Reddy, Kunam S.

Abstract Donation after circulatory death (DCD) liver transplantation (LT) outcomes have been attributed to multiple variables, including procurement surgeon recovery techniques. Outcomes of 196 DCD LTs at Mayo Clinic Arizona were analyzed based on graft recovery by a surgeon from our center (transplant procurement team [TPT]) versus a local procurement surgeon (non‐TPT [NTPT]). A standard recovery technique was used for all TPT livers. The recovery technique used by the NTPT was left to the discretion of that surgeon. A total of 129 (65.8%) grafts were recovered by our TPT, 67 (34.2%) by the NTPT. Recipient age (p = 0.43), Model for End‐Stage Liver Disease score (median 17 vs. 18; p = 0.22), and donor warm ischemia time (median 21.0 vs. 21.5; p = 0.86) were similar between the TPT and NTPT groups. NTPT livers had longer cold ischemia times (6.5 vs. 5.0 median hours; p < 0.001). Early allograft dysfunction (80.6% vs. 76.1%; p = 0.42) and primary nonfunction (0.8% vs. 0.0%; p = 0.47) were similar. Ischemic cholangiopathy (IC) treated with endoscopy occurred in 18.6% and 11.9% of TPT and NTPT grafts (p = 0.23). At last follow‐up, approximately half of those requiring endoscopy were undergoing a stent‐free trial (58.3% TPT; 50.0% NTPT; p = 0.68). IC requiring re‐LT in the first year occurred in 0.8% (n = 1) of TPT and 3.0% (n = 2) of NTPT grafts (p = 0.23). There were no differences in patient (hazard ratio [HR], 1.95; 95% confidence interval [CI], 0.76–5.03; p = 0.23) or graft (HR, 1.99; 95% CI, 0.98–4.09; p = 0.10) survival rates. Graft survival at 1 year was 91.5% for TPT grafts and 95.5% for NTPT grafts. Excellent outcomes can be achieved using NTPT for the recovery of DCD livers. There may be an opportunity to expand the use of DCD livers in the United States by increasing the use of NTPT.

AbstractBackgroundCenters discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization.MethodsWe conducted a retrospective cohort study from a high‐volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long‐term graft function and patient survival.ResultsHigh (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P = .66), and readmission rates at 7, 30, and 90 days after surgery (all, P > .05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P > .05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P < .001), but similar 3‐year patient and graft survival (both, P > .09).ConclusionsHigh and low KDPI KTRs demonstrated similar 90‐day risk‐adjusted health care utilization, which should encourage use of high KDPI kidneys.

Abstract Background. There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function.Methods. We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020 with DGF to determine factors associated with DGF duration as well as the impact of DGF duration on 1) acute rejection, BKV infection, progression of fibrosis on protocol biopsy, and death censored graft survival 2) resource utilization, including hospital length of stay and readmissions. DGF duration was assessed at three 14-day intervals: <14 DGF days, 14-27 DGF days, >28 DGF days.Results. There were 1714 DDKT were included, 59.4% (n=1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted >28 days. Conclusions. Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting <28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. Trial Registration. Retrospective study approved by Mayo Clinic IRB.

AbstractHistologic findings on 1‐year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1‐year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1‐year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1‐year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10‐fold cross‐validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c‐statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c‐statistic. Importantly, the majority of patients with graft loss in the prospective study had 1‐year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1‐year biopsy and eGFR > 40) remains difficult.

AbstractBackground and objectivesWe aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT).Materials and methodsA total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney.ResultsThe study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3‐RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0,P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups,P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI.ConclusionsTransplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.

AbstractKidney transplant (KT) outcomes from high kidney donor profile index (KDPI ≥85%) donors with acute kidney injury (AKI) remain underreported. KT from 172 high KDPI Acute Kidney Injury Network (AKIN) stage 0‐1 donors and 76 high KDPI AKIN stage 2‐3 donors from a single center were retrospectively assessed. The AKIN 2‐3 cohort had more delayed graft function (71% vs. 37%, p < .001). At one year, there were no differences in the estimated glomerular filtration rate (44 ± 17 vs. 46 ± 18, p = .42) or fibrosis on protocol biopsy (ci, p = .85). Donor terminal creatinine (p = .59) and length of delayed graft function (p = .39) did not impact one‐year eGFR. There were more primary nonfunction (PNF) events in the high KDPI AKIN 2‐3 group (5.3% vs. 0.6%, p = .02). With a median follow‐up of 3.8 years, one‐year death‐censored graft failure was 3.5% for AKIN 0‐1 and 14.5% for AKIN 2‐3 (HR 2.40, 95% CI 1.24‐4.63, p = .01). Although AKIN stage 2‐3 high KDPI kidneys had comparable one‐year eGFR to AKIN stage 0‐1 high KDPI kidneys, there were more PNF occurrences and one‐year death‐censored graft survival was reduced. Given these findings, additional precautions should be undertaken when assessing and utilizing kidneys from severe AKI high KDPI donors.

AbstractEarly pancreas loss in simultaneous pancreas–kidney (SPK) transplants has been associated with longer perioperative recovery and reduced kidney allograft function. We assessed the impact of early pancreas allograft failure on transplant outcomes in a contemporary cohort of SPK patients (n = 218). Early pancreas allograft loss occurred in 12.8% (n = 28) of recipients. Delayed graft function (DGF) was more common (21.4% vs. 7.4%, p = 0.03) in the early pancreas loss group, but there were no differences in hospital length of stay (median 6.5 vs. 7.0, p = 0.22), surgical wound complications (p = 0.12), or rejection episodes occurring in the first year (p = 0.87). Despite differences in DGF, both groups had excellent renal function at 1 year post‐transplant (eGFR 64.1 ± 20.8 vs. 65.8 ± 22.9, p = 0.75). There were no differences in patient (HR 0.58, 95% CI 0.18–1.87, p = 0.26) or kidney allograft survival (HR 0.84, 95% CI 0.23–3.06, p = 0.77). One‐ and 2‐year protocol kidney biopsies were comparable between the groups and showed minimal chronic changes; the early pancreas loss group showed more cv changes at 2 years (p = 0.04). Current data demonstrate good outcomes and excellent kidney allograft function following early pancreas loss.

Objective: To understand whether reduced lengths of stay after kidney transplantation were associated with excess health care utilization in the first 90 days or long-term graft and patient survival outcomes. Background: Reducing length of stay after kidney transplant has an unknown effect on post-transplant health care utilization. We studied this association in a cohort of 1001 consecutive kidney transplants. Methods: We retrospectively reviewed 2011–2015 data from a prospectively-maintained kidney transplant database from a single center. Results: A total of 1001 patients underwent kidney transplant, and were dismissed from the hospital in 3 groups: Early [≤2 days] (19.8%), Normal [3–7 days] (79.4%) and Late [>7 days] (3.8%). 34.8% of patients had living donor transplants (Early 51%, Normal 31.4%, Late 18.4%, P < 0.001). Early patients had lower delayed graft function rates (Early 19.2%, Normal 32%, Late73.7%, P = 0.001). By the hospital dismissal group, there were no differences in readmissions or emergency room visits at 30 or 90 days. Glomerular filtration rate at 12 months and rates of biopsy-proven acute rejection were also similar between groups. The timing of hospital dismissal was not associated with the risk-adjusted likelihood of readmission. Early and Normal patients had similar graft and patient survival. Late dismissal patients, who had higher rates of cardiovascular complications, had significantly higher late mortality versus Normal dismissal patients in unadjusted and risk-adjusted models. Conclusion: Dismissing patients from the hospital 2 days after kidney transplant is safe, feasible, and improves value. It is not associated with excess health care utilization or worse short or long-term transplant outcomes.

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described. Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients. Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08–10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23–13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1–34.6, p = 0.04). Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

Background The use of procurement biopsies for assessing kidney quality has been implicated as a driver of the nearly 20% kidney discard rate in the United States. Yet in some contexts, biopsies may boost clinical confidence, enabling acceptance of kidneys that would otherwise be discarded. We leveraged a novel organ offer simulation platform to conduct a controlled experiment isolating biopsy effects on offer acceptance decisions. Methods Between November 26 and December 14, 2018, 41 kidney transplant surgeons and 27 transplant nephrologists each received the same 20 hypothetical kidney offers using a crossover design with weekend “washout” periods. Mini-study 1 included four, low serum creatinine (<1.5 mg/dl) donor offers with arguably “poor” biopsy findings that were based on real offers that were accepted with successful 3-year recipient outcome. For each of the four offers, two experimental variants—no biopsy and “good” biopsy—were also sent. Mini-study 2 included four AKI offers with no biopsy, each having an offer variant with “good” biopsy findings. Results Among low serum creatinine donor offers, we found approximately threefold higher odds of acceptance when arguably poor biopsy findings were hidden or replaced with good biopsy findings. Among AKI donor offers, we found nearly fourfold higher odds of acceptance with good biopsy findings compared with no biopsy. Biopsy information had profound but variable effects on decision making: more participants appeared to have been influenced by biopsies to rule out, versus rule in, transplantable kidneys. Conclusions The current use of biopsies in the United States appears skewed toward inducing kidney discard. Several areas for improvement, including reducing variation in offer acceptance decisions and more accurate interpretation of findings, have the potential to make better use of scarce, donated organs. Offer simulation studies are a viable research tool for understanding decision making and identifying ways to improve the transplant system.