Comparable kidney transplant outcomes in selected patients with a body mass index ≥ 40: A personalized medicine approach to recipient selection.

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.

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.

Analyzing outcomes following pancreas transplantation: Definition of a failure or failure of a definition.

Pancreas transplantation has an identity crisis and is at a crossroads. Although outcomes continue to improve in each successive era, the number of pancreas transplants performed annually in the United States has been static for several years in spite of increasing numbers of deceased donors. For most practitioners who manage diabetes, pancreas transplantation is considered an extreme measure to control diabetes. With expanded recipient selection (primarily simultaneous pancreas-kidney transplantation) in patients who are older, have a higher BMI, are minorities, or who have a type 2 diabetes phenotype, the controversy regarding type of diabetes detracts from the success of intervention. The absence of a clear and precise definition of pancreas graft failure, particularly one that lacks a measure of glycemic control, inhibits wider application of pancreas transplantation with respect to reporting long-term outcomes, comparing this treatment to alternative therapies, developing listing and allocation policy, and having a better understanding of the patient perspective. It has been suggested that the definition of pancreas graft failure should differ depending on the type of pretransplant diabetes. In this commentary, we discuss current challenges regarding the development of a uniform definition of pancreas graft failure and propose a potential solution to this vexing problem.

Does prolonged cold ischemia affect outcomes in donation after cardiac death donor kidney transplants?

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.

Improved surgical outcomes following simultaneous pancreas-kidney transplantation in the contemporary era.

BACKGROUND: Complications leading to early technical failure have been the Achilles' heel of simultaneous pancreas-kidney transplantation (SPKT). The study purpose was to analyze longitudinally our experience with early surgical complications following SPKT with an emphasis on changes in practice that improved outcomes in the most recent era. STUDY DESIGN: Single center retrospective review of all SPKTs from 11/1/01 to 8/12/20 with enteric drainage. Early relaparotomy was defined as occurring within 3 months of SPKT. Patients were stratified into two sequential eras: Era 1 (E1): 11/1/01-5/30/13; Era 2 (E2) 6/1/13-8/12/20 based on changes in practice that occurred pursuant to donor age and pancreas cold ischemia time (CIT). RESULTS: 255 consecutive SPKTs were analyzed (E1, n = 165; E2, n = 90). E1 patients received organs from older donors (mean E1 27.3 vs. E2 23.1 years) with longer pancreas cold CITs) (mean E1 16.1 vs. E2 13.3 h, both p < .05). E1 patients had a higher early relaparotomy rate (E1 43.0% vs. E2 14.4%) and were more likely to require allograft pancreatectomy (E1 9.1% vs. E2 2.2%, both p < .05). E2 patients underwent systemic venous drainage more frequently (E1 8% vs. E2 29%) but pancreas venous drainage did not influence either relaparotomy or allograft pancreatectomy rates. The most common indications for early relaparotomy in E1 were allograft thrombosis (11.5%) and peri-pancreatic phlegmon/abscess (8.5%) whereas in E2 were thrombosis, pancreatitis/infection, and bowel obstruction (each 3%). CONCLUSION: Maximizing donor quality (younger donors) and minimizing pancreas CIT are paramount for reducing early surgical complications following SPKT.

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.

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.

Molecular Pathways Underlying Adaptive Repair of the Injured Kidney: Novel Donation After Cardiac Death and Acute Kidney Injury Platforms.

OBJECTIVE: To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration. BACKGROUND: Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery. METHODS: Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays. RESULTS: Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days. CONCLUSIONS: Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation.

C-peptide levels do not correlate with pancreas allograft failure: Multicenter retrospective analysis and discussion of the new OPT definition of pancreas allograft failure.

The OPTN Pancreas Transplantation Committee performed a multicenter retrospective study to determine if undetectable serum C-peptide levels correspond to center-reported pancreas graft failures. C-peptide data from seven participating centers (n = 415 graft failures for transplants performed from 2002 to 2012) were analyzed pretransplant, at graft failure, and at return to insulin. One hundred forty-nine C-peptide values were submitted at pretransplant, 94 at return to insulin, and 233 at graft failure. There were 77 transplants with two available values (at pretransplant and at graft failure). For recipients in the study with pretransplant C-peptide <0.75 ng/mL who had a posttransplant C-peptide value available (n = 61), graft failure was declared at varying levels of C-peptide. High C-peptide values at graft failure were not explained by nonfasting testing or by individual center bias. Transplant centers declare pancreas graft failure at varying levels of C-peptide and do not consistently report C-peptide data. Until February 28, 2018, OPTN did not require reporting of posttransplant C-peptide levels and it appears that C-peptide levels are not consistently used for evaluating graft function. C-peptide levels should not be used as the sole criterion for the definition of pancreas graft failure.

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

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.

Eversion endarterectomy of the deceased donor renal artery to prevent kidney discard.

INTRODUCTION: Deceased donor (DD) kidneys exhibiting severe atherosclerosis involving the renal artery (RA) may represent a contraindication to kidney transplantation (KT). METHODS: Eversion endarterectomy (EE) was performed as a salvage procedure to permit KT. RESULTS: We identified 17 cases (1.2% of all DD KTs during the study period) involving EE of the DD RA. Thirteen (76.5%) kidneys were imported, and mean Kidney Donor Profile Index (KDPI) was 81%. Mean DD age was 59 years, mean RA plaque length was 1.7 cm, and mean glomerulosclerosis on biopsy was 10%. Mean recipient age was 64 years, and dialysis vintage was 32 months. With a mean follow-up of 36 months, actual patient and graft survival rates were both 76.5%. One patient died early without a technical problem. Of the remaining 16 patients, 2-year patient and graft survival rates were both 100%. There were no early or late vascular complications. The incidence of delayed graft function was 35%. Mean serum creatinine and GFR levels in patients with functioning grafts at latest follow-up were 1.8 mg/dL and 40 mL/min, respectively. CONCLUSIONS: EE appears to be a safe and under-utilized procedure that may prevent discard of marginal donor kidneys and is associated with acceptable short-term outcomes.

Analysis of local versus imported expanded criteria donor kidneys: A single-center experience with 497 ECD kidney transplants.

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.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

BACKGROUND: The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. STUDY DESIGN: We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. RESULTS: Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for patients receiving single KTs. CONCLUSIONS: Dual kidney transplantation using kidneys from adult marginal DDs that otherwise might be discarded offer a viable option to counteract the growing shortage of acceptable single kidneys. Excellent medium-term outcomes can be achieved and waiting times can be reduced in a predominantly older recipient population.

Deceased donor multidrug resistance protein 1 and caveolin 1 gene variants may influence allograft survival in kidney transplantation.

Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft failure were performed for the 1233 resultant kidney transplantations, adjusting for recipient age, sex, ethnicity, cold ischemia time, panel reactive antibody, human leukocyte antigen match, expanded-criteria donation, and APOL1-nephropathy variants in AA donors. Interaction analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of all transplantations, ABCB1 index SNP rs1045642 was associated with time to allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1 SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors. Interactions between ABCB1 and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from AA donors.

Simultaneous transplantation of the living donor kidney and deceased donor pancreas and other transplant options for diabetic and uremic patients.

PURPOSE OF REVIEW: Solitary deceased donor kidney and simultaneous pancreas and kidney (SPK) transplantation are the two most common transplant procedures performed for patients with diabetes and uremia, vastly outnumbering all other organ replacement options. Given the improvement in outcomes for solitary pancreas transplantation, the higher mortality for diabetic patients on the waiting list, and the growing shortage of organs (particularly kidneys) for transplantation, the use of living donors for this complex patient population should be more common. RECENT FINDINGS: Yet, despite some clear advantages, sequential pancreas after live donor kidney transplant and especially the combined procedure, simultaneous pancreas (from a deceased donor) and living donor kidney transplantation are relatively uncommon. SUMMARY: Possible reasons for the infrequent use of these options and methods for increasing the use of living donor kidneys for the diabetic and uremic patient are presented.