[Monitoring of calcineurin inhibitors induced-nephrotoxicity].
Chronic allograft nephropathy is characterized by an increase over time of interstitial fibrosis, tubular atrophy, fibrointimal thickening, arteriolar hyalinosis and glomerulosclerosis, resulting in progressive renal dysfunction. It is mainly caused by calcineurin inhibitors-induced nephrotoxicity, which is related to an imbalance between vasoconstrictor and vasodilator factors. Cyclosporine A-induced nephrotoxicity is particularly due to the activation of pro-apoptotic genes leading to tubular atrophy with tubular cell apoptosis and to hemodynamic changes inducing interstitial fibrosis by the activation of factors stimulating the fibroblast proliferation (TGFbeta, Endothelin-A and Plasminogen activator inhibitor-1). Calcineurin inhibitors (CNI) treatment monitoring is essentially based on histology, but a better follow-up of drug exposure post-transplantation leading to a regular and rapid adjustment of the doses to avoid extended periods of overexposure, could enable to decrease their nephrotoxicity and improve graft survival in treated patients. CNIs dose reduction or conversion to proliferating signal inhibitors may be a therapeutic alternative.
Kamar
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Service de Néphrologie, Dialyse et Transplantation d'organes, CHU de Toulouse-Rangueil, 1, avenue Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 09, France. kamar.n@chu-toulouse.fr
Rostaing
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D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D016903:Drug Monitoring; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000139:chemically induced*
D065095:Calcineurin Inhibitors