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Introduction: The study purpose was to review retrospectively our single‐center experience transplanting kidneys from deceased donors (DD) with acute kidney injury (AKI) according to terminal serum creatinine (tSCr) level. Methods: AKI kidneys were defined by a doubling of the DD's admission SCr and a tSCr ≥ 2.0 mg/dL. Results: From 1/07 to 11/21, we transplanted 236 AKI DD kidneys, including 100 with a tSCr ≥ 3.0 mg/dL (high SCr AKI group, mean tSCr 4.2 mg/dL), and the remaining 136 from DDs with a tSCr of 2.0–2.99 mg/dL (lower SCr AKI group, mean tSCr 2.4 mg/dL). These two AKI groups were compared to 996 concurrent control patients receiving DD kidneys with a tSCr < 1.0 mg/dL. Mean follow‐up was 69 months. Delayed graft function (DGF) rates were 51% versus 46% versus 29% (p < 0.0001), and 5‐year patient and death‐censored kidney graft survival rates were 96.8% versus 83.5% versus 82.2% (p = 0.002) and 86.7% versus 77.8% versus 78.8% (p = 0.18) in the high tSCr AKI versus lower tSCr AKI versus control groups, respectively. Conclusions: Despite a higher incidence of DGF, patients receiving kidneys from DDs with tSCr levels ≥3.0 mg/dL have acceptable medium‐term outcomes compared to either AKI DDs with a lower tSCr or DDs with a tSCr < 1.0 mg/dL. [ABSTRACT FROM AUTHOR]

Introduction: There is limited experience transplanting kidneys from either expanded criteria donors (ECD) or donation after circulatory death (DCD) deceased donors with terminal acute kidney injury (AKI). Methods: AKI kidneys were defined by a donor terminal serum creatinine level >2.0 mg/dL whereas non‐ideal deceased donor (NIDD) kidneys were defined as AKI/DCD or AKI/ECDs. Results: From February 2007 to March 2023, we transplanted 266 single AKI donor kidneys including 29 from ECDs, 29 from DCDs (n = 58 NIDDs), and 208 from brain‐dead standard criteria donors (SCDs). Mean donor age (43.7 NIDD vs. 33.5 years SCD), KDPI (66% NIDD vs. 45% SCD), and recipient age (57 NIDD vs. 51 years SCD) were higher in the NIDD group (all p <.01). Mean waiting times (17.8 NIDD vs. 24.2 months SCD) and dialysis duration (34 NIDD vs. 47 months SCD) were shorter in the NIDD group (p <.05). Delayed graft function (DGF, 48%) and 1‐year graft survival (92.7% NIDD vs. 95.9% SCD) was similar in both groups. Five‐year patient and kidney graft survival rates were 82.1% versus 89.9% and 82.1% versus 75.2% (both p = NS) in the NIDD versus SCD groups, respectively. Conclusions: The use of kidneys from AKI donors can be safely liberalized to include selected ECD and DCD donors. [ABSTRACT FROM AUTHOR]

Introduction: Many kidney transplant (KT) centers decline patients with a body mass index (BMI) ≥40 kg/m2. This study's aim was to evaluate KT outcomes according to recipient BMI. Methods: We performed a single‐center, retrospective review of adult KTs comparing BMI ≥40 patients (n = 84, BMI = 42 ± 2 kg/m2) to a matched BMI < 40 cohort (n = 84, BMI = 28 ± 5 kg/m2). Patients were matched for age, gender, race, diabetes, and donor type. Results: BMI ≥40 patients were on dialysis longer (5.2 ± 3.2 years vs. 4.1 ± 3.5 years, p =.03) and received lower kidney donor profile index (KDPI) kidneys (40 ± 25% vs. 53 ± 26%, p =.003). There were no significant differences in prevalence of delayed graft function, reoperations, readmissions, wound complications, patient survival, or renal function at 1 year. Long‐term graft survival was higher for BMI ≥40 patients, including after adjusting for KDPI (BMI ≥40: aHR = 1.79, 95% CI = 1.09–2.9). BMI ≥40 patients had similar BMI change in the first year post‐transplant (delta BMI: BMI ≥ 40 +.9 ± 3.3 vs. BMI < 40 +1.1 ± 3.2, p =.59). Conclusions: Overall outcomes after KT were comparable in BMI ≥40 patients compared to a matched cohort with lower BMI with improved long‐term graft survival in obese patients. BMI‐based exclusion criteria for KT should be reexamined in favor of a more individualized approach. [ABSTRACT FROM AUTHOR]

Aim: The influence of dialysis modality and duration on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) remains uncertain. Methods: We performed a single‐center retrospective review in 255 SPKT recipients according to dialysis modality (55 preemptive/no dialysis‐ND, 70 peritoneal dialysis–PD, 130 hemodialysis–HD) and duration (55 none, 137 < 2 years, 41 2‐4 years, 22 > 4 years). Results: Mean follow‐up was 9.4 years (median 9.2 years). Early (3‐month) relaparotomy rate (20% ND vs. 36% PD/HD, p =.03) was lower in ND patients. There were no differences in early graft loss, patient survival, overall or death‐censored kidney or pancreas graft survival rates (GSR) at 1 or 10 years follow‐up. When analyzing dialysis duration, there were no differences in rates of pancreas thrombosis or early pancreas graft loss. Kidney delayed graft function (DGF) was lower in the ND/short dialysis groups combined (1.0%), compared to the intermediate/long dialysis groups combined (9.5%, p =.003). Early relaparotomy rates were higher with longer duration of dialysis (p =.045 between ND and >4 years of dialysis). Patient survival in the long dialysis group was 50% compared to 69.5% in the other three groups combined (p =.09). However, both overall and death‐censored kidney and pancreas GSR were comparable. Conclusions: Preemptively transplanted patients had a lower incidence of kidney DGF and relaparotomy whereas patient survival was slightly lower with longer dialysis vintage prior to SPKT. Dialysis modality and duration did not influence either overall or death‐censored pancreas or kidney GSR in patients with short waiting times, low KDPI donor organs, and dialysis duration up to 4 years. [ABSTRACT FROM AUTHOR]

Dramatic improvements have been seen in shortterm kidney allograft survival over recent decades with introduction of more potent immunosuppressant medications and regimens. Unfortunately, improvements in long-term graft survival have lagged behind. The genomics revolution is providing new insights regarding the potential impact of kidney donor genotypes on long-term graft survival. Variation in the donor apolipoprotein L1 (APOL1), caveolin 1 (CAV1), and multi-drug resistance 1 encoding P-glycoprotein genes (ABCB1)are all associated with graft survival after kidney transplantation. Although the precise mechanisms whereby these donor gene variants confer risk for graft loss have yet to be determined, these findings provide novel opportunities for modifying interactive environmental factors and optimizing kidney allocation with the ultimate goal of improving long-term graft survival rates. Keywords ABCB1 . APOL1 . CAV1 Genetics Kidney disease . Transplantation, Introduction End-stage kidney disease (ESKD) remains a major public health concern with increasing numbers of prevalent patients on dialysis and recent annual Medicare costs exceeding $29 billion. Kidney transplantation is [...]

Introduction: Long‐term outcomes of kidney transplantation from deceased donors (DDKTs) with terminal acute kidney injury (AKI) are not well defined. Methods: Single center retrospective review of DDKTs from 1/31/07‐12/31/19. AKI kidneys were defined by a doubling of the donor's admission serum creatinine (SCr) level AND a terminal SCr ≥2.0 mg/dl. Results: A total of 188 AKI DDKTs were performed, including 154 from brain‐dead standard criteria donors (SCD). Mean donor age was 36 years and mean Kidney Donor Profile Index was 50%; mean admission and terminal SCr levels were 1.3 and 3.1 mg/dl, respectively. With a mean follow‐up of 94 months (median 89 months), overall patient (both 71.3%) and graft survival (54% AKI vs. 57% non‐AKI) rates were comparable to concurrent DDKTs from brain‐dead non‐AKI SCDs (n = 769). Delayed graft function (DGF) was higher in AKI kidney recipients (47% vs. 20% non‐AKI DDKTs, p <.0001). DGF was associated with lower graft survival in recipients of both AKI and non‐AKI SCD kidneys but the impact was earlier and more pronounced in non‐AKI recipients. Conclusions: Despite having more than twice the incidence of DGF, kidneys from deceased donors with terminal AKI have long‐term outcomes comparable to non‐AKI SCD kidneys and represent a safe and effective method to expand the donor pool. [ABSTRACT FROM AUTHOR]

Introduction: The influence of sex on outcomes following simultaneous pancreas–kidney transplantation (SPKT) in the modern era is uncertain. Methods: We retrospectively studied 255 patients undergoing SPKT from 11/2001 to 8/2020. Cases were stratified according to donor (D) sex, recipient (R) sex, 4 D/R sex categories, and D/R sex‐matched versus mismatched. Results: D‐male was associated with slightly higher patient (p =.08) and kidney (p =.002) but not pancreas (p =.23) graft survival rates (GSR) compared to D‐female. There were no differences in recipient outcomes other than slightly higher pancreas thrombosis (8% R‐female vs. 4.2% R‐male, p =.28) and early relaparotomy rates in female recipients (38% R‐female vs. 29% R‐male, p =.14). When analyzing the 4 D/R sex categories, the two D‐male groups had higher kidney GSRs compared to the two D‐female groups (p =.01) whereas early relaparotomy and pancreas thrombosis rates were numerically higher in the D‐female/R‐female group compared to the other three groups. Finally, there were no significant differences in outcomes between sex‐matched and sex‐mismatched groups although overall survival outcomes were lower with female donors irrespective of recipient sex. Conclusions: The influence of D/R sex following SPKT is subject to multiple confounding issues but survival rates appear to be higher in D‐male/R‐male and lower in D‐female/R‐male categories. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to analyze the combined effect of cold ischemia time (CIT) and donation after cardiac death (DCD, with requisite warm ischemia time, WIT) on kidney transplant (KT) outcomes. Methods: Single center retrospective review of DCD KT recipients stratified by CIT. Results: From 6/08 to 10/20, we performed 446 DCD KTs (115 CIT ≤20, 205 CIT 20–30, 88 CIT 30–40, 38 CIT ≥40 h). Mean WITs (26/25/27/23 min) and KDPI values (59%/55%/55%/59%) were similar while mean CITs (16.4/23.6/33.4/42.5 h) and pump times (10.3/13.6/16.1/20.4 h) differed across groups (P <.05). With a mean 6‐year follow‐up, patient survival (84%/84%/74%/84%) was similar. Kidney graft survival (GS) (72%/72%/56%/58%) and death censored GS (DCGS) (82%/80%/63%/67%) rates decreased whereas rates of primary nonfunction (PNF,.9%/2.4%/9.1%/7.9%) and delayed graft function (DGF) (36%/48%/50%/69%) increased with longer CIT (≥30 h, P <.05). Meaningful years free of dialysis, which we refer to as Allograft Life Years, were achieved in all cohorts (4.5/4.3/3.9/4.3 years per patient transplanted). Conclusion: DCD donor kidneys with prolonged CIT (≥30 h) are associated with increased rates of DGF and PNF, along with decreased GS and DCGS. Despite this, Allograft Life Years were gained even with longer CITs, demonstrating the utility of using these allografts. [ABSTRACT FROM AUTHOR]

The influence of African American (AA) recipient race on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) is uncertain. Methods: From 11/01 to 2/19, we retrospectively studied 158 Caucasian (C) and 57 AA patients (pts) undergoing SPKT. Results: The AA group had fewer patients on peritoneal dialysis (30% C vs. 14% AA), more patients with longer dialysis duration (28% C vs. 51% AA), more sensitized (PRA ≥20%) patients (6% C vs. 21% AA), and more patients with pretransplant C‐peptide levels ≥2.0 ng/ml (11% C vs. 35% AA, all P <.05). With a mean 9.2 year follow‐up, patient survival (65% C vs. 77% AA, P =.098) slightly favored the AA group, whereas kidney (55% C vs. 60% AA) and pancreas (48% C vs. 54% AA) graft survival rates (GSRs) were comparable. Death‐censored kidney (71% C vs. 68% AA) and pancreas (both 62%) GSRs demonstrated that death with a functioning graft (DWFG) was more common in C vs. AA patients (23% C vs. 12% AA, P =.10). The incidence of death‐censored dual graft loss (usually rejection) was 7% C versus 21% AA (P =.005). Conclusions: Following SPKT, AA patients are at a greater risk for dual immunological graft loss whereas C patients are at greater risk for DWFG. [ABSTRACT FROM AUTHOR]

Following simultaneous pancreas‐kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C‐peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp‐]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp‐ (level < 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5‐year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p =.15), and pancreas graft survival (60% versus 86%, p =.03) rates were lower in Cp+ versus Cp‐ patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp‐, p =.026) or rejection (17% Cp+ versus 6.5% Cp‐, p =.2). Post‐transplant weight gain > 5 kg occurred in 72% of Cp+ versus 26% of Cp‐ patients (p =.0001). In patients with functioning grafts, mean one‐year post‐transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp‐) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp‐). In this matched case‐control study, outcomes were inferior in Cp+ compared to Cp‐ patients following SPKT, with post‐transplant weight gain, insulin resistance, and rejection as potential mitigating factors. [ABSTRACT FROM AUTHOR]

The influence of recipient age on outcomes following simultaneous pancreas‐kidney transplantation (SPKT) in the modern era is uncertain. Methods: We retrospectively studied 255 patients undergoing SPKT from 11/01 to 8/20. Recipients were stratified according to age group: age <30 years (n = 16); age 30–39 years (n = 91); age 40–49 years (n = 86) and age ≥50 years (n = 62 [24.3%], including 9 patients ≥60 years of age). Results: Three‐month and one‐year outcomes were comparable. The eight‐year patient survival rate was lowest in the oldest age group (47.6% vs 78% in the 3 younger groups combined, p <.001). However, eight‐year kidney and pancreas graft survival rates were comparable in the youngest and oldest age groups combined (36.5% and 32.7%, respectively), but inferior to those in the middle 2 groups combined (62% and 50%, respectively, both p <.05). Death‐censored kidney and pancreas graft survival rates increased from youngest to oldest recipient age category because of a higher incidence of death with functioning grafts (22.6% in oldest group compared to 8.3% in the 3 younger groups combined, p =.005). Conclusions: Recipient age did not appear to significantly influence early outcomes following SPKT. Late outcomes are similar in younger and older recipients, but inferior to the middle 2 age groups. [ABSTRACT FROM AUTHOR]

Two renal‐risk variants in the apolipoprotein L1 gene (APOL1) in African American (AA) deceased donors (DD) are associated with shorter renal allograft survival after transplantation. To identify additional genes contributing to allograft survival, a genome‐wide association study was performed in 532 AA DDs. Phenotypic data were obtained from the Scientific Registry of Transplant Recipients. Association and single‐nucleotide polymorphism (SNP)‐by‐APOL1 interaction tests were conducted using death‐censored renal allograft survival accounting for relevant covariates. Replication and inverse‐variance‐weighted meta‐analysis were performed using data from 250 AA DD in the Genomics of Transplantation study. Accounting for APOL1, multiple SNPs near the Nudix Hydrolase 7 gene (NUDT7) showed strong independent effects (P = 1.6 × 10−8‐2.2 × 10−8). Several SNPs in the Translocation protein SEC63 homolog (SEC63; P = 2 × 10−9‐3.7 × 10−8) and plasmacytoma variant translocation 1 (PVT1) genes (P = 4.0 × 10−8‐7 × 10−8) modified the effect of APOL1 on allograft survival. SEC63 is expressed in human renal tubule cells and glomeruli, and PVT1 is associated with diabetic kidney disease. Overall, associations were detected for 41 SNPs (P = 2 × 10−9‐5 × 10−8) contributing independently or interacting with APOL1 to impact renal allograft survival after transplantation from AA DD. Given the small sample size of the discovery and replication sets, independent validations and functional genomic efforts are needed to validate these results. [ABSTRACT FROM AUTHOR]

Abstract: To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single‐center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20‐30 hours, 52 patients; (iii) 30‐40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow‐up of 48 months, overall patient and graft survival rates were 91% and 81%. Death‐censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4‐year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. [ABSTRACT FROM AUTHOR]

Background The value of importing expanded criteria donor ( ECD) kidneys is uncertain. Methods We retrospectively reviewed our single-center experience with ECD kidney transplants ( KT). Results Over 12.8 years, we performed 497 ECD KTs including 247 local and 250 imported from other donor service areas. The import ECD group had more donors (16% vs 9%) ≥ age 70, more zero human leukocyte antigen mismatches (14% vs 2%), more KTs with a cold ischemia time >30 hours (46% vs 19%), and fewer kidneys managed with pump preservation (78% vs 92%, all P≤.05) compared to the local ECD group. Mean Kidney Donor Profile Index were 80% import vs 84% local. With a mean follow-up of 55 months, actual patient and graft survival rates were 71% and 58% in import vs 76% and 58% in local ECD KTs, respectively. Death-censored graft survival rates were 70% in import vs 69% in local ECD KTs. Delayed graft function occurred in 28% import vs 23% local ECD KTs ( P=NS) whereas the incidence of primary nonfunction was slightly higher with import ECD kidneys (4.8% vs 2.4%, P=.23). Conclusions Midterm outcomes are remarkably similar for import vs local ECD KTs, suggesting that broader sharing of ECD kidneys may improve utilization without compromising outcomes. [ABSTRACT FROM AUTHOR]

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH) and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement. [ABSTRACT FROM AUTHOR]