Exploring the Complexity of Death-Censored Kidney Allograft Failure

Significance Statement Stagnating long-term outcomes are a persistent obstacle for the transplant community, but surprisingly, large contemporary studies investigating the causes of graft failure are rare. However, it is obvious that a thorough analysis of graft failures is the first step to improve outcomes. A study that is on the basis of a database designed and implemented for kidney transplant recipients over 20 years ago and an active effort to keep allograft recipients in the post-transplant care program reveals previously overlooked information that leads to insights into the complexity of allograft failure. These include the effect of T cell–mediated rejection, the role of antibody-mediated rejection in late graft failure, and the influence of recipient age on the causes of graft failure. Background Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. Methods A 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. Results In 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. Conclusions GL is often multifactorial and more complex than previously thought.