Calcium channel blockers in organ transplantation: important new therapeutic modalities

Abstract

The calcium channel blockers have emerged as important therapeutic modalities in the treatment of hypertension, ischemic heart disease, and other cardiovascular diseases. More recently, their potential benefit in recipients of organ transplants has come under closer scrutiny. Calcium channel blockers depress in vitro cellular immunity in an additive fashion with cyclosporine and have been demonstrated to reduce the incidence of rejection posttransplantation in early clinical trials. This class of drugs may also diminish ischemic damage to transplanted organs and reduce the destructive aspects of reperfusion injury. Because of their ability to depress cellular immune responses to mitogens, calcium channel blockers may also prove useful in decreasing the incidence of first-dose side effects (related to lymphocyte stimulation) in response to treatment with the OKT3 monoclonal antibody, a commonly used antirejection medication. Recent investigative efforts also suggest that calcium channel blockers may minimize cyclosporine nephrotoxicity by antagonizing either the direct or indirect vasoconstrictive actions of the drug. Some of the calcium channel blockers also reduce cyclosporine metabolism and excretion, thus allowing adequate levels of cyclosporine in blood with reduced doses of this valuable immunosuppressive agent. Cyclosporine-treated renal transplant recipients are frequently hypertensive, which is likely related to a salt-sensitive physiology. Calcium channel blockers have demonstrated important efficacy in reducing blood pressure in low-renin, salt-sensitive patients and similarly have been efficacious in controlling blood pressure in cyclosporine-treated transplant recipients. The numerous potential applications of calcium channel blockers in the field of organ transplantation illustrates the need for expanded clinical trials evaluating their use in this area.