significant difference between right versus left kidney recipient pairs (P = 0.04) for early graft failures reportedly due to acute rejection (22.8% vs 28.7% of the total right vs left death-censored graft failures within the first 6 months).

Discussion In addition to summary metrics such as the KDRI when deciding to accept or decline individual deceased-donor kidney offers, transplantation providers consider many donor factors that are not incorporated into current clinical scores. Such factors include additional medical history, trends in pre-procurement kidney function, biopsy AJKD Vol XX | Iss XX | Month 2019

Original Investigation

All-Cause Graft Failure Survival Probability

1.0

0.8

0.6

0.4

0.2

0.0 0

1000

2000

3000

4000

5000

6000

7000 8000

9000

Days After Transplant

Number at risk 28,816 Left Kidney Right Kidney 28,816

5847 5840

14,981 14,856

495 516

1894 1918

1.00

Figure 2. Kaplan-Meier all-cause survival curves by deceased-donor recipient pairs. Recipients from donors that contributed only 1 kidney were excluded from this study. (Upper panel) Survival out to 9,000 days after transplantation (paired long-rank P = 0.5). (Bottom panel) “Zoomed-in” portion of the survival curve for the first 270 days after transplantation.

information, and especially kidney anatomy in relation to blood vessels. In this large database study, we evaluated paired deceased-donor kidney transplantations to determine whether outcomes have differed between right and left kidneys from the same donors in the United States given the known anatomical differences in vessel lengths, as well as other potential or perceived differences based on kidney side. We found modest increased risk for DGF and graft failure within the first 6 months posttransplantation for right-sided kidneys but no deleterious associations with longer-term patient or graft survival. Although these results involve early clinical considerations when it is possible to accept either kidney from an individual deceased donor, they do not support the use of laterality of deceased-donor kidneys as an important factor in organ acceptance decisions. These findings also do not take away from the fact that all transplantable kidneys should be used to their greatest potential to maximize each gift and the impact of deceased donation overall. To our knowledge, 4 single-center analyses have been published regarding deceased-donor kidney laterality and posttransplantation outcomes.17-20 These studies lacked statistical power to make clear determinations for outcomes or to describe adjusted magnitudes of association. However, in the well-designed paired ANZDATA analysis AJKD Vol XX | Iss XX | Month 2019

All-Cause Graft Failure Survival Probability

0.98

Left Kidney

0.96

0.94

Right Kidney

0.92

0.90

0.88 0

30

60

90

120

150

180

210

240

270

Days After Transplant

conducted by Vacher-Coponat et al,12 investigators found that right-sided deceased-donor kidneys were at increased risk for DGF and graft failure in the first year posttransplantation. It was not clear from the report whether graft failure was death-censored, but similar to the current study, the authors found no difference in patient survival between paired recipients. With the larger OPTN sample size, we found that the magnitudes of association for right-sided kidneys in the United States with regard to DGF (aOR, 1.15) and early allcause graft failure (aHR, 1.07) are substantially lower than were reported with ANZDATA (aOR of 1.46 and aHR of 1.72, respectively). Given our sample size and controlling for the development of DGF, we were also able to detect a slight but statistically significant benefit with right-sided kidneys regarding death-censored graft failure beyond 6 months. These results should be considered in relation to the 68% lower risk for mortality for transplantation over continued dialysis on the waiting list, as reported 20 years ago,21 as well as more recent evidence for 13% to 40% lower mortality risk for certain types of recipients of highKDPI (“lower-quality”) kidneys.22 However, taken together, our findings provide reassurance that there is no clinically meaningful difference in long-term outcomes between kidneys from the same deceased donor in the United States. 7

Original Investigation Table 5. Cox Proportional Hazards Regression for All-Cause Graft Failure

Table 5 (Cont'd). Cox Proportional Hazards Regression for AllCause Graft Failure

Hazard Ratio (95% CI) Unadjusted Right vs left kidney First 6 mo Subsequent time Age, per 1-y older Male sex Race White Asian Black Multiracial, other, or unknown Body mass index 19-<25 kg/m2 25-<30 kg/m2 ≤19 kg/m2 ≥30 kg/m2 Missing Diabetes Cold ischemia time <12 h 12-<18 h 18-<24 h ≥24 h Missing Dialysis duration before transplantation <1 y 1-<2 y 2-<3 y 3-<5 y ≥5 y Missing Primary disease Glomerulonephritis Diabetes Graft failure Hypertension Other or unknown No. of previous transplantations 0 1 ≥2 Preemptive transplant Peripheral vascular disease No Unknown Yes Missing

Hazard Ratio (95% CI)

Adjusted

1.08 0.99 1.01 1.08

(1.04-1.12)a (0.97-1.01) (1.01-1.01)a (1.05-1.10)a

1.07 0.99 1.01 1.05

(1.03-1.11)a (0.97-1.01) (1.01-1.01)a (1.02-1.08)a

1.00 0.69 1.20 0.90

(reference) (0.65-0.74)a (1.16-1.24)a (0.86-0.94)a

1.00 0.68 1.10 0.83

(reference) (0.64-0.73)a (1.06-1.14)a (0.79-0.87)a

1.00 1.08 1.08 1.21 1.08 1.42

(reference) (1.05-1.11)a (1.01-1.15)a (1.17-1.25)a (1.00-1.16)a (1.38-1.46)a

1.00 1.01 1.16 1.08 1.03 1.21

(reference) (0.98-1.05) (1.09-1.24)a (1.04-1.11)a (0.95-1.11) (1.14-1.28)a

1.00 1.05 1.07 1.13 1.09

(reference) (1.01-1.10)a (1.02-1.11)a (1.08-1.18)a (1.02-1.16)a

1.00 1.04 1.03 1.06 1.09

(reference) (1.00-1.09)a (0.98-1.08) (1.01-1.11)a (1.02-1.17)a

1.00 1.17 1.21 1.31 1.43 0.96

(reference) (1.12-1.23)a (1.15-1.27)a (1.25-1.37)a (1.37-1.50)a (0.91-1.01)

1.00 1.13 1.13 1.19 1.28 1.13

(reference) (1.08-1.18)a (1.07-1.18)a (1.13-1.25)a (1.22-1.34)a (1.05-1.21)a

1.00 1.50 1.32 1.19 0.96

(reference) (1.44-1.56)a (1.25-1.40)a (1.15-1.24)a (0.92-1.00)

1.00 1.17 1.14 1.08 0.95

(reference) (1.10-1.25)a (1.07-1.22)a (1.04-1.13)a (0.92-0.99)a

1.00 1.10 1.45 0.69

(reference) (1.06-1.15)a (1.26-1.66)a (0.66-0.73)a

1.00 1.07 1.40 0.81

(reference) (1.01-1.13)a (1.20-1.63)a (0.75-0.88)a

1.00 1.06 1.46 1.24

(reference) (0.98-1.14) (1.37-1.56)a (1.16-1.33)a

1.00 1.05 1.25 1.10

(reference) (0.97-1.13) (1.17-1.33)a (1.02-1.18)a (Continued)

Apart from the reassurance that these findings provide, there are likely anatomical reasons for greater technical challenges with right-sided kidneys that could lead to 8

Peak PRA 0% 1%-19% 20%-79% ≥80% Missing HLA antigen mismatch 0 1 2 3 4 5 6 Center volume Q1 (<50 kidney transplants per y) Q2 (50-<85 kidney transplants per y) Q3 (85-<145 kidney transplants per y) Q4 (≥145 kidney transplants per y DGF

Unadjusted

Adjusted

1.00 1.02 1.12 1.27 0.97

(reference) (0.99-1.06) (1.08-1.17)a (1.21-1.33)a (0.90-1.05)

1.00 1.00 1.10 1.25 1.02

(reference) (0.97-1.04) (1.06-1.15)a (1.18-1.32)a (0.94-1.11)

1.00 1.03 1.02 1.11 1.20 1.25 1.32

(reference) (0.95-1.11) (0.95-1.10) (1.03-1.19)a (1.12-1.28)a (1.17-1.34)a (1.22-1.43)a

1.00 1.02 1.02 1.08 1.15 1.19 1.24

(reference) (0.94-1.11) (0.94-1.10) (1.01-1.16)a (1.08-1.24)a (1.11-1.28)a (1.15-1.34)a

1.00 (reference)

1.00 (reference)

0.90 (0.86-0.94)a

0.90 (0.86-0.94)a

0.88 (0.84-0.92)a

0.88 (0.84-0.92)a

0.88 (0.84-0.92)a

0.90 (0.86-0.95)a

1.82 (1.77-1.88)a

1.68 (1.63-1.73)a

Abbreviations: CI, confidence interval; DGF, delayed graft failure; PRA, panelreactive antibody; Q, quartile. a Statistically significant.

worse outcomes posttransplantation. The shorter right renal vein may be technically harder to implant and increase the risk for bleeding or thrombosis. For example, many centers use deceased-donor vena cava extensions to lengthen the right renal vein,23-25 which takes some time for back-table preparation. In addition, deceased-donor right renal arteries often have limited aortic cuffs due to the proximity of the superior mesenteric artery, and the right renal artery tends to be substantially longer than the right renal vein. These complexities can lead to prolonged anastomosis times, as well as arterial kinking or even vascular malpositioning.10 Although prior analyses have evaluated anastomosis time (also called recipient warm ischemia time),26,27 the OPTN data field was inconsistently recorded by centers using variable definitions until it was ultimately removed from data collection forms in 2015. Nonetheless, total cold ischemia time was significantly prolonged for right-sided kidneys. Receipt of the right kidney was still independently associated with DGF compared with the left kidney from the same donor after adjusting for cold ischemia and other important transplant and recipient factors. Furthermore, a 15% increased risk for DGF could be considered clinically significant given that DGF is associated with graft failure and acute rejection at 41% and 38% increased risk, respectively,14 not to mention increased AJKD Vol XX | Iss XX | Month 2019

Original Investigation Table 6. Reported Causes of Death-Censored Graft Failure Within the First 6 Months of Transplantation by Donor Kidney Side Graft Failure Cause of Graft Failure Hyperacute rejection Acute rejection Primary failure Graft thrombosis Infection Surgical complication Urologic complication Recurrent disease Chronic rejection BK (polyoma) virus Otherb

Left Kidney (n = 4,482) 48 (1.1%) 1,192 (26.6%) 753 (16.8%) 628 (14.0%) 204 (4.6%) 40 (0.9%) 23 (0.5%) 66 (1.0%) 266 (5.9%) 14 (0.3%) 1,248 (27.8%)

Right Kidney (n = 4,998) 59 (1.2%) 1,141 (22.8%) 811 (16.2%) 982 (19.7%) 201 (4.0%) 68 (1.4%) 28 (0.6%) 76 (1.0%) 264 (5.3%) 12 (0.2%) 1,356 (27.1%)

Pa 0.2 0.04 0.2 0.1 0.6 0.9 0.9 0.4 0.5 0.4 0.7

Note: Values shown are number (percent) of the total left or right kidney deathcensored failures reportedly due to each cause. a P values using unadjusted conditional logistic regression with sample size of 1,188 recipient pairs (included only pairs in which at least 1 kidney failed within 6 months for causes other than death). b Other includes missing reported cause of death-censored graft failure within the first 6 months (65 left and 73 right kidney failures).

costs with DGF.28,29 However, it is important to note that despite potential evidence for a causal relationship between DGF and graft failure in a prior analysis,30 we chose to control for DGF in the current study with regard to graft survival because several studies have not demonstrated such associations.31-35 This is particularly relevant in certain clinical scenarios that are strongly linked to DGF, such as DCD or donor acute kidney injury, but DGF in those settings is not associated with graft loss.2,36 Early graft losses are devastating to patients and programs. Although we found that right-sided kidneys had modestly increased risk for all-cause and death-censored graft failure within the first 6 months, there was no significant difference in the reported occurrence of PNF between right and left kidneys from the same donor. Our analyses of the UNOS-reported causes of the graft failures within the first 6 months revealed that surgical complications and graft thrombosis were more often reported for right-sided compared with left-sided kidney failures, though paired results (controlling for the same donor) were not significant. Interestingly, a larger proportion of the early left-sided kidney failures were due to rejection, which was significant using paired analysis. Notably, these exploratory analyses were not adjusted for recipient or other transplant factors or multiple comparisons. Notwithstanding, from a patient-centered perspective, it is imperative to provide context about these complications with regard to their overall small occurrence rates and in relation to the likely much greater risk for death with continued waitlist dialysis if organ offers are declined because of deceased-donor kidney laterality.22,37 This study has several limitations. As a retrospective database study, analyses are limited by the quality of data recorded by OPTN members. Information about reasons AJKD Vol XX | Iss XX | Month 2019

for choosing one kidney over the other was not available. We performed backward selection for other available transplant and recipient characteristics, and while confounding from donor factors was eliminated in paired analyses, residual confounding from recipient or other transplant factors is still possible given the observational study design. The issue of organ discards is an important consideration in transplantation but beyond the scope of this paired analysis in that alternative study designs are needed to control for donor factors to evaluate individual outcomes when only one of the kidneys from donors is transplanted. The study period spanned several years that have seen slow but steady improvements in transplantation outcomes. We therefore performed secondary analyses before and after 2000 and found slight differences with regard to increased risk for right-sided kidneys during the more recent era. Data about renal vessels, anastomosis issues, or surgeon experience were not available; however, we attempted to address issues related to surgical experience and available backup by including transplantation center volume. In conclusion, in this large OPTN study of paired deceased-donor kidney transplants, we have shown that compared with the left kidney, receipt of the right kidney from the same donor was independently associated with DGF, as well as all-cause and death-censored graft failure, within the first 6 months. However, risk was modestly increased for these early outcomes, and there was no association between deceased-donor kidney side and recipient mortality. Our findings allude to the complexity and surgical skill involved with kidney transplantation and the breadth of different considerations that affect clinical decision making during deceased-donor kidney offers. The basic anatomic question of which kidney they will receive from a particular deceased donor may be of interest to some transplant candidates, but given that waiting longer for kidney transplantation generally associates with worse survival,38-40 our findings would not support any decision to refuse a kidney offer based solely on which side of the body it came from. Other anatomical/vascular, histologic, and functional considerations may be issues that teams should spend more time discussing with transplant candidates as opposed to the minimal overall differences between right and left deceased-donor kidneys. Supplementary Material Supplementary File (PDF) Table S1: Cause-specific proportional hazards regression for deathcensored graft failure. Table S2: Cox proportional hazards regression for mortality. Table S3: Cox proportional hazards regression for all-cause graft failure (time-varying coefficient for kidney side changed to 3 months). Table S4: Cause-specific proportional hazards regression for deathcensored graft failure (time-varying coefficient for kidney side changed to 3 months). 9

Original Investigation Table S5: Cox proportional hazards regression for all-cause graft failure (follow-up administratively censored at 5 years). Table S6: Cause-specific proportional hazards regression for deathcensored graft failure (follow-up administratively censored at 5 years). Table S7: Cox proportional hazards regression for mortality (followup administratively censored at 5 years). Table S8: Cox proportional hazards regression for all-cause graft failure (before 2000). Table S9: Cox proportional hazards regression for all-cause graft failure (since 2000). Table S10: Cox proportional hazards regression for all-cause graft failure (donation after neurologic determination of death [non-DCD kidneys]). Table S11: Cox proportional hazards regression for all-cause graft failure (DCD kidneys). Table S12: Cox proportional hazards regression for all-cause graft failure (KDPI < 85%). Table S13: Cox proportional hazards regression for all-cause graft failure (KDPI ≥ 85%).

Article Information Authors’ Full Names and Academic Degrees: Sanjay Kulkarni, MD, Guo Wei, MS, Wei Jiang, MS, Licia A. Lopez, BS, Chirag R. Parikh, MD, PhD, and Isaac E. Hall, MD, MS. Authors’ Affiliations: Section of Organ Transplantation and Immunology, Department of Surgery, Yale University School of Medicine, New Haven, CT (SK); Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT (GW, IEH); Yale University Graduate School of Arts and Sciences, New Haven, CT (WJ); Department of Pediatrics, Native American Research Internship, University of Utah School of Medicine, Salt Lake City, UT (LAL); and Division of Nephrology, Department of Internal Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD (CRP). Address for Correspondence: Isaac E. Hall, MD, MS, University of Utah, Division of Nephrology & Hypertension, 30 North 1900 East, School of Medicine Rm 4R312, Salt Lake City, UT 84132. E-mail: [email protected] Authors’ Contributions: Research idea and study design: IEH; statistical analysis: WJ, GW; data analysis/interpretation: SK, CRP, IEH; literature review: LAL, IEH; supervision or mentorship: CRP, IEH. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Support: This work was funded in part by the Health Resources and Services Administration contract 234-2005-37011C and grants awarded to Dr Hall from the American Heart Association (12FTF12080082) and the National Institutes of Health/National Center for Advancing Translational Sciences (UL1TR002538 and KL2TR002539). The funders did not have a role in study design; data collection, analysis, or reporting; or the decision to submit for publication. Financial Disclosure: The authors declare that they have no relevant financial interests. Disclaimer: The data reported here have been supplied by UNOS as the contractor for the OPTN. The interpretation and reporting of these data in no way should be seen as an official policy of or interpretation by the OPTN or the US government. The content is the responsibility of the authors alone and does not necessarily 10

reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. These organizations were not involved in study design, analysis, interpretation, or manuscript creation. Peer Review: Received February 17, 2019. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form August 10, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD’s procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.

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Original Investigation 15. Dickinson DM, Bryant PC, Williams MC, et al. Transplant data: sources, collection, and caveats. Am J Transplant. 2004;4(suppl 9):13-26. 16. Organ Procurement and Transplantation Network. A Guide to Calculating and Interpreting the Kidney Donor Profile Index (KDPI). 2018. https://optn.transplant.hrsa.gov/media/1512/ guide_to_calculating_interpreting_kdpi.pdf. Accessed February 16, 2019. 17. Lechevallier E, Dussol B, Luccioni A, et al. Posttransplantation acute tubular necrosis: risk factors and implications for graft survival. Am J Kidney Dis. 1998;32(6):984-991. 18. Johnson DW, Mudge DW, Kaisar MO, et al. Deceased donor renal transplantation–does side matter? Nephrol Dial Transplant. 2006;21(9):2583-2588. 19. Salehipour M, Bahador A, Jalaeian H, et al. Comparison of right and left grafts in renal transplantation. Saudi J Kidney Dis Transpl. 2008;19(2):222-226. 20. Phelan PJ, Shields W, O'Kelly P, et al. Left versus right deceased donor renal allograft outcome. Transpl Int. 2009;22(12):1159-1163. 21. Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341(23):1725-1730. 22. Massie AB, Luo X, Chow EK, Alejo JL, Desai NM, Segev DL. Survival benefit of primary deceased donor transplantation with high-KDPI kidneys. Am J Transplant. 2014;14(10):23102316. 23. Janschek EC, Rothe AU, Holzenbein TJ, et al. Anatomic basis of right renal vein extension for cadaveric kidney transplantation. Urology. 2004;63(4):660-664. 24. Baptista-Silva JC, Medina-Pestana JO, Verissimo MJ, Castro MJ, Demuner MS, Signorelli MF. Right renal vein elongation with the inferior vena cava for cadaveric kidney transplants. An old neglected surgical approach. Int Braz J Urol. 2005;31(6):519-525; discussion 525. 25. Santangelo M, Spinosa G, Grassia S, et al. In situ elongation patch in right kidney transplantation. Transplant Proc. 2008;40(6):1871-1872. 26. Ferede AA, Walsh AL, Davis NF, et al. Warm ischemia time at vascular anastomosis is an independent predictor for delayed graft function in kidney transplant recipients. Exp Clin Transplant. 2019; https://doi.org/10.6002/ect.2018.0377. 27. Vinson AJ, Rose C, Kiberd BA, et al. Factors associated with prolonged warm ischemia time among deceased donor kidney transplant recipients. Transplant Direct. 2018;4(5):e342.

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28. Freedland SJ, Shoskes DA. Economic impact of delayed graft function and suboptimal kidneys. Transplant Rev. 1999;13(1): 23-30. 29. Hagenmeyer EG, Haussler B, Hempel E, et al. Resource use and treatment costs after kidney transplantation: impact of demographic factors, comorbidities, and complications. Transplantation. 2004;77(10):1545-1550. 30. Butala NM, Reese PP, Doshi MD, Parikh CR. Is delayed graft function causally associated with long-term outcomes after kidney transplantation? Instrumental variable analysis. Transplantation. 2013;95(8):1008-1014. 31. Troppmann C, Gillingham KJ, Gruessner RW, et al. Delayed graft function in the absence of rejection has no long-term impact. A study of cadaver kidney recipients with good graft function at 1 year after transplantation. Transplantation. 1996;61(9):1331-1337. 32. Marcen R, Orofino L, Pascual J, et al. Delayed graft function does not reduce the survival of renal transplant allografts. Transplantation. 1998;66(4):461-466. 33. Woo YM, Jardine AG, Clark AF, et al. Early graft function and patient survival following cadaveric renal transplantation. Kidney Int. 1999;55(2):692-699. 34. Salvadori M, Rosati A, Bock A, et al. One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study. Transplant Proc. 2003;35(8):2863-2867. 35. Oppenheimer F, Aljama P, Asensio Peinado C, Bustamante Bustamante J, Crespo Albiach JF, Guirado Perich L. The impact of donor age on the results of renal transplantation. Nephrol Dial Transplant. 2004;19(suppl 3):iii11-iii15. 36. Singh RP, Farney AC, Rogers J, et al. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post-transplant outcomes. Clin Transplant. 2011;25(2):255-264. 37. Reese PP, Harhay MN, Abt PL, Levine MH, Halpern SD. New solutions to reduce discard of kidneys donated for transplantation. J Am Soc Nephrol. 2016;27(4):973-980. 38. Meier-Kriesche HU, Port FK, Ojo AO, et al. Effect of waiting time on renal transplant outcome. Kidney Int. 2000;58(3): 1311-1317. 39. Goldfarb-Rumyantzev A, Hurdle JF, Scandling J, et al. Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant. 2005;20(1):167-175. 40. Haller MC, Kainz A, Baer H, Oberbauer R. Dialysis vintage and outcomes after kidney transplantation: a retrospective cohort study. Clin J Am Soc Nephrol. 2017;12(1):122-130.

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