Single center experience and literature review of kidney transplantation from non-ideal donors with acute kidney injury: Risk and reward.

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.

Long-term outcomes of kidney transplantation from deceased donors with terminal acute kidney injury: Single center experience and literature review.

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.

Influence of donor and recipient sex on outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature.

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.

Does dialysis modality or duration influence outcomes in simultaneous pancreas-kidney transplant recipients? Single center experience and review of the literature.

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.

Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study.

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.

Simultaneous pancreas-kidney transplantation in Caucasian versus African American patients: Does recipient race influence outcomes?

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.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation.

BACKGROUND: African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. METHODS: Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. RESULTS: Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. CONCLUSION: Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Recipient age and outcomes following simultaneous pancreas-kidney transplantation in the new millennium: Single-center experience and review of the literature.

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.

The Kidney Not Taken: Single-Kidney Use in Deceased Donors.

BACKGROUND: The nonuse rate for kidneys recovered from deceased donors is increasing, rising to 27% in 2023. In 10% of these cases, 1 kidney is transplanted but the mate kidney is not. STUDY DESIGN: We conducted a retrospective, single-center cohort study from December 2001 to May 2023 comparing single kidneys transplanted at our center (where the contralateral kidney was not used) to kidneys where both were transplanted separately, at least 1 of which was at our center. RESULTS: We performed 395 single deceased-donor kidney transplants in which the mate kidney was not transplanted. Primary reasons for mate kidney nonuse were as follows: no recipient located or list exhausted (33.4%), kidney trauma or injury or anatomic abnormalities (18.7%), biopsy findings (16.7%), and poor renal function (13.7%). Mean donor and recipient ages were 51.5 ± 14.2 and 60 ± 12.6 years, respectively. Mean kidney donor profile index was 73% ± 22%, and 104 donors (26.3%) had kidney donor profile index >85%. Mean cold ischemia was 25.6 ± 7.4 hours, and 280 kidneys (70.7%) were imported. Compared with 2,303 concurrent control transplants performed at our center, primary nonfunction or thrombosis (5.1% single vs 2.8% control) and delayed graft function (35.4% single vs 30.1% control) were greater with single-kidney use (both p < 0.05). Median patient and death-censored graft survival were shorter in the single group (11.6 vs 13.5 years, p = 0.03 and 11.6 vs 19 years, p = 0.003), although the former was at least double median survival on the waiting list. In patients with functioning grafts in the single-kidney group, 1-year mean serum creatinine was 1.77 ± 0.8 mg/dL and estimated glomerular filtration rate was 44.8 ± 20 mL/min/1.73 m 2 . CONCLUSIONS: These findings suggest that many mate kidneys are being inappropriately rejected, given the acceptable outcomes that can be achieved by transplanting the single kidney in appropriately selected recipients.

Scope and Consistency of Cancer Outcomes Reported in Randomized Trials in Kidney Transplant Recipients.

Introduction: Cancer is an important outcome in kidney transplantation, but the scope and consistency of how cancer is defined and reported in trials involving kidney transplant recipients has not been evaluated. This study aimed to assess the range and variability of cancer outcomes in trials involving kidney transplant recipients. Methods: The ClinicalTrials.gov database was searched from February 2000 to July 2021 to identify all randomized controlled trials (RCTs) in adult kidney transplant recipients, and which included cancer as a specified outcome. The definition of cancer, types of cancer (if any), timepoint(s) of measurement and method of aggregation were extracted for each cancer outcome. Results: Of the 819 trials in kidney transplantation, only 84 (10%) included 1 or more cancer outcomes. Of these, 72 of 84 (86%) trials included cancer as a secondary outcome and 12 of 84 (14%) considered cancer as a primary outcome. The most frequent description of cancer was "malignancy" (n = 44, 43%), without reference to diagnostic criteria, histology, grade, or stage. The 2 most common cancer types were posttransplant lymphoproliferative disorder (PTLD) (n = 20, 20%) and nonmelanoma skin cancer (n = 10, 10%). Several methods of aggregation were identified, including incidence or rate (n = 47, 46%), frequency or proportion (n = 30, 29%), and time to event (n = 5, 5%). Approximately half the cancer outcomes were measured at a single time point (n = 44, 52%). Conclusion: Cancer is an infrequently reported outcome and is inconsistently defined in trials of kidney transplant recipients. Consistent reporting of cancer outcomes using standardized definitions would provide important information on the impact of cancer in patients after kidney transplantation.

Practical Considerations for APOL1 Genotyping in the Living Kidney Donor Evaluation.

BACKGROUND: Association between the apolipoprotein L1 gene (APOL1) and nephropathy has altered the epidemiology of chronic kidney disease. In addition, donor APOL1 genotypes play important roles in the time to allograft failure in kidneys transplanted from deceased donors and the safety of living kidney donation. METHODS: This article reviews genetic testing for inherited kidney disease in living kidney donors to improve donor safety. APOL1 genotyping in donors with recent African ancestry is considered. RESULTS: Based on current data, transplant physicians should discuss APOL1 genotyping with potential living kidney donors self-reporting recent African ancestry. Until results from APOL1 Long-term Kidney Transplant Outcomes Network ancillary studies are available, we present practical approaches from our experience for considering APOL1 genotyping in the living donor evaluation. CONCLUSIONS: Transplant physicians should inform potential living kidney donors at risk for APOL1-associated nephropathy about the gene and possibility of genetic testing early in the donor evaluation, well before scheduling the donor nephrectomy. Transplant programs must weigh risks of performing a donor nephrectomy in those with 2 APOL1 renal risk variants (high-risk genotypes), particularly younger individuals. Our program counsels kidney donors with APOL1 high-risk genotypes in the same fashion as with risk genotypes in other nephropathy genes. Because most African American kidney donor candidates lacking hypertension, proteinuria and reduced kidney function after workup will not possess APOL1 high-risk genotypes, genetic testing is unlikely to markedly increase donor declines and may reassure donors with regard to their long-term kidney outcomes, potentially increasing the number of African American donors.

Two transplant renal arteries: One important lesson.

High index of suspicion is required for ischemic nephropathy in renal transplant recipients presenting with unexplained acute kidney injury, as it is potentially reversible. Carbon dioxide (CO2) angiogram is a good alternative to evaluate vasculature in patients with renal dysfunction where iodinated contrast is relatively contraindicated.