Improvement of cadaver renal transplantation outcomes with verapamil: a review.
Although cyclosporin A (CsA) has allowed substantial advances in organ transplantation due to its immunosuppressive properties, its use is complicated by its direct nephrotoxic effects. Initial studies with mice confirmed that CsA caused a dose-related inhibition of the subcapsular microcirculation; subsequent clinical investigations have confirmed this inhibitory effect. Efforts to circumvent CsA-induced nephrotoxicity have focused on calcium antagonists. For example, when the calcium antagonist verapamil was administered before the initiation of CsA, renal blood flow was maintained. Verapamil therapy was also associated with significantly fewer rejection episodes (3 of 22; 14%) within 4 weeks of transplantation than CsA therapy alone (10 of 18; 56%). In a current study, verapamil 10 mg was injected into the renal artery during surgery, followed by 120 mg tid orally for 14 days. This regimen reduced delayed function incidents (the need for dialysis) during the first post-transplant week. Excluding nonfunctioning kidneys and technical failures, there were no graft losses secondary to rejection in patients treated with verapamil. The beneficial effects of verapamil therapy on transplant outcome may be related to its ability to protect cells from ischemia, the selective vasodilation of the efferent arteriole, elevated CsA blood levels, and inherent immunosuppressive properties.
Dawidson
I
I
University of Texas, Southwestern Medical Center, Department of Surgery, Dallas 75235-9031.
Rooth
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P
D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D003524:Cyclosporins / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology*; D010865:Pilot Projects; D016032:Randomized Controlled Trials as Topic; D012079:Renal Circulation / Q000187:drug effects; D014181:Transplantation Immunology; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D003524:Cyclosporins; D014700:Verapamil