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Importance: Recipient outcomes after kidney transplant from deceased donors who received dialysis prior to kidney donation are not well described., Objective: To compare outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation vs recipients of kidneys from deceased donors who did not undergo dialysis., Design, Setting, and Participants: A retrospective cohort study was conducted including data from 58 US organ procurement organizations on deceased kidney donors and kidney transplant recipients. From 2010 to 2018, 805 donors who underwent dialysis prior to kidney donation were identified. The donors who underwent dialysis prior to kidney donation were matched 1:1 with donors who did not undergo dialysis using a rank-based distance matrix algorithm; 1944 kidney transplant recipients were evaluated., Exposure: Kidney transplants from deceased donors who underwent dialysis prior to kidney donation compared with kidney transplants from deceased donors who did not undergo dialysis., Main Outcomes and Measures: The 4 study outcomes were delayed graft function (defined as receipt of dialysis by the kidney recipient ≤1 week after transplant), all-cause graft failure, death-censored graft failure, and death., Results: From 2010 to 2018, 1.4% of deceased kidney donors (805 of 58 155) underwent dialysis prior to kidney donation. Of these 805 individuals, 523 (65%) donated at least 1 kidney. A total of 969 kidneys (60%) were transplanted and 641 kidneys (40%) were discarded. Among the donors with kidneys transplanted, 514 (mean age, 33 years [SD, 10.8 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) underwent dialysis prior to donation and were matched with 514 (mean age, 33 years [SD, 10.9 years]; 98 had hypertension [19.1%] and 36 had diabetes [7%]) who did not undergo dialysis. Kidney transplants from donors who received dialysis prior to donation (n = 954 kidney recipients) were associated with a higher risk of delayed graft function compared with kidney transplants from donors who did not receive dialysis (n = 990 kidney recipients) (59.2% vs 24.6%, respectively; adjusted odds ratio, 4.17 [95% CI, 3.28-5.29]). The incidence rates did not significantly differ at a median follow-up of 34.1 months for all-cause graft failure (43.1 kidney transplants per 1000 person-years from donors who received dialysis prior to donation vs 46.9 kidney transplants per 1000 person-years from donors who did not receive dialysis; adjusted hazard ratio [HR], 0.90 [95% CI, 0.70-1.15]), for death-censored graft failure (22.5 vs 20.6 per 1000 person-years, respectively; adjusted HR, 1.18 [95% CI, 0.83-1.69]), or for death (24.6 vs 30.8 per 1000 person-years; adjusted HR, 0.76 [95% CI, 0.55-1.04])., Conclusions and Relevance: Compared with receiving a kidney from a deceased donor who did not undergo dialysis, receiving a kidney from a deceased donor who underwent dialysis prior to kidney donation was associated with a significantly higher incidence of delayed graft function, but no significant difference in graft failure or death at follow-up.

Although hypothermic machine perfusion (HMP) is associated with improved kidney graft viability and function, the underlying biological mechanisms are unknown. Untargeted metabolomic profiling may identify potential metabolites and pathways that can help assess allograft viability and contribute to organ preservation. Therefore, in this multicenter study, we measured all detectable metabolites in perfusate collected at the beginning and end of deceased-donor kidney perfusion and evaluated their associations with graft failure. In our cohort of 190 kidney transplants, 33 (17%) had death-censored graft failure over a median follow-up of 5.0 years (IQR 3.0-6.1 years). We identified 553 known metabolites in perfusate and characterized their experimental and biological consistency through duplicate samples and unsupervised clustering. After perfusion-time adjustment and false discovery correction, six metabolites in post-HMP perfusate were significantly associated with death-censored graft failure, including alpha-ketoglutarate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, 1-carboxyethylphenylalanine, and three glycerol-phosphatidylcholines. All six metabolites were associated with an increased risk of graft failure (Hazard Ratio per median absolute deviation range 1.04-1.45). Four of six metabolites also demonstrated significant interaction with donation after cardiac death with notably greater risk in the donation after cardiac death group (Hazard Ratios up to 1.69). Discarded kidneys did not have significantly different levels of any death-censored graft failure-associated metabolites. On interrogation of pathway analysis, production of reactive oxygen species and increased metabolism of fatty acids were upregulated in kidneys that subsequently developed death-censored graft failure. Thus, further understanding the role of these metabolites may inform the HMP process and help improve the objective evaluation of allograft offers, thereby reducing the discard of potentially viable organs., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation., Study Design: Prospective cohort., Setting & Participants: 862 deceased donors for 1,137 kidney recipients at 13 centers., Exposures: We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI., Outcomes: The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year., Analytical Approach: Multivariable Fine-Gray models with death as a competing risk., Results: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA., Limitations: BPAR was ascertained through for-cause biopsies, not surveillance biopsies., Conclusions: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is common in deceased organ donors and is associated with high rates of kidney discard by transplant centers. High discard rates may consequently drive nonprocurement of these kidneys by organ procurement organizations. We aimed to study the relationship between donor AKI and kidney nonprocurement., Methods: Using U.S. registry data, we identified donors with at least one organ recovered from 2008 to 2018. We compared characteristics of donors with no kidneys procured across AKI stages, and used multivariable logistic regression to evaluate the relationship between AKI severity and kidney nonprocurement., Results: Overall 14 543 kidneys from 7620 donors were not procured, among which 93% were from donors with AKI. For 6945 donors with no kidneys procured but an extrarenal organ recovered, most had stage 3 (51%), followed by stage 1 (27%) and stage 2 AKI (15%). Nonprocured stage 3 donors were the youngest and had the lowest Kidney Donor Risk Index of all nonprocured donors. Adjusted odds of kidney nonprocurement were 1.14 (95%CI 1.02-1.27) for stage 1, 1.25 (95%CI 1.12-1.41) for stage 2, and 10.37 (95%CI 9.30-11.56) for stage 3 donors, compared to non-AKI donors. Among donors with minimum creatinine <1.5 mg/dl, stage 2 and 3 AKI were still associated with significantly higher odds of nonprocurement., Conclusions: AKI severity is a strong risk factor for kidney nonprocurement. Efforts to address the organ shortage should focus on encouraging procurement and utilization of kidneys from deceased donors with severe AKI, given the large and rising prevalence of donor AKI and excellent transplant outcomes with these kidneys., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association., Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes., Results: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI., Conclusion: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization., Competing Interests: The authors have declared that no competing interests exist.

Kidney allocation trends from deceased donors with acute kidney injury (AKI) have not been characterized since initial Kidney Donor Profile Index reporting in 2012 and its use under the revised Kidney Allocation System (KAS) in 2014. We conducted a retrospective analysis of US registry data to characterize kidney procurement and discard trends in deceased donors with AKI, defined by ≥50% or ≥0.3 mg/dl (≥4.0 mg/dl or ≥200% for stage 3) increase in terminal serum creatinine from admission. From 2010 to 2020, 172 410 kidneys were procured from 93 341 deceased donors 16 years or older; 34 984 kidneys were discarded (17 559 from AKI donors). The proportion of stage 3 AKI donors doubled from 6% (412/6841) in 2010 to 12% (1365/11493) in 2020. Procurement of stage 3 AKI kidneys increased from 51% (423/824) to 80% (2183/2730). While discard of stage 3 AKI kidneys increased from 41% (175/423) in 2010 to 44% (960/2183) in 2020, this increase was not statistically significant in interrupted time-series analysis following KAS implementation (slope difference -0.41 [-3.22, 2.4], and level change 3.09 [-6.4, 12.6]). In conclusion, the absolute number of stage 3 AKI kidneys transplanted has increased. Ongoing high discard rates of these kidneys suggest opportunities for improved utilization., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment., Methods: In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression., Results: Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age ( P <0.001) and higher BMI ( P =0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM., Conclusions: PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time., Competing Interests: C.R. Parikh reports receiving a consulting fee from and Genfit (Data Safety Monitoring Board) and Renalytix (Advisory Board), and reports receiving grant/research support from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Heart, Lung and Blood Institute (NHLBI). E. Akalin reports receiving a research grant from CareDx and National Institutes of Health (NIH). F.L. Weng reports receiving NIH grant support from the National Institute on Minority Health and Health Disparities (NIMHD) (R01MD00766405). J.S. Bromberg reports receiving grant support from NIH (NIDDK/National Institute of Allergy and Infectious Diseases [NIAID]/NIMHD/NHLBI). M.D. Doshi reports receiving salary support from NIDDK. M.N. Harhay reports receiving NIH grant support from NIDDK (K23DK105207 and R01DK124388) and National Science Foundation (NSF) grant support (award 2035007). P.P. Reese reports epidemiology consulting for VALHeath related to identifying patients with CKD; reports receiving investigator-initiated and collaborative grants from AbbVie and Merck to the University of Pennsylvania to support trials of transplanting organs from donors with hepatitis C into hepatitis C–negative recipients; reports receiving investigator-initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence; and reports being an Associate Editor for American Journal of Kidney Disease. S.G. Mansour reports being supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. S. Mohan reports receiving grant and research support from the NIH (NIDDK/NIAID/NIHMD/NIBIB) and NSF; reports receiving consulting fees from Angion BIomedica; and reports being Deputy Editor, Kidney International Reports. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Background and Objectives: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients., Design, Setting, Participants, & Measurements: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database., Results: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95)., Conclusions: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021&#95;03&#95;10&#95;CJN18101120&#95;final.mp3., (Copyright © 2021 by the American Society of Nephrology.)

Background: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes., Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages., Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF., Conclusions: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation., Competing Interests: S.G.M. supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. P.P.R. supported by epidemiology consulting from COHRDATA related to dialysis outcomes. This study received grant/research support from Merck, CVS and initiated grants from Merck to the University of Pennsylvania to support the THINKER (kidney), USHER (heart), and SHELTER (lung) trials of transplanting organs from donors with Hepatitis C into Hepatitis C negative recipients. It initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence. I.E.H. received NIH grant support from NCATS (UL1TR002538 and KL2TR002539). T.M.E.-A. received grant support from NIDDK and US Department of Veterans Affairs. M.D.D. obtained the salary support from NIDDK. S.M. received grant/research support from NIH (NIDDK/NIAID/NIHMD/NIBIB) and consulting fees from Angion Pharmaceuticals. A.Z.R. received NDAs with Pliant Therapeutics and xMD Diagnostics, advisory board of Escala Therapeutics. C.R.P. received consulting fee from Renalytix and grant/research support from National Institute of Diabetes and Digestion and Kidney Diseases, National Heart, Lung, and Blood Institute and Data Safety and Monitoring Board of Genfit, Abbott. M.N.H. received grant support from NIH/NIDDK. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys., Methods: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI)., Results: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.

There are limited data on the nonprocurement of kidneys from solid organ donors. Analysis of Standard Transplant Analysis and Research files was undertaken on all deceased donors in the United States with at least 1 solid organ recovered. From 2000 to 2018, 21 731 deceased donor kidneys (averaging 1144 kidneys per year) were not procured. No kidneys were procured from 8% of liver donors, 3% of heart donors, and 3% of lung donors. Compared to donors with all kidneys procured, those with none procured were older and more likely obese, black, hypertensive, diabetic, hepatitis C positive, smokers, Public Health Service - Increased Risk designated, deceased after cardiac death, or deceased after cerebrovascular accident. Although these donors had lower quality kidneys (median Kidney Donor Risk Index (interquartile range) 1.9 (1.0) vs 1.2 (0.7)), there was substantial overlap in quality between nonprocured and procured kidneys. Nearly one third of nonprocurements were attributed to donor history. Donors with elevated terminal creatinine likely resulting from acute kidney injury (AKI) had higher odds of kidney nonprocurement. Nonprocurement odds varied widely across Organ Procurement and Transplantation Network regions, with a positive correlation between donor kidney nonprocurements and kidney discards at the donation service area level. These findings suggest current discard rates underestimate the underutilization of deceased donor kidneys and more research is needed to optimize safe procurement and utilization of kidneys from donors with AKI., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Background: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes., Methods: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m., Results: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF., Conclusions: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.

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., Outcomes: Delayed graft function (DGF), all-cause and death-censored graft failure, and mortality., 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., 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, 0.93-0.99), 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., Limitations: Registry data, different transplant eras, reasons for kidney side unavailable., 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., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The shortage of deceased donor kidneys for transplants is an ongoing concern. Prior studies support transplanting kidneys from deceased donors with acute kidney injury (AKI), but those investigations have been subject to selection bias and small sample sizes. Current allocation practices of AKI kidneys in the United States are not well characterized., Objectives: To evaluate the association of deceased donor AKI with recipient graft survival and to characterize recovery and discard practices for AKI kidneys by organ procurement organizations., Design, Setting, and Participants: Registry-based, propensity score-matched cohort study from January 1, 2010, to December 31, 2013, in the United States. The dates of analysis were March 1 to November 1, 2019. From 2010 to 2013, a total of 6832 deceased donors with AKI and 15 310 deceased donors without AKI had at least 1 kidney transplanted. This study used a 1:1, propensity score-matched analysis to match deceased donors with AKI to deceased donors without AKI and investigated outcomes in their corresponding kidney recipients., Exposure: Deceased donor AKI, defined as at least 50% or 0.3-mg/dL increase in terminal serum creatinine level from admission., Main Outcomes and Measures: Recipients were assessed for the time to death-censored graft failure and the following secondary outcomes: delayed graft function, primary nonfunction, and the time to all-cause graft failure., Results: Ninety-eight percent (6722 of 6832) of deceased donors with AKI were matched to deceased donors without AKI. The mean (SD) age of the 13 444 deceased donors was 40.4 (14.4) years, and 63% (8529 of 13 444) were male. A total of 25 323 recipients were analyzed (15 485 [61%] were male), and their mean (SD) age was 52.0 (14.7) years. Recipients were followed up for a median of 5 (interquartile range, 4-6) years. Deceased donor AKI status had no association with death-censored graft failure (hazard ratio, 1.01; 95% CI, 0.95-1.08) or all-cause graft failure (hazard ratio, 0.97; 95% CI, 0.93-1.02). The results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics. More recipients of AKI kidneys developed delayed graft function (29% vs 22%, P < .001). Few recipients (120 of 25 323 [0.5%]) developed primary nonfunction regardless of deceased donor AKI status. Recovery and transplantation of AKI kidneys varied by organ procurement organization; most (39 of 58) had high recovery and high discard of AKI kidneys., Conclusions and Relevance: Deceased donor AKI kidneys transplanted in the study period had recipient graft survival comparable to that of non-AKI kidneys. This study's findings suggest that the transplant community should evaluate whether currently discarded AKI kidneys from donors without substantial comorbidities can be used more effectively.

Background and Objectives: In kidney transplantation, the relative contribution of donor versus other factors on clinical outcomes is unknown. We sought to quantify overall donor effects on transplant outcomes for kidney donations from deceased donors., Design, Setting, Participants, & Measurements: For paired donations from deceased donors resulting in transplants to different recipients, the magnitude of donor effects can be quantified by examining the excess of concordant outcomes within kidney pairs beyond chance concordance. Using data from the Organ Procurement and Transplantation Network between the years 2013 and 2017, we examined concordance measures for delayed graft function, death-censored 1-year graft failure, and death-censored 3-year graft failure. The concordance measures were excess relative risk, excess absolute risk, and the fixation index (where zero is no concordance and one is perfect concordance). We further examined concordance in strata of kidneys with similar values of the Kidney Donor Profile Index, a common metric of organ quality., Results: If the transplant of the kidney mate resulted in delayed graft function, risk for delayed graft function was 19% higher (95% confidence interval [95% CI], 18% to 20%), or 1.76-fold higher (95% CI, 1.73- to 1.80-fold), than baseline. If a kidney graft failed within 1 year, then the kidney mate's risk of failure was 6% higher (95% CI, 4% to 9%), or 2.85-fold higher (95% CI, 2.25- to 3.48-fold), than baseline. For 3-year graft failure, the excess absolute risk was 7% (95% CI, 4% to 10%) but excess relative risk was smaller, 1.91-fold (95% CI, 1.56- to 2.28-fold). Fixation indices were 0.25 for delayed graft function (95% CI, 0.24 to 0.27), 0.07 for 1-year graft failure (95% CI, 0.04 to 0.09), and 0.07 for 3-year graft failure (95% CI, 0.04 to 0.10). Results were similar in strata of kidneys with a similar Kidney Donor Profile Index., Conclusions: Overall results indicated that the donor constitution has small or moderate effect on post-transplant clinical outcomes., (Copyright © 2019 by the American Society of Nephrology.)

Background: Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor HCV-viremia or recipient HCV-serostatus., Methods: We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants., Results: Over time, HCV-seronegative recipients received a rising proportion of HCV-viremic kidneys. During the first quarter of 2019, 200 HCV-viremic kidneys were transplanted into HCV-seronegative recipients, versus 69 into HCV-seropositive recipients, while 105 HCV-viremic kidneys were discarded. The probability of HCV-viremic kidney discard has declined over time. Kidney transplant candidates willing to accept a HCV-seropositive kidney increased from 2936 to 16,809 from during this time period. When transplanted into HCV-seronegative recipients, HCV-viremic kidneys matched to HCV-non-viremic kidneys on predictors of organ quality, except HCV, had similar 1-year eGFR (66.3 versus 67.1 ml/min per 1.73 m 2 , P =0.86). This was despite the much worse kidney donor profile index scores assigned to the HCV-viremic kidneys. Recipient HCV-serostatus was not associated with a clinically meaningful difference in 1-year eGFR (66.5 versus 71.1 ml/min per 1.73 m 2 , P =0.056) after transplantation of HCV-viremic kidneys., Conclusions: By 2019, HCV-seronegative patients received the majority of kidneys transplanted from HCV-viremic donors. Widely used organ quality scores underestimated the quality of HCV-viremic kidneys based on 1-year allograft function. Recipient HCV-serostatus was also not associated with worse short-term allograft function using HCV-viremic kidneys., (Copyright © 2019 by the American Society of Nephrology.)

Background: Accumulating evidence implicates the complement cascade as pathogenically contributing to ischemia-reperfusion injury and delayed graft function (DGF) in human kidney transplant recipients. Building on observations that kidney injury can initiate in the donor before nephrectomy, we tested the hypothesis that anaphylatoxins C3a and C5a in donor urine before transplantation associate with risk of posttransplant injury., Methods: We evaluated the effects of C3a and C5a in donor urine on outcomes of 469 deceased donors and their corresponding 902 kidney recipients in a subset of a prospective cohort study., Results: We found a threefold increase of urinary C5a concentrations in donors with stage 2 and 3 acute kidney injury (AKI) compared donors without AKI (P < 0.001). Donor C5a was higher for the recipients with DGF (defined as dialysis in the first week posttransplant) compared with non-DGF (P = 0.002). In adjusted analyses, C5a remained independently associated with recipient DGF for donors without AKI (relative risk, 1.31; 95% confidence interval, 1.13-1.54). For donors with AKI, however, urinary C5a was not associated with DGF. We observed a trend toward better 12-month allograft function for kidneys from donors with C5a concentrations in the lowest tertile (P = 0.09). Urinary C3a was not associated with donor AKI, recipient DGF, or 12-month allograft function., Conclusions: Urinary C5a correlates with the degree of donor AKI. In the absence of clinical donor AKI, donor urinary C5a concentrations associate with recipient DGF, providing a foundation for testing interventions aimed at preventing DGF within this high-risk patient subgroup.

Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m 2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI., (Copyright © 2018 International Society of Nephrology. All rights reserved.)

Background: Kidney transplant (KT) recipients experience high rates of early (≤30 days) hospital readmission (EHR) after KT, and existing studies provide limited data on modifiable discharge factors that may mitigate EHR risk., Methods: We performed a retrospective cohort study of 468 adult deceased donor KT recipients transplanted between 4/2010 and 11/2013 at 5 United States transplant centers. We fit multivariable mixed effects models to assess the association of two potentially modifiable discharge factors with the probability of EHR after KT: (i) weekend discharge and (ii) days to first scheduled follow-up., Results: Among 468 KT recipients, 38% (n = 178) experienced EHR after KT. In fully adjusted analyses, compared to weekday discharges, KT recipients discharged on the weekend had a 29% lower risk of EHR (adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.41-0.94). Compared to follow-up within 2 days of discharge, KT recipients with follow-up within 3 to 6 days had a 28% higher probability of EHR (aOR 1.28, 95% CI 1.13-1.45)., Conclusions: These findings suggest that clinical decisions related to the timing of discharge and follow-up modify EHR risk after KT, independent of traditional risk factors., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the utility of surface-enhanced Raman scattering (SERS) analysis of urine from deceased donors for prognosis of kidney transplant outcomes. Iodide-modified silver nanoparticles were used as the enabler for sensitive measurements of urine proteins. Principal component analysis (PCA) and linear discriminant analysis (LDA) were employed for the statistical analysis of the SERS data. Thirty urine samples in three classes were analysed. The ATN class consists of donors whose kidneys had acute tubular necrosis (ATN), the most common type of acute kidney injury (AKI) with high risk of poor graft performance in recipients, yet yielded acceptable transplant outcome. The DGF class is comprised of donors whose kidney had delayed graft function (DGF) in recipients. The control class includes donors whose kidneys did not have donor ATN or recipient DGF. We show a sensitivity of more than 90 % in differentiating the ATN class from the DGF and control classes. Our methodology can thus help clinicians choose kidneys in the high-risk ATN category for transplant which would otherwise be discarded. Our research is impactful in that it could serve as a valuable guidance to expand the deceased donor pool to include those perceived as high-risk AKI type based on common urinary biomarkers. Picutre: Scheme of SERS analysis of urine samples from deceased donors for kidney transplant outcome indication., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Ischemia-reperfusion injury (IRI) leading to delayed graft function (DGF), defined by the United Network for Organ Sharing as dialysis in the first week (UNOS-DGF), associates with poor kidney transplant outcomes. Controversies remain, however, about dialysis initiation thresholds and the utility for other criteria to denote less severe IRI, or slow graft function (SGF)., Methods: Multicenter, prospective study of deceased-donor kidney recipients to compare UNOS-DGF to a definition that combines impaired creatinine reduction in the first 48 hours or greater than 1 dialysis session for predicting 12-month estimated glomerular filtration rate (eGFR). We also assessed 10 creatinine and urine output-based SGF definitions relative to 12-month eGFR., Results: In 560 recipients, 215 (38%) had UNOS-DGF, 330 (59%) met the combined definition, 14 (3%) died, and 23 (4%) had death-censored graft failure by 12 months. Both DGF definitions were associated with lower adjusted 12-month eGFR (95% confidence interval)-by 7.3 (3.6-10.9) and 7.4 (3.8-11.0) mL/min per 1.73 m, respectively. Adjusted relative risks for 12-month eGFR less than 30 mL/min per 1.73 m were 1.9 (1.2-3.1) and 2.1 (1.1-3.7), with unadjusted areas under the curve of 0.618 and 0.627, respectively. For SGF definitions, postoperative day (POD) 7 creatinine had the strongest association with 12-month eGFR, and POD5 creatinine and creatinine reduction between POD1 and POD2 demonstrated modest separations in 12-month eGFR., Conclusions: Although UNOS-DGF does not adequately predict 12-month function on its own, our findings do not support changing the definition. Postoperative day 7 creatinine is correlated with 12-month eGFR, but large translational studies are needed to understand the biological link between IRI severity at transplant and longer-term outcomes.

Purpose: Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant., Experimental Design: Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12-18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers., Conclusions and Clinical Relevance: Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Kidneys with "high" Kidney Donor Profile Index (KDPI) are often biopsied and pumped, yet frequently discarded., Methods: In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI of 80 or greater that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities., Results: Donors were categorized by the number of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted (n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all P < 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and first hour renal resistance. Kidney injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and kidney injury molecule-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate or graft failure between groups 1 and 2 (41.5 ± 18 vs 41.4 ± 22 mL/min per 1.73 m; P = 0.97 and 9% vs 10%; P = 0.76)., Conclusions: Kidneys with KDPI of 80 or greater comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI of 80 or greater are viable; however, current tools and urine and perfusate biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI.

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m 2 ) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant., (Copyright © 2017 by the American Society of Nephrology.)

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant., (Copyright © 2016 by the American Society of Nephrology.)

Background and Objectives: Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown., Design, Setting, Participants, & Measurements: The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS., Results: Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92)., Conclusions: OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome., (Copyright © 2016 by the American Society of Nephrology.)

Purpose: Since human urine is the most readily available biofluid whose proteome changes in response to disease, it is a logical sample for identifying protein biomarkers for kidney diseases., Experimental Design: Potential biomarkers were identified by using a multiproteomics workflow to compare urine proteomes of kidney transplant patients with immediate and delayed graft function. Differentially expressed proteins were identified, and corresponding stable isotope labeled internal peptide standards were synthesized for scheduled MRM., Results: The Targeted Urine Proteome Assay (TUPA) was then developed by identifying those peptides for which there were at least two transitions for which interference in a urine matrix across 156 MRM runs was <30%. This resulted in an assay that monitors 224 peptides from 167 quantifiable proteins., Conclusions and Clinical Relevance: TUPA opens the way for using a robust mass spectrometric technology, MRM, for quantifying and validating biomarkers from among 167 urinary proteins. This approach, while developed using differentially expressed urinary proteins from patients with delayed versus immediate graft function after kidney transplant, can be expanded to include differentially expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide a single assay to help diagnose, prognose, and manage many kidney diseases., Competing Interests: Statement The authors declare there are no conflicts of interest., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Given growth in kidney transplant waitlists and discard rates, donor kidney acceptance is an important problem. We used network analysis to examine whether organ procurement organization (OPO) network centrality affects discard and outcomes., Methods: We identified 106,160 deceased donor kidneys recovered for transplant from 2000 to 2010 in Scientific Registry of Transplant Recipients. We constructed the transplant network by year with each OPO representing a node and each kidney-sharing relationship between OPOs representing a directed tie between nodes. Primary exposures were the number of different OPOs to which an OPO has given a kidney or from which an OPO has received a kidney in year preceding procurement year. Primary outcomes were discard, cold-ischemia time, delayed graft function, and 1-year graft loss. We used multivariable regression, restricting analysis to the 50% of OPOs with highest discard and stratifying remaining OPOs by kidney volume. Models controlled for kidney donor risk index, waitlist time, and kidney pumping., Results: An increase in one additional OPO to which a kidney was given by a procuring OPO in a year was associated with 1.4% lower likelihood of discard for a given kidney (odds ratio, 0.986; 95% confidence interval, 0.974-0.998) among OPOs procuring high kidney volume, but 2% higher likelihood of discard (odds ratio, 1.021; 95% confidence interval, 1.006-1.037) among OPOs procuring low kidney volume, with mixed associations with recipient outcomes., Conclusions: Our study highlights the value of network analysis in revealing how broader kidney sharing is associated with levels of organ acceptance. We conclude interventions to promote broader inter-OPO sharing could be developed to reduce discard for a subset of OPOs.

Background and Objectives: The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding associations between AKI and recipient outcomes., Design, Setting, Participants, & Measurements: This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status., Results: Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN (P=0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval [95% CI], 0.9 to 1.43) and a kidney donor risk index-adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys (P=0.02 for the interaction between ATN and DCD on the development of DGF)., Conclusions: Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers.

Background: Although some studies have found an association between delayed graft function (DGF) after kidney transplantation and worse long-term outcomes, a causal relationship remains controversial. We investigated this relationship using an instrumental variables model (IVM), a quasi-randomization technique for drawing causal inferences., Methods: We identified 80,690 adult, deceased-donor, kidney-only transplant recipients from the Scientific Registry of Transplant Recipients between 1997 and 2010. We used cold ischemia time (CIT) as an instrument to test the hypothesis that DGF causes death-censored graft failure and mortality at 1 and 5 years after transplantation, controlling for an array of characteristics known to affect patient and graft survival. We compared our IVM results with a multivariable linear probability model., Results: DGF occurred in 27% of our sample. Graft failure rates at 1 and 5 years were 6% and 22%, respectively, and 1-year and 5-year mortality rates were 5% and 20%, respectively. In the linear probability model, DGF was associated with increased risk of both graft failure and mortality at 1 and 5 years (P<0.001). In the IVM, we found evidence suggesting a causal relationship between DGF and death-censored graft failure at both 1 year (13.5% increase; P<0.001) and 5 years (16.2% increase; P<0.001) and between DGF and mortality at both 1 year (7.1% increase; P<0.001) and 5 years (11.0% increase; P<0.01). Results were robust to exclusion of lower quality as well as pumped kidneys and use of a creatinine-based definition for DGF., Conclusion: Instrumental variables analysis supports a causal relationship between DGF and both graft failure and mortality.

Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death via necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are not well understood. Using a urine proteomic screen in mice, we identified the macrophage-secreted chitinase-like protein Brp-39, the murine protein product of the chitinase 3-like 1 gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death via activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both Chi3l1/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood from allografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.

Background: Accurate and reliable assessment of kidney quality before transplantation is needed to predict recipient outcomes and to optimize management and allocation of the allograft. The aim of this study was to systematically review the published literature on biomarkers in two mediums (the perfusate from deceased-donor kidneys receiving machine perfusion and deceased-donor urine) that were evaluated for their possible association with outcomes after kidney transplantation., Methods: We searched the Ovid Medline and Scopus databases using broad keywords related to deceased-donor biomarkers in kidney transplantation (limited to humans and the English language). Studies were included if they involved deceased-donor kidneys, measured perfusate or urine biomarkers and studied a possible relationship between biomarker concentrations and kidney allograft outcomes. Each included article was assessed for methodological quality., Results: Of 1430 abstracts screened, 29 studies met the inclusion criteria. Of these, 23 were studies of perfusate (16 biomarkers examined) and 6 were studies of urine (18 biomarkers examined). Only 3 studies (two perfusate) met the criteria of 'good' quality and only 12 were published since 2000. Perfusate lactate dehydrogenase, glutathione-S-transferase (GST) and aspartate transaminase were all found to be significantly associated with delayed graft function in a majority of their respective studies (6/9, 4/6 and 2/2 studies, respectively). Urine neutrophil gelatinase-associated lipocalin, GST, Trolox-equivalent antioxidant capacity and kidney injury molecule-1 were found to be significantly associated with allograft outcomes in single studies that examined diverse end points., Conclusion: Higher quality studies are needed to investigate modern kidney injury biomarkers, to validate novel biomarkers in larger donor populations and to determine the incremental predictive value of biomarkers over traditional clinical variables.

Background and Objectives: Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m(2))., Design, Setting, Participants, & Measurements: Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined., Results: Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5-24.0) and 5.5 (1.4-21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%-71%) and 45% (8%-83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome., Conclusions: Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.

Background: Reduced kidney function confers a higher risk of acute kidney injury at the time of an inciting event, such as sepsis. Whether the same is true in those with reduced renal mass from living kidney donation is unknown., Methods: We conducted a population-based matched cohort study of all living kidney donors in the province of Ontario, Canada who underwent donor nephrectomy from 1992 to 2009. We manually reviewed the medical records of these living kidney donors and linked this information to provincial health care databases. Non-donors were selected from the healthiest segment of the general population., Results: There were 2027 donors and 20 270 matched non-donors. The median age was 43 years (interquartile range 34-50) and individuals were followed for a median of 6.6 years (maximum 17.7 years). The primary outcome was acute dialysis during any hospital stay. Reasons for hospitalization included infectious diseases, cardiovascular diseases and hematological malignancies. Only one donor received acute dialysis in follow-up (6.5 events per 100 000 person-years), a rate which was statistically no different than 14 non-donors (9.4 events per 100 000 person-years)., Conclusions: These results are reassuring for the practice of living kidney donation. Longer follow-up of this and other donor cohorts will provide more precise estimates about this risk.

Background: Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation that occurs because of a complex interplay between donor organ quality and the biologic milieu of the recipient. The purpose of the study is to better understand the recipient risk factors leading to DGF., Methods: We performed a retrospective cohort study using United Network for Organ sharing data and identified pairs of primary, adult kidney-only transplants that were procured from the same adult donor with discordant occurrence of DGF (i.e., one kidney of the pair had DGF)., Results: A total of 5382 recipient pairs were analyzed. Recipients with DGF were more likely to be male (67% vs. 59%, P<0.01), African American (36% vs. 27%, P<0.01), obese (30% vs. 19%, P<0.01), diabetic (28% vs. 22%, P<0.01), on maintenance dialysis (92% vs. 83%, P<0.01), and to have longer wait-time (571 vs. 471 days, P<0.01), longer cold ischemia time (22 vs. 20 hr, P<0.01), and donor and recipient size mismatch (32% vs. 24%, P<0.01). Multivariable analyses confirmed these associations and identified panel reactive antibody more than 10% and low center volume as additional risk factors for DGF (odds ratio for panel reactive antibody >10%: 1.17, confidence interval 1.05-1.29, P<0.01; and odds ratio for <83 transplants/year: 1.29, confidence interval 1.17-1.44, P<0.01)., Conclusions: After fully matching for donor factors, many recipient characteristics were noted to be associated with DGF. Better management of modifiable recipient and transplant risk factors such as obesity, wait time, and cold time may help to reduce the occurrence of DGF.

Background: The role of serum cystatin C (Scyc), neutrophil gelatinase-associated lipocalin, and interleukin-18 in predicting early graft function after kidney transplant is poorly defined., Methods: We conducted a multicenter prospective cohort study of deceased-donor kidney transplants. We collected serial blood samples for the first 3 days of transplant and monitored need for dialysis within 1 week and graft function at 3 months after transplant., Results: Among 78 recipients with serum biomarker measurements, 26 had delayed graft function (DGF; hemodialysis within 1 week of transplant). Of those not dialyzed, 29 had slow graft function (serum creatinine [Scr] reduction from transplantation to day 7 <70%), and 23 had immediate graft function (IGF; reduction in Scr ≥70%). Scyc levels were statistically different between groups by the first postoperative day (POD), whereas Scr levels were not. Serum neutrophil gelatinase-associated lipocalin and serum interleukin-18 levels were not different between groups. Scyc on the first POD demonstrated good utility for predicting DGF and non-IGF (DGF or slow graft function) with areas under the receiver-operating characteristic curve of 0.83 and 0.85, respectively. Areas under the receiver-operating characteristic curve for predicting DGF and non-IGF using Scr on the first POD were 0.65 and 0.53, respectively. Substituting Scyc for Scr in a clinical algorithm improved its utility for predicting DGF or non-IGF, with adjusted odds ratios of 2.4 and 3.3 for Scyc levels on the first POD. The change in Scyc during the first POD demonstrated a dose-response relationship with 3-month graft function., Conclusions: Scyc outperforms Scr as a predictor of early graft function after deceased-donor kidney transplant.

Background/aims: Clinical methods to predict allograft function soon after kidney transplantation are ineffective., Methods: We analyzed urine cystatin C (CyC) in a prospective multicenter observational cohort study of deceased-donor kidney transplants to determine its peritransplant excretion pattern, utility for predicting delayed graft function (DGF) and association with 3-month graft function. Serial urine samples were collected for 2 days following transplant and analyzed blindly for CyC. We defined DGF as any hemodialysis in the first week after transplant, slow graft function (SGF) as a serum creatinine reduction < 70% by the first week and immediate graft function (IGF) as a reduction ≥ 70%., Results: Of 91 recipients, 33 had DGF, 34 had SGF and 24 had IGF. Urine CyC/urine creatinine was highest in DGF for all time-points. The area under the curve (95% CI) for predicting DGF at 6 h was 0.69 (0.57-0.81) for urine CyC, 0.74 (0.62-0.86) for urine CyC/urine creatinine and 0.60 (0.45-0.75) for percent change in urine CyC. On the first postoperative day, urine CyC/urine creatinine and percent change in urine CyC were associated with 3-month graft function., Conclusion: Urine CyC on the day after transplant differs between degrees of perioperative graft function and modestly corresponds with 3-month function., (Copyright © 2011 S. Karger AG, Basel.)

Background and Objectives: Ensuring follow-up of living kidney donors (LKDs) is essential to long-term preventive care. We sought information on health insurance status of US LKDs, with particular attention to age, gender, and ethnicity., Design, Setting, Participants, & Measurements: The United Network for Organ Sharing/Organ Procurement Transplantation Network database was queried for associations among age at donation, race, gender, and health insurance status. We studied all US LKDs between July 2004 and September 2006., Results: A total of 10,021 LKDs with known health insurance status were studied, 1765 (18%) of whom lacked health insurance at donation. There were 4852 donors without health insurance information. Younger kidney donors had higher rates of being uninsured (age 18 to 34: 26.2%; age 35 to 49: 15.2%; age 50 to 64: 11.2%; age >65: 3.8%; P < 0.0001), as did men (19.5 versus 16.3% for women; P < 0.0001), and ethnic minorities (white 13.4%, black 21%, Hispanic 35.6%, Asian 26.7%; P < 0.0001)., Conclusions: This study confirms that younger patients, ethnic minorities, and men are less likely to have health insurance when donating a kidney, which could negatively affect adherence to long-term follow-up.

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.

When evaluating a living kidney donor and recipient with a father-child relationship, it may be discovered that the two are not biologically related. We analyzed data from the United Network for Organ Sharing and the Canadian Organ Replacement Registry to determine how frequently this occurs. We surveyed 102 potential donors, recipients, and transplant professionals for their opinion on whether such information should be disclosed to the donor-recipient pair. We communicated with transplant professionals from 13 Canadian centers on current practices for handling this information. In the United States and Canada, the prevalence of father-child living kidney donor-recipient pairs with less than a one-haplotype human leukocyte antigen match (i.e., misattributed paternity) is between 1% and 3%, or approximately 0.25% to 0.5% of all living kidney donations. Opinions about revealing this information were variable: 23% strongly favored disclosure; whereas, 24% were strongly opposed to it. Current practices are variable; some centers disclose this information, whereas others do not. Discovering misattributed paternity in living donation is uncommon but can occur. Opinions on how to deal with this sensitive information are variable. Discussion among transplant professionals will facilitate best practices and policies. Strategies adopted by some centers can be considered.

Background: Delayed graft function (DGF) is a common complication of renal transplantation. The short-term consequences of DGF are well known, but the long-term relationship between DGF and patient and graft survival is controversial in the published literature. We conducted a systematic review and meta-analysis to precisely estimate these relationships., Methods: We performed a literature search for original studies published through March 2007 pertaining to long-term (>6 months) outcomes of DGF. The primary outcome was graft survival. Secondary outcomes were patient survival, acute rejection and kidney function., Results: When compared to patients without DGF, patients with DGF had a 41% increased risk of graft loss (RR 1.41, 95% CI 1.27-1.56) at 3.2 years of follow-up. There was no significant relationship between DGF and patient survival at 5 years (RR 1.14, 95% CI 0.94-1.39). The mean creatinine in the non-DGF group was 1.6 mg/dl. Patients with DGF had a higher mean serum creatinine (0.66 mg/dl, 95% CI 0.57-0.74) compared to patients without DGF at 3.5 years of follow-up. DGF was associated with a 38% relative increase in the risk of acute rejection (RR 1.38, 95% CI 1.29-1.47)., Conclusion: The results of this meta-analysis emphasize and quantify the long-term detrimental association between DGF and important graft outcomes like graft survival, acute rejection and renal function. Efforts to prevent and treat DGF should be aggressively investigated in order to improve graft survival given the deficit in the number of kidney donors.

Background: The term delayed graft function (DGF) is commonly used to describe the need for dialysis after receiving a kidney transplant. DGF increases morbidity after transplantation, prolongs hospitalization and may lead to premature graft failure. Various definitions of DGF are used in the literature without a uniformly accepted technique to identify DGF., Methods: We performed a systematic review of the literature to identify all of the different definitions and diagnostic techniques to identify DGF., Results: We identified 18 unique definitions for DGF and 10 diagnostic techniques to identify DGF., Conclusions: The utilization of heterogeneous clinical criteria to define DGF has certain limitations. It will lead to delayed and sometimes inaccurate diagnosis of DGF. Hence a diagnostic test that identifies DGF reliably and early is necessary. Heterogeneity, in the definitions used for DGF, hinders the evolution of a diagnostic technique to identify DGF, which requires a gold standard definition. We are in need of a new definition that is uniformly accepted across the kidney transplant community. The new definition will be helpful in promoting better communication among transplant professionals and aids in comparing clinical studies of diagnostic techniques to identify DGF and thus may facilitate clinical trials of interventions for the treatment of DGF.

Background: Knowledge of any harm associated with living kidney donation guides informed consent and living donor follow-up. Risk estimates in the literature are variable, and most studies did not use a healthy control group to assess outcomes attributable to donation., Methods: We observed a retrospective cohort using health administrative data for donations which occurred in Ontario, Canada between the years 1993 and 2005. There were a total of 1278 living donors and 6359 healthy adults who acted as a control group. Individuals were followed for a mean of 6.2 years (range, 1-13 years) after donation. The primary outcome was a composite of time to death or first cardiovascular event (myocardial infarction, stroke, angioplasty, and bypass surgery). The secondary outcome was time to a diagnosis of hypertension., Results: There was no significant difference in death or cardiovascular events between donors and controls (1.3% vs. 1.7%; hazard ratio 0.7, 95% confidence interval 0.4-1.2). Donors were more frequently diagnosed with hypertension than controls (16.3% vs. 11.9%, hazard ratio 1.4, 95% confidence interval 1.2-1.7) but were also seen more often by their primary care physicians (median [interquartile range] 3.6 [1.9-6.1] vs. 2.6 [1.4-4.3] visits per person year, P<0.001)., Conclusions: Based on administrative data, the risk of cardiovascular disease was unchanged in the first decade after kidney donation. The observed increase in diagnosed hypertension may be due to nephrectomy or more blood pressure measurements received by donors in follow-up and requires prospective study.

Risks of kidney donation include a poorly characterized risk of late kidney failure. We hypothesized that African Americans (AA) kidney donors were at greater risk for kidney failure. The United Network for Organ Sharing/Organ Procurement Transplantation Network database was searched for patients who previously donated a kidney and were subsequently placed on the kidney transplant waiting list. We then compared the race of donors listed for kidney transplant to the race of all living donors during the same time period. Between 1993 and 2005, 8889 donors (14.3%) were AA and 42,419 (68.1%) were Caucasian. During this same time period, 102 previous kidney donors developed kidney failure and were listed for kidney transplantation. Although AAs comprised 14.3% of all living kidney donors, they constituted 44% of donors reaching the waiting list (P<0.001). These data provide indirect evidence that the risk of kidney failure may be exaggerated in AA donors.

Urinary tract infections (UTIs) are the most common infectious complication following renal transplantation. Previous studies uniformly report that renal transplant recipients develop UTIs more often than the general population, but widely differ on how frequently UTIs occur after transplantation. These studies also disagree on the risk factors associated with developing post-transplant UTIs, as well as the effect that UTIs may have on graft outcomes and patient mortality. We performed a retrospective cohort study including all the adult patients who received a renal transplant at two US transplant centers from January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%) patients developed one or more post-transplant UTIs over a mean follow-up period of 42 months. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68-7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality.