Hypertensinogenic mechanism of the calcineurin inhibitors.
Kidney transplantation has seen a remarkable improvement in allograft survival rates and patient survival rates, and an equally remarkable reduction in acute rejection rates. Most attribute these changes to the introduction and widespread use of calcineurin inhibitors as part of the standard immunosuppressive regimen. Cyclosporine and tacrolimus are ideal immunosuppressive agents, much more effective and safe than the previous agents used. Especially ironic, however, for those caring for kidney transplant patients has been the finding that these breakthrough agents are toxic to the kidney and can cause hypertension. We can protect the transplanted kidney from rejection, but still damage it paradoxically by the protecting agent. Moreover, the prevalence of hypertension in transplant clinics has increased (from 40%-50% to up to 90%-100%) as these newer agents have gained widespread use. We remain uncertain of the mechanism whereby these agents cause hypertension, and therefore remain uncertain of the ideal treatment; however, the search for a mechanism has taken us from the organ level to intracellular effects of the agents. The fact that both agents cause nephrotoxicity suggests that a renal mechanism is at the heart of the hypertension.
Curtis
John J
JJ
University of Alabama at Birmingham, Division of Nephrology, 35294-0006, USA. jcurtis@nrtc.uab.edu
D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications; D016030:Kidney Transplantation; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus