Exploring the Complexity of Death-Censored Kidney Allograft Failure

• Published in: Journal of the American Society of Nephrology 2021-06, Vol.32 (6), p.1513-1526
• Main Authors: Mayrdorfer, Manuel, Liefeldt, Lutz, Wu, Kaiyin, Rudolph, Birgit, Zhang, Qiang, Friedersdorff, Frank, Lachmann, Nils, Schmidt, Danilo, Osmanodja, Bilgin, Naik, Marcel G, Duettmann, Wiebke, Halleck, Fabian, Merkel, Marina, Schrezenmeier, Eva, Waiser, Johannes, Duerr, Michael, Budde, Klemens
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allografts - pathology; Allografts - physiopathology; Allografts - statistics & numerical data; Calcineurin Inhibitors - adverse effects; Cardio-Renal Syndrome - complications; Clinical Research; Databases, Factual; Death; Female; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival; Humans; Immunity, Cellular; Immunity, Humoral; Immunosuppressive Agents - therapeutic use; Kidney Failure, Chronic - surgery; Kidney Transplantation - standards; Kidney Transplantation - statistics & numerical data; Male; Medication Adherence - statistics & numerical data; Middle Aged; Polyomavirus Infections - complications; Recurrence; Retrospective Studies; Survival Rate; T-Lymphocytes; Thrombosis - complications; Time Factors; Tumor Virus Infections - complications
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2020081215

Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. 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. 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. GL is often multifactorial and more complex than previously thought.