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Introduction: Kidney Allocation System (KAS) was implemented by United Network for Organ Sharing in 2014 to reduce allocation disparities. Research Questions: Outcomes of highly sensitized patients (calculated panel reactive antibody (cPRA) ≥ 97%) before and after KAS were compared to low-risk recipients (cPRA <10%) in the post-KAS era were examined. The impact on racial disparities was determined. Design: This was a retrospective study of national registry data. Two cohorts of adult candidates waitlisted for deceased donor transplantation during 3-year periods before and after KAS were identified. Results: Highly sensitized patients (N = 1238 and 4687) received a deceased donor kidney transplant between January 1, 2011 and December 31, 2013 and between January 1, 2015 and December, 31, 2017. Racial disparity for highly sensitized patients improved, yet remained significant (P < 0.001), with Black patients comprising 40% and 41% of the highly sensitized candidates and 28% and 34% of the recipients pre- and post-KAS. While posttransplant death-censored graft failure for highly sensitized recipients was similar overall, post-KAS was associated with improved graft survival in the first year after transplant (HR 0.56, 95% CI 0.40-0.78). When compared to contemporaneous lowrisk recipients, both death-censored and all-cause graft failure were similar for highly sensitized recipients and was associated with increased risk for death-censored graft failure beyond the first year (HR 1.39, 95% CI 1.11-1.73). Conclusion: The allocation system led to an increase in transplantation in highly sensitized candidates without compromising outcomes. Although KAS has led to more balanced transplant rates between highly sensitized Black and White patients, racial inequalities persist.

Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression., Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome., Results: During a median (interquartile range) follow-up period of 37 (18–56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13–141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence., Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele., (© 2023. The Author(s).)

Background: To address long waitlist times and increase pancreas transplantation, our center has implemented a protocol for long-distance importation of pancreata., Methods: We conducted a retrospective review of pancreas transplantation at our institution from January 1, 2014, the start of our importation program, through September 30, 2021. Outcomes were compared between locally procured grafts and imported grafts, defined as grafts procured greater than 250 nautical miles (NM) from our center., Results: Eighty-one patients underwent pancreas transplantation during the study time period; 19 (23.5%) received imported grafts. There were no significant differences in recipient demographics or type of transplant received. Mean distance of import was 644.2 ± 234.0 NM. Imported grafts were more likely to be from pediatric donors <18 years old (p = .02) and a significantly higher proportion of imported grafts came from donors weighing <30 kg (26.3 vs. 3.2%, p = .007). Cold ischemic time was longer for imported grafts than for local grafts (13.4 ± 2.3 h vs. 9.8 ± 2.2 h, p < .01). There was no significant difference in deaths or graft losses within 90 days or at 1 year between groups., Conclusion: Centers should consider expanding criteria for acceptance of imported pancreata to increase the number of transplants and combat organ nonutilization., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Posttransplant fertility returns quickly, and female recipients of child-bearing age may conceive while on immunosuppression. However, pregnancy after transplantation confers risks to the recipient, transplant, and fetus, including gestational hypertension, preeclampsia, gestational diabetes, transplant dysfunction, preterm labor, and low birthweight infants. Additionally, mycophenolic acid (MPA) products are teratogenic. Literature evidence regarding belatacept, a selective T-cell costimulation blocker, during pregnancy and while breastfeeding is extremely limited. When female transplant recipients on a belatacept-based regimen are desirous of pregnancy or at the time of conception, transplant providers manage the immunosuppression regimen in 1 of 2 ways: (1) switch both belatacept and MPA to a calcineurin inhibitor-based regimen with or without azathioprine, which is the more common practice but requires several modifications, having potential negative outcomes; or (2) only switch MPA to azathioprine while continuing belatacept., Methods: This case series includes 16 pregnancies in 12 recipients with exposure to belatacept throughout pregnancy and while breastfeeding. Patient information was obtained from several sources, including Transplant Pregnancy Registry International, providers at Emory University, and Columbia University, as well as literature review., Results: Pregnancy outcomes included 13 live births and 3 miscarriages. No birth defects or fetal deaths were reported in any of the live births. Seven infants were breastfed while their mothers continued belatacept. Outcomes appear comparable to those documented with the administration of calcineurin inhibitors., Conclusions: This case series provides data supporting the continued administration of belatacept during pregnancy. Additional research will assist in developing better guidelines to counsel female transplant recipients on belatacept desiring to pursue pregnancy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: We wanted to compare glycemic control post pancreas transplantation with newer therapeutic options., Methods: We conducted a retrospective analysis of pancreas transplantation at our institution from January 1, 2008, through September 30, 2021. All patients who underwent pancreatic transplantation were 18 years and older. We compared pre-transplant glycemic control of those patients, whether self-monitoring or continuous glucose monitor to their post-transplant glycemic control. Outcomes were assessed by HgbA1C level at evaluation (eval), pretransplant (pre), within the first 5 months posttransplant (post) and 1 year post transplant (1 year)., Results: One hundred and thirty-four patients underwent pancreas transplantation during the 14-year study period. Overall, 1-year patient and graft survival were 95% and 88%. The mean HgbA1C (%) for eval and pre were 8.5(SD ± 1.7) and 8.3(SD ± 1.7), which was significantly higher than post, and 1 year at 5.1(SD ± .6, p < .01) and 5.2(SD ± .6, p < .01). Of those, 38 patients presented with continuous glucose monitors (CGM) +/- pump. Their mean HgbA1C(%) was 8.2(SD ± 1.5) at eval 8.1(SD ± 1.3). These were also significantly higher than post 5.0(SD ± .6, p < .01), and 1 year 5.1(SD ± .5, p < .01)., Conclusion: Pancreas transplant provides superior glycemic control to continuous glucose monitoring and remains the optimal therapy for appropriately selected patients with diabetes., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Chronic active antibody-mediated rejection (CAAMR) constitutes a dominant form of late allograft failure. Several treatment strategies directed at CAAMR have been attempted but proven ineffective at delaying kidney function decline or reducing donor-specific antibodies (DSA). We describe our single-center experience using tocilizumab in patients with CAAMR., Methods: This is a retrospective analysis using electronic medical records. 38 kidney transplant recipients at Columbia University Irving Medical Center who had been prescribed tocilizumab and followed for at least 3 months between August 2013 through December 2019 were included., Results: Tocilizumab use was associated with a decrease in the rate of estimated glomerular filtration rate (eGFR) decline in the 6 months following treatment initiation as compared to the 3 months before tocilizumab was initiated (difference between slopes before and after initiation of treatment = 2.6 mL/min/1.73 m 2 (SE = .8, p = .002) per month for up to 6 months following Tocilizumab initiation). Allograft biopsies showed significant improvement in interstitial inflammation scores (score 1(0,1) to 0 (0,1), p = .03) while other histologic scores remained stable. There was no significant change in proteinuria or DSA titers post-treatment with tocilizumab., Conclusions: Treatment of CAAMR with tocilizumab was associated with a decrease in the rate of eGFR decline and a reduction in interstitial inflammation scores in patients with CAAMR., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Neutropenia is common after kidney transplant. There are few data on febrile neutropenia episodes (FNE) after kidney transplant. We studied FNE in a single-center retrospective cohort of 1682 kidney transplant recipients. Neutropenia (absolute neutrophil count [ANC] <1000) occurred in 32% and FNE in 3%. There were 56 FNE. Median time to FNE was 143 days, and median time from onset of neutropenia to onset of FNE was 5.5 days. The most common sources of infection were urine, blood, and lungs, and in 20% of FNE no source was identified. No infectious organism was identified in 46% of FNE, and opportunistic infections were uncommon. Patient survival was similar among those with and without FNE, but FNE was associated with increased death-censored graft failure (DCGF). Following FNE, acute rejection occurred in 31% and DCGF in 15%, often in the setting of persistent reduced immunosuppression. In conclusion, FNE are common after kidney transplant and are associated with inferior long-term outcomes., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

HIV transmission via solid organ transplant is a rare but serious complication. Here, we describe long-term outcomes in a case of living donor-derived transmission of HIV in a kidney transplant recipient. After 11 years since transplant surgery, the donor shows no evidence of abnormal renal function, while the recipient continues to have a functioning graft. HIV is well controlled in both individuals. This single case report highlights the possibility of acceptable long-term outcomes in living kidney donors with HIV as well as in donor-derived HIV transmission to kidney transplant recipients., (© 2021 Wiley Periodicals LLC.)

Background: Dapone and atovaquone are therapeutic options for PJP prophylaxis in renal transplant recipients. The objective of this study was to evaluate the incidence of anemia in renal transplant recipients receiving these agents., Methods: This is an IRB-approved, retrospective analysis of adult renal transplant recipients who received either dapsone or atovaquone. The primary endpoint was the change in hemoglobin within 90 days of drug initiation. Other endpoints of interest included incidence and management of anemia at multiple time points post-transplant. Categorical variables were compared with Pearson's chi-squared or Fischer's exact test and continuous data were compared utilizing Wilcoxon rank-sum test. Statistical analyses were performed using Stata 14.2., Results: A total of 478 patients were screened for inclusion; 50 patients were evaluated in both the dapsone and atovaquone groups. In the dapsone and atovaquone groups, the median age was 52 and 50.5 years, 44% and 42% were Caucasian, and median time to treatment initiation was 27 and 39 days post-transplant, respectively. All patients receiving dapsone had normal G6PD function. There was no difference in baseline hemoglobin between groups (9.7 g/dL vs 9.8 g/dL, P = .83). The median nadir hemoglobin values were 8.6 g/dL and 9.6 g/dL in the dapsone and atovaquone groups, respectively (P = .047). The median decrease in hemoglobin from baseline to nadir was 1.3 g/dL in dapsone patients and 0.2 g/dL in atovaquone patients (P = .001). Dapsone was discontinued in 46% of patients, whereas atovaquone was discontinued in 18% (P = .001)., Conclusion: Among renal transplant recipients with normal G6PD activity, dapsone is associated with greater hemoglobin reductions and rates of drug discontinuation as compared to atovaquone., (© 2020 Wiley Periodicals LLC.)

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.)

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients., (© 2020 Wiley Periodicals LLC.)

Prolonged warm (WIT) and cold (CIT) ischemia times are often important considerations in the discard of DCD kidneys, but their impact on post-transplant outcomes in the post-KAS era is unclear. We examined the association of ischemia time on delayed graft function (DGF) and death-censored graft failure for DCD kidneys. The 2018 SRTR SAF was utilized to identify post-KAS DCD kidney transplants occurring from 2015 to 2018. Relative risk and Cox regression were used to calculate risk of delayed graft function and hazard of death-censored graft failure, respectively. We identified 4,680 kidneys from DCD donors transplanted from 2015 to 2018 with recorded WIT and CIT times. Median WIT was 21.0 minutes (IQR 14.0-28.0), and CIT was 18.5 hours (IQR 13.9-23.5). The overall incidence of DGF was 42.7%. In a univariable relative risk regression model, extended CIT (24-30 hours:RR 1.37, 95% CI 1.15-1.77; >30 hours:RR 1.47, 95% CI 1.22-1.77) and WIT (20-40 minutes:RR 1.10, 95% CI 1.03-1.17) were associated with increased risk of DGF. When included in a multivariable model, neither prolonged CIT nor WIT were significantly associated with death-censored graft failure. Prolonged WIT and CIT are associated with increased DGF but not death-censored graft failure in recipients of DCD kidney transplants in the post-KAS era. Extended ischemia alone should not be used as a basis for discard or non-utilization of these organs., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy., Methods: We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying "suboptimal" histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification., Results: A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge ( r 2  = 0.11) and core ( r 2  = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04-1.22)., Conclusions: Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background and Objectives: Actionable genetic findings have implications for care of patients with kidney disease, and genetic testing is an emerging tool in nephrology practice. However, there are scarce data regarding best practices for return of results and clinical application of actionable genetic findings for kidney patients., Design, Setting, Participants, & Measurements: We developed a return of results workflow in collaborations with clinicians for the retrospective recontact of adult nephrology patients who had been recruited into a biobank research study for exome sequencing and were identified to have medically actionable genetic findings., Results: Using this workflow, we attempted to recontact a diverse pilot cohort of 104 nephrology research participants with actionable genetic findings, encompassing 34 different monogenic etiologies of nephropathy and five single-gene disorders recommended by the American College of Medical Genetics and Genomics for return as medically actionable secondary findings. We successfully recontacted 64 (62%) participants and returned results to 41 (39%) individuals. In each case, the genetic diagnosis had meaningful implications for the patients' nephrology care. Through implementation efforts and qualitative interviews with providers, we identified over 20 key challenges associated with returning results to study participants, and found that physician knowledge gaps in genomics was a recurrent theme. We iteratively addressed these challenges to yield an optimized workflow, which included standardized consultation notes with tailored management recommendations, monthly educational conferences on core topics in genomics, and a curated list of expert clinicians for patients requiring extranephrologic referrals., Conclusions: Developing the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020&#95;04&#95;16&#95;12481019.mp3., (Copyright © 2020 by the American Society of Nephrology.)

Background and Objectives: Unfavorable histology on procurement biopsies is the most common reason for deceased donor kidney discard. We sought to assess the reproducibility of procurement biopsy findings., Design, Setting, Participants, & Measurements: We compiled a continuous cohort of deceased donor kidneys transplanted at our institution from 1/1/2006 to 12/31/2016 that had at least one procurement biopsy performed, and excluded cases with missing biopsy reports and those used in multiorgan transplants. Suboptimal histology was defined as the presence of advanced sclerosis in greater than or equal to one biopsy compartment (glomeruli, tubules/interstitium, vessels). We calculated κ coefficients to assess agreement in optimal versus suboptimal classification between sequential biopsy reports for kidneys that underwent multiple procurement biopsies and used time-to-event analysis to evaluate the association between first versus second biopsies and patient and allograft survival., Results: Of the 1011 kidneys included in our cohort, 606 (60%) had multiple procurement biopsies; 98% had first biopsy performed at another organ procurement organization and their second biopsy performed locally. Categorical agreement was highest for vascular disease ( κ =0.17) followed by interstitial fibrosis and tubular atrophy ( κ =0.12) and glomerulosclerosis ( κ =0.12). Overall histologic agreement (optimal versus suboptimal) was κ =0.15. First biopsy histology had no association with allograft survival in unadjusted or adjusted analyses. However, second biopsy optimal histology was associated with a higher probability of death-censored allograft survival, even after adjusting for donor and recipient factors (adjusted hazard ratio, 0.50; 95% confidence interval, 0.34 to 0.75; P =0.001)., Conclusions: Deceased donor kidneys that underwent multiple procurement biopsies often displayed substantial differences in histologic categorization in sequential biopsies, and there was no association between first biopsy findings and post-transplant outcomes., (Copyright © 2020 by the American Society of Nephrology.)

Introduction: The Kidney Allocation System in the United States prioritizes candidates with Estimated Post-Transplant Survival (EPTS) ≤20% to receive deceased donor kidneys with Kidney Donor Profile Index (KDPI) ≤20%., Research Question: We compared access to KDPI ≤ 20% kidneys for EPTS ≤ 20% candidates across the United States to determine whether geographic disparities in access to these low KDPI kidneys exist., Design: We identified all incident adult deceased donor kidney candidates wait-listed January 1, 2015, to March 31, 2018, using United Network for Organ Sharing data. We calculated the proportion of candidates transplanted, final EPTS, and KDPI of transplanted kidneys for candidates listed with EPTS ≤ 20% versus >20%. We compared the odds of receiving a KDPI ≤ 20% deceased donor kidney for EPTS ≤ 20% candidates across regions using logistic regression., Results: Among 121 069 deceased donor kidney candidates, 28.5% had listing EPTS ≤ 20%. Of these, 16.1% received deceased donor kidney transplants (candidates listed EPTS > 20%: 17.1% transplanted) and 12.3% lost EPTS ≤ 20% status. Only 49.4% of transplanted EPTS ≤ 20% candidates received a KDPI ≤ 20% kidney, and 48.3% of KDPI ≤ 20% kidneys went to recipients with EPTS > 20% at the time of transplantation. Odds of receiving a KDPI ≤ 20% kidney were highest in region 6 and lowest in region 9 (odds ratio 0.19 [0.13 to 0.28]). The ratio of KDPI ≤ 20% donors per EPTS ≤ 20% candidate and likelihood of KDPI ≤ 20% transplantation were strongly correlated ( r 2 = 0.84)., Discussion: Marked geographic variation in the likelihood of receiving a KDPI ≤ 20% deceased donor kidney among transplanted EPTS ≤ 20% candidates exists and is related to differences in organ availability within allocation borders. Policy changes to improve organ sharing are needed to improve equity in access to low KDPI kidneys.

Objective: We sought to describe a technique for ultra-low-contrast angiography (ULCA) in patients with advanced chronic kidney disease (CKD) and previous coronary artery bypass surgery (CABG)., Background: Patients with advanced CKD and previous CABG are at high risk of developing contrast-induced nephropathy (CIN) because of the additional contrast often required to identify bypass grafts. Apart from hydration, reduced contrast administration is the only established method to minimize the risk of CIN., Patients and Methods: Ten patients underwent ULCA, whereby an intracoronary injection of saline and coronary guidewires were used instead of test injections of contrast for engagement of bypass grafts with catheters. Estimated glomerular filtration rate (eGFR) before and 30 days following angiography were recorded as was the need for renal replacement therapy 1 year after the procedure., Results: All patients completed a diagnostic angiogram without complications. The median volume of contrast delivered was 13.5 ml (interquartile range: 10.5-17.8). The median eGFR was 18.3 ml/min/1.73 m (interquartile range: 16.5-28.2). There was no statistically significant difference in eGFR before the procedure and 30 days after the procedure (P=0.79). No patient required dialysis 30 days after the procedure. Two patients required initiation of dialysis at 1 year after the procedure., Conclusion: In patients with advanced CKD and previous CABG, ULCA may be performed with high procedural success and without complications, minimizing the risk of CIN in these high-risk patients.

While deceased donor renal transplants (DDRT) from donors with either acute kidney injury (AKI) or long cold ischemia time (CIT) are associated with increased risk of delayed graft function (DGF), recipients of these kidneys have good patient and allograft survival. There are limited data on whether kidneys with both AKI and long CIT have outcomes similar to kidneys with only one of these insults. Using data from the Scientific Registry of Transplant Recipients, we analyzed transplant outcomes in patients (2005-2015) receiving kidneys with AKI (terminal creatinine ≥2.0 mg/dl) and CIT 24-30 h (n = 1289), 30-36 h (n = 734), and >36 h (n = 614), using kidneys with AKI and CIT <24 h (n = 5434) as a reference. DGF was more common with increasing CIT up to 36 h, then decreased slightly (41.2% vs. 46.8% vs. 52.5% vs. 50.2%, P < 0.001). Death-censored graft survival (DCGS) at 3 years was better with CIT <24 h compared with other groups (92.5% vs. 90.8% vs. 92% vs. 89.2%, P = 0.018). On multivariable analysis, donor creatinine was predictive of DCGS, whereas only CIT >36 h was predictive of DCGS (aHR 1.27, P = 0.03). Recipients transplanted with kidneys with both AKI and long CIT have excellent intermediate-term outcomes., (© 2019 Steunstichting ESOT.)

Background: Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic kidney disease, which affects more than 1 in 10 persons globally., Methods: We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings., Results: In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients [23.9%]) and nephropathy of unknown origin (48 of 281 patients [17.1%]). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management., Conclusions: Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.).

Background and Objectives: Biopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial., Design, Setting, Participants, & Measurements: We compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists ( n =270). We also examined agreement for sequential procurement biopsies performed on the same kidney ( n =116 kidneys)., Results: For kidneys on which more than one procurement biopsy was performed ( n =116), category agreement was found in only 64% of cases ( κ =0.14). For all kidneys ( n =270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases ( κ =0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement ( κ =0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% ( κ =0.13) and 80% ( κ =0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure., Conclusions: We found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes., (Copyright © 2018 by the American Society of Nephrology.)

The proportion of deceased donor kidneys procured for transplant but subsequently discarded has been growing steadily in the United States, but factors contributing to the rising discard rate remain unclear. To assess the reasons for and probability of organ discard we assembled a cohort of 212,305 deceased donor kidneys recovered for transplant from 2000-2015 in the SRTR registry that included 36,700 kidneys that were discarded. 'Biopsy Findings' (38.2%) was the most commonly reported reason for discard. The median Kidney Donor Risk Index of discarded kidneys was significantly higher than transplanted organs (1.78 vs 1.12), but a large overlap in the quality of discarded and transplanted kidneys was observed. Kidneys of donors who were older, female, Black, obese, diabetic, hypertensive or HCV-positive experienced a significantly increased odds of discard. Kidneys from donors with multiple unfavorable characteristics were more likely to be discarded, whereas unilaterally discarded kidneys had the most desirable donor characteristics and the recipients of their partner kidneys experienced a one-year death-censored graft survival rate over 90%. There was considerable geographic variation in the odds of discard across the United States, which further supports the notion that factors beyond organ quality contributed to kidney discard. Thus, while the discard of a small fraction of organs procured from donors may be inevitable, the discard of potentially transplantable kidneys needs to be avoided. This will require a better understanding of the factors contributing to organ discard in order to remove the disincentives to utilize less-than-ideal organs for transplantation., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The recent evolution in immunosuppression therapy has led to significant improvement in short-term kidney allograft outcomes; however, this progress did not translate into similar improvement in long-term graft survival. The latter, at least in part, is likely to be attributed to immunosuppressant side effects. In this review, we focus on the histologic manifestations of calcineurin inhibitor and mammalian target of rapamycin inhibitor toxicity. We discuss the pathologic features attributed to such toxicity and allude to the lack of highly specific pathognomonic lesions. Finally, we highlight the importance of clinicopathologic correlation to achieve a meaningful pathologic interpretation.

Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation of the impact of weekends on transplantation. Compared with weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval: 1.13-1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval: 1.10-1.17). Weekend discards were of a significantly higher quality than weekday discards (Kidney Donor Profile Index: 76.5% vs. 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI)>85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80-90% and >90%). Kidneys with KDPI>90% were associated with increased odds of discard (OR=1.99, 95% CI 1.74-2.29) compared to ones with KDPI<80%. DKTs of KDPI>90% were associated with lower overall allograft failure (HR=0.74, 95% CI 0.62-0.89) and better patient survival (HR=0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI>90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The number of kidneys obtained from deceased diabetic donors available for transplantation has increased >eightfold increase in the past 15 years. We assessed allograft outcomes associated with deceased diabetic donors and compared them with that of standard and extended criteria donors (ECD) in the UNOS data registry. We identified 1982 recipients of diabetic standard criteria donors over a 10-year period from 1995 through 2004. Both overall and death-censored survival of organs from diabetic standard criteria donors was significantly better than that of organs obtained from nondiabetic ECD while inferior to that from nondiabetic standard criteria donors. Compared with ECD donors, diabetic donors had lower serum creatinine, less cold ischemia and these kidneys were less likely to be pump-perfused. Recipients of diabetic kidneys were younger and less likely to experience delayed graft function compared with recipient of ECD kidneys. More recently, many diabetic donor kidneys have been given to diabetic recipients with early graft survival being similar to that among nondiabetic recipients. These findings demonstrate the potential to expand and to improve utilization of this resource without compromising outcomes for recipients. Improved, evidence-based evaluation and allocation of deceased diabetic donor kidneys is needed to optimize their use., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose of Review: The Model for End-Stage Liver Disease (MELD) scoring system for prioritizing patients for liver transplantation heavily weights serum creatinine, leading to increased numbers of liver transplant patients with renal insufficiency receiving both liver-alone transplants and liver-kidney transplants. With available organs being scarce, review of recent outcomes and guidelines for their use is timely., Recent Findings: Despite lower average renal function in liver transplant recipients in the era of Model for End-Stage Liver Disease scoring, and poor renal function predicting inferior outcomes, overall outcomes are unchanged. Combined liver-kidney transplants have increased three-fold. Despite inferior short-term kidney and liver-graft survival rates, long-term success rates are equivalent to single-organ transplantation. Only patients requiring dialysis at the time of transplantation clearly benefit from combined liver-kidney transplants. Waitlisted patients with nonresolving severe acute kidney injury for 6-8 weeks or substantial irreversible renal parenchymal damage are also deemed appropriate candidates. Many combined liver-kidney recipients have lesser degrees of renal dysfunction, however. Accurate determination of renal function in patients with cirrhosis remains problematic., Summary: Appropriate patients with irreversible end-stage renal and liver disease clearly deserve combined liver-kidney transplants. More data on the reliable assessment of renal function, renal pathology, and outcomes are needed, however.

We report the clinical and pathologic findings in 7 patients with systemic lupus erythematosus and minimal change disease. All 7 patients presented with full nephrotic syndrome including peripheral edema, nephrotic range proteinuria (mean 9.6 g/day), and hypoalbuminemia (mean 1.8 g/dl). In all cases, renal biopsy revealed diffuse foot process effacement in the absence of significant peripheral capillary wall immune deposits, findings consistent with minimal-change disease. In addition, 5 cases displayed mesangial electron-dense deposits, with or without associated mesangial proliferation, consistent with underlying lupus nephritis class II. In all cases, steroid therapy induced a rapid remission of nephrotic syndrome. Minimal change disease is an underrecognized and readily reversible form of nephrotic syndrome in systemic lupus erythematosus. Because it may occur superimposed on mild mesangial proliferative lupus nephritis, this entity may be misinterpreted as an atypical presentation of lupus nephritis class II. Proper recognition of this entity requires careful integration of the renal biopsy immunofluorescence and electron microscopic findings.

Objective: To find out the association between social class and coronary risk factors in women., Design and Setting: Cross-sectional surveys were conducted in six-twelve urban streets in each of five cities from various regions of India following a common study protocol and criteria of diagnosis., Subjects and Methods: We randomly selected 3257 women, aged 25-64 years inclusive, from the cities of Moradabad (n=902), Trivandrum (n=760) Calcutta (n=410), Nagpur (n=405) and Bombay (n=780). Evaluation was by questionnaires validated at Moradabad. All subjects, after pooling of data, were divided into social class 1 (n=985), social class 2 (n=790), social class 3 (n=674), social class 4 (n=602) and social class 5 (n=206), based on various attributes of socioeconomic status., Results: The prevalence of hypertension, diabetes mellitus, family history of coronary disease, obesity, central obesity and sedentary lifestyle were significantly associated with higher social classes and tobacco consumption was not associated with social class. Oral contraceptive intake and postmenopausal status were also more common among higher social classes, which may be due to more education and a longer lifespan among the higher social classes, respectively. Mean total cholesterol, high density lipoprotein cholesterol, systolic and diastolic blood pressure, mean body mass index and waist-hip ratio showed significant association with higher social classes. Mean age, body weight, body mass index, waist-hip ratio, systolic and diastolic blood pressure, total cholesterol and 2-h blood glucose were significantly positively correlated with social class, as assessed by Spearman's rank correlation. Higher social classes 1-3 were more common in Trivandrum and Bombay than in Moradabad. The prevalence of hypertension, diabetes mellitus and being overweight (body mass index >25 kg/m2) were also more common in Trivandrum and Bombay compared to Moradabad. Undernutrition was negatively associated with higher social classes and was more common in Moradabad and Nagpur than Trivandrum., Conclusions: Higher social classes among Indian urban women have a higher prevalence of coronary risk factors, hypertension, diabetes mellitus, being overweight, central obesity, sedentary lifestyle, family history of coronary disease, oral contraceptive intake and postmenopausal status. Mean concentrations of total and high density lipoprotein cholesterol were also significantly associated with higher social classes.

Objective: To study the prevalence of central obesity and age-specific waist:hip ratio of urban women from five Indian cities., Design and Setting: Cross-sectional surveys were conducted in 6-12 urban streets in different parts of India using similar methods of sample selection and criteria of diagnosis., Subjects and Methods: We randomly selected 3212 women, aged 25-64 years, from Moradabad (n = 902), Trivandrum (n = 760), Calcutta (n = 365), Nagpur (n = 405), and Bombay (n = 780). Evaluation was by a questionnaire administered by a physician and a dietician, a physical examination, and anthropometric measurements., Results: The overall prevalence of central obesity among the total number of women was 55.0%, with the highest prevalence in Calcutta (62.2%) and the lowest in Bombay (47.4%). Waist:hip ratio was 0.85 +/- 0.13 (mean +/- SD) with the highest ratio for women in Calcutta (0.87 +/- 0.12) and the lowest for women in Moradabad (0.84 +/- 0.16). After pooling of data from all five cities, multivariate logistic regression analysis showed that, regardless of age, body mass index (> 23 kg/m2; odds ratio 1.12), sedentary lifestyle (odds ratio 2.51), and family history of obesity (odds ratio 2.15) were strongly associated with central obesity. Excess intake of fat was weakly associated with central obesity but age was not a risk factor for central obesity, although the prevalence was highest among those aged over 55 years in Moradabad, Calcutta, and Nagpur., Conclusions: The overall prevalence of central obesity among the urban women of India has increased, more so in Calcutta and Trivandrum. Body mass index, sedentary lifestyle, and family history of excess intake of fat were significant risk factors for central obesity.

These cross-sectional surveys included 1769 rural (894 men and 875 women) and 1806 urban (904 men and 902 women) randomly selected subjects between 25-64 years of age from Moradabad in North India. The total prevalence of coronary artery disease based on clinical history and electrocardiogram was significantly higher in urban compared to rural men (11.0 vs. 3.9%) and women (6.9 vs. 2.6%), respectively. Food consumption patterns showed that important differences in relation to coronary artery disease were higher intake of total visible fat, milk and milk products, meat, eggs, sugar and jaggery in urban compared to rural subjects. Prevalence of coronary artery disease in relation to visible fat intake showed a higher prevalence rate with higher visible fat intake in both sexes and the trend was significant for total prevalence rates both for rural and urban men and women. Subgroup analysis among urban (694 men and 694 women) and rural (442 men and 435 women) subjects consuming moderate to high fat diets showed that subjects eating trans fatty acids plus clarified butter or those consuming clarified butter as total visible fat had a significantly higher prevalence of coronary artery disease compared to those consuming clarified butter plus vegetable oils in both rural (9.8, 7.1 vs. 3.0%) and urban (16.2, 13.5 vs. 11.0%) men as well as in rural (9.2, 4.5 vs. 1.5%) and urban (10.7, 8.8 vs. 6.4%) women. Univariate and multivariate regression analysis with adjustment for age showed that sedentariness in women, body mass index in urban men and women, milk and clarified butter plus trans fatty acids in both rural and urban in both sexes were significantly associated with coronary artery disease. It is possible that lower intake of total visible fat (20 g/day), decreased intake of milk, increased physical activity and cessation of smoking may benefit some populations in the prevention of coronary artery disease.