Calcineurin inhibitor (CNI) nephrotoxicity may occur any time after initiation of therapy, and can affect transplant or native kidneys and present as acute or chronic reductions in kidney function. Elevated serum CNI trough levels may help make the diagnosis, although CNI nephrotoxicity is not necessarily dose dependent. CNI can cause vasoconstriction and increased serum creatinine (Scr) in the absence of morphologic findings, so CNI toxicity can be suggested as the cause of an abrupt Scr rise without morphologic changes.