Chronic Calcineurin Inhibitor Nephrotoxicity: Reflections on an Evolving Paradigm

Use of the calcineurin inhibitors (CND cyclosporine and tacrolimus has revolutionized solid organ transplantation. For more than 30 yr, the transplant community has dealt with nephrotoxicity attributed to these agents. Acute renal vasoconstriction (as described by many investigators, including John Curtis and colleagues) is the unequivocal consequence of their use; chronic CNI nephropathy, although indistinct in terms of histology and pathophysiology, has become accepted as a major cause of late kidney allograft failure. This article examines clinical, laboratory, and histologic findings that evolved into a paradigm that was never fully consistent with observed outcomes and new evidence that may offer an alternative interpretation for adverse events that are attributed to CNI nephrotoxicity in kidney transplant recipients. Clin I Am Soc Nephrol 4: 2029-2034, 2009 doi 10 2215/CJN 03820609