292.5 - Analysis of Calcineurin Toxicity by Single-Nephron Omics
Monday, April 4, 2022
2:05 PM – 2:20 PM
Room: Ballroom A - Pennsylvania Convention Center
Introduction: Calcineurin inhibitors (CNI), such as cyclosporine A, tacrolimus, or newly generated voclosporin, belong to first choice immunosuppressive strategies for prevention of allograft rejection in patients undergoing organ transplantation. CNI are also instrumental in management of autoimmune diseases including lupus nephritis and atopic dermatitis. Although CNI have dramatically improved the quality of patient care, therapeutic benefits are limited by detrimental consequences on the renal and cardiovascular systems. Hypertension, electrolyte disorders, hyperlipidemia, and new-onset diabetes mellitus have been frequently reported in patients receiving CNI. While the immunosuppressive effects of CNI rely on impeding calcineurin-dependent activation of T-lymphocytes, numerous side effects have been linked to loss of calcineurin signaling in the kidney or heart. An emerging concept suggests that immunosuppression and renal side effects may be mediated by inhibition of distinct isoforms of the calcineurin catalytic subunit. Furthermore, CNI have targets that are independent on calcineurin. Improved understanding of mechanisms underlying the CNI-induced toxicity may promote generation of novel strategies that efficiently blunt the immune response while circumventing the renal and cardiovascular damage. The goal of the proposed symposium is to highlight recent strides in this direction.
