The pharmacogenetics of calcineurin inhibitor-related nephrotoxicity.
Chronic calcineurin inhibitor (CNI)-induced nephrotoxicity is associated with prolonged use of cyclosporine and tacrolimus and has been observed after all types of transplantation, as well as during treatment of autoimmune disease. Extensive alterations in the renal architecture including glomerular sclerosis, tubular atrophy and interstitial fibrosis may lead to end-stage renal failure. Increasing evidence shows that pharmacogenetic factors explain part of the between-patient differences in susceptibility to developing CNI-induced nephrotoxicity. In this paper this evidence is reviewed, with special emphasis on the role of genetic factors influencing metabolism and transportation of CNIs in both acceptor and donor.
Hesselink
Dennis A
DA
Department of Internal Medicine, Division of Nephrology and Renal Transplantation, Erasmus MC, Rotterdam, The Netherlands. d.a.hesselink@erasmusmc.nl
Bouamar
Rachida
R
van Gelder
Teun
T
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D065095:Calcineurin Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D014644:Genetic Variation; D006084:Graft Rejection / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000502:physiology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A