Effects of calcineurin inhibition on renal tubular transport

Calcineurin inhibitors (CNIs), including tacrolimus and cyclosporin A, are potent immunosuppressive drugs that exert their effects by inhibiting protein phosphatase 3, also known as calcineurin. CNIs are widely used clinically, particularly for preventing organ rejection following transplantation. However, their use is frequently associated with significant adverse effects. In particular, CNIs commonly affect the kidney and can lead to acute and chronic kidney injury. In addition, they interfere with renal electrolyte reabsorption resulting in electrolyte disturbances (e.g., hyperkalemia and hypomagnesemia) and hypertension. Notably, calcineurin subunits are abundantly expressed throughout the nephron. Consequently, calcineurin inhibition affects electrolyte transport in virtually all nephron segments. In this review, we summarize the current knowledge on the effects of CNIs on renal tubular ion transport processes and highlight the underlying mechanism by which these effects contribute to CNI-induced electrolyte disturbances.