Anti-Diabetogenic Properties of Mineralocorticoid Receptor Antagonists: Implications for Enhanced Safety and Efficacy of Post-Transplantation Pharmacotherapies

Widespread usage of the calcineurin inhibitors tacrolimus and cyclosporine A as post-transplantation immunosuppressive agents is fraught with severe nephrotoxic and diabetogenic side effects. More recently, tapering of calcineurin inhibitor-based immunotherapies with concurrent administration of the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus has been employed within pharmacological regimens designed to achieve better safety and efficacy for preservation of allograft kidney function. Collected preclinical data and recent clinical study, however, indicate that usage of calcineurin inhibitors and/or mTOR blockers as immunosuppressive agents promotes equivalent diabetogenic side effects. Based on a wealth of validating preclinical studies, we contend that the favorable metabolic effects of mineralocorticoid receptor antagonists, such as spironolactone, support their inclusion in novel immunosuppressive strategies to inhibit new onset type II diabetic symptoms in post-transplantation patient populations.