Challenges and considerations in diagnosing the kidney disease in deteriorating graft function

Summary Despite significant reductions in acute‐rejection rates with the introduction of calcineurin inhibitor (CNI)‐based immunosuppressive therapy, improvements in long‐term graft survival in renal transplantation have been mixed. Improving long‐term graft survival continues to present a major challenge in the management of kidney‐transplant patients. CNIs are a key component of immunosuppressive therapy, and chronic CNI toxicity has been widely thought to be a major factor in late graft failure. However, recent studies examining the causes of late graft failure in detail have challenged this view, highlighting the importance of antibody‐mediated rejection and other factors. In addition, the diagnosis of CNI nephrotoxicity represents a challenge to clinicians, with the potential for over‐diagnosis and an inappropriate reduction in immunosuppressive therapy. When graft function is deteriorating, accurately determining the cause of the kidney disease is essential for effective long‐term management of the patient. Diagnosis requires a thorough clinical investigation, and in the majority of cases a specific cause can be identified.