Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation

Abstract

BackgroundBiopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented.MethodsPatients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18–39 years (young), 40–55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease.ResultsRejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up).ConclusionRejection is a major cause of graft loss but recipient’s age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.

Tacrolimus Monotherapy is Safe in Immunologically Low-Risk Kidney Transplant Recipients: A Randomized-Controlled Pilot Study

“…This side-effect was believed to be the most important cause for a relative lack in improvement of long-term graft patency observed after introduction of CNI. Most recent studies however, have pointed to chronic humoral rejection as the major cause for long-term graft failure and stress the importance of adequate trough levels and low intrapatient variability (15)(16)(17)(18)(19). Tacrolimus with trough levels above 5.0 ug/L have indeed been associated with improved graft survival (20,21).…”

The number of donor HLA-derived T cell epitopes available for indirect antigen presentation determines the risk for vascular rejection after kidney transplantation

“…Recently, there is a renewed interest in the long-term negative effects of TCMR. Even after T cell-depleting therapy, a definitive resolution of the rejection is sometimes not achieved and graft loss may follow in the years thereafter ( 1 , 2 , 22 ). Hence, a better understanding of clinical relevant HLA mismatches and mechanisms involved is still needed.…”

“…Although the incidence of acute T cell-mediated rejection (aTCMR) after kidney transplantation has decreased over the last decades by more potent immune suppressive drugs, aTCMR still contribute significantly to the incidence of graft loss ( 1 , 2 ). The immunological mechanism of aTCMR is characterized by cytotoxic CD8 + cells that recognize intact mismatched HLA class-I proteins on donor cells, a mode of recognition known as the direct pathway of allorecognition.…”

Extracellular Vesicles: The Future of Diagnosis in Solid Organ Transplantation?

“…Kidney graft rejection is the main cause of graft failure censored for death at any time following transplantation [ 75 ]. According to some series, the incidence of ABMR increases over time at a rate of 1.1% per year, while TCMR is rare 6 years after transplantation [ 75 ].…”