Exploring the Complexity of Death-Censored Kidney Allograft Failure

Abstract

BackgroundFew studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance.MethodsA novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL.ResultsIn 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell–mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time.ConclusionsGL is often multifactorial and more complex than previously thought.

Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring

“…dnDSA formation at post-transplantation is the leading cause of developing chronic antibody-mediated (cABMR) rejection (8,9); they have a particularly worse impact upon kidney allograft survival especially when they bind complement, i.e., either C1q (9,10) or C3d (11) components. Recently, Mayrdorfer et al have reassessed the causes of kidney allograft failure in the modern immunosuppression era in a prospective cohort of 1,642 kidney transplant (KTx) recipients (12). They found that in 51.2% of patients with allograft failure, more than one cause was involved.…”

Death With Function and Graft Failure After Kidney Transplantation: Risk Factors at Baseline Suggest New Approaches to Management

“…Mayrdorfer et al found that alloimmunity accounted for 64.7% of graft losses (T cell–mediated rejection in 34% and AMR in 30.7%). 8 Medical causes accounted for only 36.3%. Chand et al found that 42.3% of their 97 cases of GF beyond 1 mo were due to alloimmunity.…”

Pure T-cell mediated rejection following kidney transplant according to response to treatment

“…Late TCMR has been suggested as a predictor of low GS in previous studies [27,28]. Recently, Mayrdorfer et al suggested that TCMR might be a contributing factor in about one-third of early and late graft failures [29]. For over a long term after transplantation, nonimmunologic factors, including chronic toxicity, had great importance in graft function [30].…”