Utilizing kidneys from a donor with bile-cast nephropathy.

Here we discuss the successful utilization of a pair of deceased donor kidneys with bile-cast nephropathy. The donor had a kidney donor profile index of 48% and an acute kidney injury requiring continuous renal replacement therapy. Peak donor bilirubin was 40.5 mg/dL, and renal wedge biopsies showed bile-cast nephropathy. Both recipients had delayed graft function lasting up to 4 weeks. The 4-month biopsies showed mild interstitial fibrosis, tubular atrophy, and a resolution of bile casts. These kidney allografts showed the reversible course of cholemic nephropathy and the potential for increasing the utilization of previously discarded kidneys.

Ex-situ machine perfusion in clinical liver transplantation: Current practices and future directions.

Ex-situ machine perfusion of the liver has surmounted traditional limitations associated with static cold storage in the context of organ preservation. This innovative technology has changed the landscape of liver transplantation by mitigating ischemia perfusion injury, offering a platform for continuous assessment of organ quality, and providing an avenue for optimizing use of traditionally marginal allografts. This review summarizes the contemporary clinical applications of machine perfusion devices, and discusses potential future strategies for real-time viability assessment, therapeutic interventions, and modulation of organ function after recovery.

Understanding Delayed Graft Function to Improve Organ Utilization and Patient Outcomes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda.

Liver transplant outcomes using late allocation grafts.

Post-cross clamp late allocation (LA) liver allografts are at increased risk for discard for many reasons including logistical complexity. Nearest neighbor propensity score matching was used to match 2 standard allocation (SA) offers to every 1 LA liver offer performed at our center between 2015 and 2021. Propensity scores were based on a logistic regression model including recipient age, recipient sex, graft type (donation after circulatory death vs. donation after brain death), Model for End-stage Liver Disease (MELD), and DRI score. During this time, 101 liver transplants (LT) were performed at our center using LA offers. In comparing LA and SA offers, there were no differences in recipient characteristics including indication for transplant ( p = 0.29), presence of PVT ( p = 0.19), TIPS ( p = 0.83), and HCC status ( p = 0.24). LA grafts came from younger donors (mean age 43.6 vs. 48.9 y, p = 0.009) and were more likely to come from regional or national Organ Procurement Organizations (OPOs) ( p < 0.001). Cold ischemia time was longer for LA grafts (median 8.5 vs 6.3 h, p < 0.001). Following LT, there were no differences between the 2 groups in intensive care unit ( p = 0.22) and hospital ( p = 0.49) lengths of stay, need for endoscopic interventions ( p = 0.55), or biliary strictures ( p = 0.21). Patient (HR 1.0, 95% CI, 0.47-2.15, p = 0.99) and graft (HR 1.23, 95% CI, 0.43-3.50, p = 0.70) survival did not vary between the LA and SA cohorts. One-year LA and SA patient survival was 95.1% and 95.0%; 1-year graft survival was 93.1% and 92.1%, respectively. Despite the additional logistical complexity and longer cold ischemia time, LT outcomes utilizing LA grafts are similar to those allocated by means of SA. Improving allocation policies specific to LA offers, as well as the sharing of best practices between transplant centers and OPOs, are opportunities to further help minimize unnecessary discards.

Expanding Liver Transplant Opportunities in Older Patients With Nonconventional Grafts.

INTRODUCTION: Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. METHODS: 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. RESULTS: In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. CONCLUSIONS: Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients.

Current opinions on DGF management practices: A survey of the United States and Canada.

INTRODUCTION: Significant center-to-center variation in attitudes and management of delayed graft function (DGF) remains common. METHODS: A survey to describe current DGF practices was developed by workgroup members sponsored by the National Kidney Foundation (NKF) and was distributed to both the NKF DGF workgroup members, kidney transplant program directors and the transplant community within the United States and Canada. Seventy-one percent of NKF workgroup members completed the survey along with 70 unique the United States and three Canadian kidney transplant programs. All Organ Procurement and Transplantation Network (OPTN) regions were represented. RESULTS: DGF was reported to occur at rate of 20%-40% for most centers with 3.9% indicating their incidence to be >60%. Most centers reported longer hospital lengths of stay and more frequent outpatient visits. Despite the commonality of DGF, only half of centers reported having an established protocol to manage DGF. Kidney allograft biopsies were the only consistent DGF management strategy observed, although use of machine perfusion was also heavily favored. Other DGF management strategies voiced by a minority included having established outpatient practices to care for DGF patients and administering outpatient community-based hemodialysis. CONCLUSION: Although approximately a third of survey responders indicated that risk of DGF played a role in their willingness to accept organs, most did not feel that increased cost or clinical impact on outcomes was a deterrent. Future strategies, including broader sharing of best practices, redefining terminology specific to DGF, the establishment of DGF dialysis guidelines and improving access to machine perfusion across OPOs may help reduce discard and improve utilization of kidneys at risk for DGF.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Outcomes with transplanting kidneys offered through expedited allocation.

INTRODUCTION: Expedited out-of-sequence deceased donor kidney allocation is a strategy to avoid discards after early placement attempts have been unsuccessful. Our study aimed to assess outcomes and characteristics of these transplanted kidneys. METHODS: KDPI matching was performed between expedited allocation (EA) and standard allocation (SA) deceased donor kidney transplants performed at our center. RESULTS: Between 2018 and 2021, there were 225 EA offers, and 189 (84%) were transplanted. EA recipients were older (p = .007) and had shorter dialysis vintage (p < .0001). EA kidneys were likely to be nationally allocated (p < .001), have AKI (p < .0001) and longer CIT (p < .0001). There were no differences in EA and SA time-zero kidney biopsies (ci, p = .07; ct, p = .89; cv, p = .95; ah, p = .79). EA kidneys had more DGF (p = .0006), but there were no differences in DGF duration (p = .83), hospital length of stay (p = .43), 1- and 2-year eGFR (p = .16, p = .99), patient (p = .34), or death-censored graft (p = .66) survival. CONCLUSION: During this study period, our center transplanted 189 kidneys through EA following local-regional declines. These kidneys often came from AKI donors and had more DGF but had similar outcomes to KDPI-matched SA kidneys. Although it has been suggested that EA has the potential to worsen transplant disparities, transplant center level decisions on organ acceptance contribute to these variations.

Outcomes and Health Care Utilization After Early Hospital Dismissal in Kidney Transplantation: An Analysis of 1001 Consecutive Cases.

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.

Donation after circulatory death transplant outcomes using livers recovered by local surgeons.

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.

Outcomes of dual kidney transplants from high KDPI kidneys are superior compared to single kidney high KDPI transplants at 1 year.

Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P = .02) and donors had a higher KDPI score (median 96% vs. 91%, P < .0001). DKT operative time was higher compared to SKT (+1.4 hours, P < .0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P = .77) and hospital length of stay (median 4.0 vs. 3.0 days, P = .21) between DKT and SKT. Grade I Clavien-Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P = .008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P = .04), interstitial fibrosis (P = .02), tubular atrophy (P = .01), and arterial thickening (P = .03) on 1-year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1- (P = .004) and 2-years post-transplant (P = .01). There were no differences in patient (HR 1.3, 95% CI .5-3.3, P = .58) or graft (HR 1.1, 95% CI .5-2.3, P = .83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard.

Kidney donor profile index and post-transplant health care utilization: Implications for value of transplant care delivery.

BACKGROUND: Centers 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. METHODS: We 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. RESULTS: High (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). CONCLUSIONS: High and low KDPI KTRs demonstrated similar 90-day risk-adjusted health care utilization, which should encourage use of high KDPI kidneys.

Association of DGF and Early Readmissions on Outcomes Following Kidney Transplantation.

Concerns regarding outcomes and early resource utilization are potential deterrents to broader use of kidneys at risk for delayed graft function (DGF). We assessed outcomes specific to kidneys with DGF that required early readmission following transplant. Three groups were identified: 1) recipients with DGF not requiring readmission, 2) recipients with DGF having an isolated readmission, and 3) recipients with DGF requiring ≥2 readmissions. Most recipients either required a single readmission (26.8%, n = 247) or no readmission (56.1%, n = 517); 17.1% (n = 158), had ≥2 readmissions. Recipients requiring ≥2 readmissions were likely to be diabetic (53.8%, p = 0.04) and have longer dialysis vintage (p = 0.01). Duration of DGF was longer with increasing number of readmissions (p < 0.001). There were no differences in patient survival for those with DGF and 0, 1 and ≥2 readmissions (p = 0.13). Graft survival, however, was lower for those with ≥2 readmissions (p < 0.0001). This remained true when accounting for death-censored graft loss (p = 0.0012). Additional subgroup analysis was performed on mate kidneys with and without DGF and mate kidneys, both with DGF, with and without readmissions. For these subgroups, there were no differences in patient or graft survival. As a whole, patients with DGF have excellent outcomes, however, patients with DGF requiring ≥2 readmissions have lower graft survival. A better understanding of recipient variables contributing to multiple readmissions may allow for improvements in the utilization of DGF at-risk kidneys.

Duration of delayed graft function and its impact on graft outcomes in deceased donor kidney transplantation.

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. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. RESULTS: 1714 DDKT recipients 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 number ID: 20-011561.

Decreasing Significance of Early Allograft Dysfunction with Rising Use of Nonconventional Donors.

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7−1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7−1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients.

BACKGROUND & AIMS: Grafts from HCV-seropositive donors can now be considered for liver transplantation (LT) owing to the advent of direct-acting antivirals (DAAs). We report on our multicenter experience of transplanting liver grafts from HCV-seropositive donors into HCV-seronegative recipients. METHODS: This is a prospective multicenter observational study evaluating outcomes in adult HCV-seronegative LT recipients who received grafts from HCV-seropositive donors in 3 US centers. RESULTS: From 01/18 to 09/19, 34 HCV-seronegative LT recipients received grafts from HCV-seropositive donors (20 HCV-viremic and 14 non-viremic). Seven grafts were from cardiac-dead donors. The median MELD-Na score at allocation was 20. Six recipients underwent simultaneous liver-kidney transplant and 4 repeat LT. No recipient of an HCV-non-viremic graft developed HCV viremia. All 20 patients who received HCV-viremic grafts had HCV viremia confirmed within 3 days after LT. DAA treatment was started at a median of 27.5 days after LT. Median pre-treatment viral load was 723,000 IU/ml. All (20/20) patients completed treatment and achieved SVR12. Treatment was well tolerated with minimal adverse events. One patient developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease, despite achieving viral clearance. This patient died due to presumed infectious complications. A recipient of an HCV-non-viremic graft died with acute myocardial infarction 610 days post LT. CONCLUSIONS: Transplantation of liver grafts from HCV-seropositive donors into HCV-seronegative recipients resulted in excellent short-term outcomes. Antiviral therapy was effective and well tolerated. Careful ongoing assessment and prompt initiation of antiviral therapy are recommended. Longer term follow-up in carefully conducted clinical trials is still required to confirm these results. LAY SUMMARY: This study shows that livers from donors exposed to HCV expand the donor pool and can be used safely in patients who are seronegative for hepatitis C infection. Treatment, initiated early post transplantation, is effective and resulted in cure in all patients.

Successful outcomes with transplanting kidneys from deceased donors with acute kidney injuryon temporary renal replacement therapy.

BACKGROUND AND OBJECTIVES: We aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT). MATERIALS AND METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Transplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.

Transplant outcomes using kidneys from high KDPI acute kidney injury donors.

Kidney 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.

Early technical pancreas failure in Simultaneous Pancreas-Kidney Recipients does not impact renal allograft outcomes.

Early 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.

Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.

Histologic 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.