Allograft Function In Kidney Transplantation Research Articles

Donor Proteinuria and Allograft Function in Kidney Transplantation: Short- and Long-Term Results From a Retrospective Cohort Study.

Donor proteinuria (DP) is a common but rarely evaluated aspect of today's kidney transplant allocation process. While proteinuria after kidney transplantation is a risk factor for impaired graft function and survival, the long-term effects of DP in kidney transplantation have not yet been evaluated. Therefore, this study aims to investigate the impact of DP on the long-term outcome after kidney transplantation. A total of 587 patients were found to be eligible and were stratified into two groups: (1) those receiving a graft from a donor without proteinuria (DP-) and (2) those receiving a graft from a donor with proteinuria (DP+). At 36months, there was no difference in the primary composite endpoint including graft loss and patient survival (log-rank test, p = 0.377). However, the analysis of DP+ subgroups showed a significant decrease in overall patient survival in the group with high DP (p = 0.017). DP did not adversely affect patient or graft survival over 36months. Nevertheless, this work revealed a trend towards decreased overall survival of patients with severe proteinuria in the subgroup analysis. Therefore, the underlying results suggest caution in allocating kidneys from donors with high levels of proteinuria.

Plasma protein signatures reflect systemic immunity and allograft function in kidney transplantation

Kidney transplantation causes large perturbations of the immune system. While many studies focus on the allograft, insights into systemic effects are largely missing. Here, we analyzed the systemic immune response in 3 cohorts of kidney transplanted patients. Using serum proteomics, laboratory values, mass cytometry, histological and clinical parameters, inter-patient heterogeneity was leveraged for multi-omic co-variation analysis. We identified circulating immune modules (CIM) that describe extra-renal signatures of co-regulated plasma proteins. CIM are present in nontransplanted controls, in transplant conditions and during rejection. They are enriched in pathways linked to kidney function, extracellular matrix, signaling, and cellular activation. A complex leukocyte response in the blood during allograft quiescence and rejection is associated with CIM activity and CIM-specific cytokines. CIM activity correlates with kidney function including a 2-month prediction. Together, the data suggest a systemic and multi-layered response of transplant immunity that might be insightful for understanding allograft dysfunction and developing translational biomarkers.

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review.

Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers’ profiling complications after kidney transplantation.

Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial.

BackgroundThis randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT).Material/MethodsSeventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the “EVL group” (n=38) and the “TAC group” (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group.ResultsThe 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively).The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group.ConclusionsEVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.

The interaction between post-transplant anemia and allograft function in kidney transplantation: The Japan Academic Consortium of Kidney Transplantation-II study.

The interaction between post-transplant anemia (PTA) and allograft function in kidney transplantation has not been evaluated directly. PTA, defined by WHO/AST criteria, was investigated in 1307 adult kidney transplant recipients between 2000 and 2015 (median follow-up, 7years). We investigated the impact of hemoglobin (Hb) on graft failure (non-censored for death) and their interactions, time-dependent Cox model, and subgroup analysis were used. PTA prevalence was 43.6% at 7years and varied according to allograft function, recipient sex, and follow-up period. Decreased Hb considering the time-varying effect was associated with an increased risk of graft failure (hazard ratio = 1.83, 95% CI 1.66-2.02, P < 0.001). In subgroup analysis, allograft function (post-transplant time-averaged estimated glomerular filtration rate and cut point: 45mL/min/1.73m2) had significant interaction (P = 0.032). The 7-year graft failure rate in recipients with PTA and high eGFR was 7.7% (HR 1.52, 95% CI 1.25-1.84), whereas in those with PTA and low eGFR was 19.9% (HR 2.00, 95% CI 1.74-2.31). The unfavorable impact of PTA was significantly enhanced by low allograft function. PTA is likely to be associated with graft failure due to interaction with allograft function. Therefore, we should consider both Hb level and allograft function while determining the treatment strategy.