Biomarkers of Calcineurin Inhibitor Nephrotoxicity in Transplantation

Abstract

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

Financial & competing interests disclosure

Z Endre has received honoraria as a member of Novartis Medical Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Z Endre has received honoraria as a member of Novartis Medical Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.