Challenges in diagnosing acute calcineurin-inhibitor induced nephrotoxicity: from toxicogenomics to emerging biomarkers.

Use of calcineurin inhibitors (CNIs) for immunosuppression after transplantation induces vasoconstriction of renal afferent arterioles, leading to functional changes and potentially irreversible chronic ischemic structural damage. Because CNI-induced nephrotoxicity is strongly suspected in many renal allografts and significantly contributes to interstitial fibrosis and tubular atrophy, better tests are needed to diagnose nephrotoxicity in its early stages. However, despite intensive research efforts, no reliable test is currently available that can accurately and specifically diagnose early CNI nephrotoxicity. An early diagnosis might prompt a switch to agents with a beneficial effect on renal function. This paper is a review of recent progress in toxicogenomic studies that has led to identification of epithelial-to-mesenchymal transition and endoplasmic reticulum stress as potential early markers of tubular cell response to CNI-induced injury. Detection of epithelial-to-mesenchymal transition and/or endoplasmic reticulum stress markers could help diagnose early CNI nephrotoxicity and lead to modification of the immunosuppressive regimen by replacement of CNIs with drugs that have a more acceptable toxicity profile.