Over 35 years of use has demonstrated the revolutionary therapeutic benefits of calcineurin inhibitors (CNI) in not only preventing transplant rejection, but also the renal and nonrenal toxicity of CNI. Acute reversible and insidious irreversible forms of CNI nephrotoxicity have been identified, with ischemia from an imbalance between vasoconstrictors and vasodilators playing an important role. The ongoing search to define toxicity pathways has been enriched by 'Omics' studies. Changes in proteins including those involved in activation of pro-inflammatory responses, oxidative stress, ER stress and the unfolded protein response have been identified, and these may serve as biomarkers of toxicity. However, the current standard of CNI toxicity, histology, lacks specificity, which creates challenges for biomarker validation. This review focuses on progress in nephrotoxic pathway identification of CNI and biomarker validation.
Keywords: biomarkers; calcineurin inhibitors; cyclophylins; cyclosporine; nephrotoxicity; tacrolimus.