Prevention of posttransplant acute tubular necrosis by the calcium antagonist diltiazem: a prospective randomized study

Abstract

In a prospective randomized trial we evaluated the influence of the calcium antagonist diltiazem (Dil) on the development of acute tubular necrosis (ATN) in cadaveric kidney transplantation. Dil was added to Eurocollin's solution (20 mg/l) at donor nephrectomy. The graft recipient received a preoperative bolus injection of Dil (0.28 mg/kg) which was followed by an infusion of Dil (0.0022 mg/min/kg) for 2 days. Thereafter, Dil was applied orally. Immunosuppressive therapy consisted of ciclosporin (CS) and low-dose steroids. There were no significant differences between the groups with respect to donor characteristics, HLA matching and ischemic periods. In the control group (n = 22), 9 patients (41%) developed ATN compared to 2 patients (10%) in the Dil group (p less than 0.05). In the control group, 3.5 +/- 0.4 HD per patient were necessary compared to 0.6 +/- 0.2 in the Dil group (p less than 0.05). Although CS blood levels were significantly higher in the Dil group (1st week 1,150 vs. 728 ng/ml; p less than 0.01), the GFR of grafts with primary function was significantly higher in the Dil group (day 7:39 vs. 24 ml/min; p less than 0.05). A significant reduction of the CS dose by 30% (p less than 0.01) led to comparable CS levels. In the Dil group, significantly fewer rejection episodes occurred during the first month. Our data indicate that the application of the calcium antagonist Dil lowered the incidence of posttransplant ATN. In addition, there is a possibility that Dil not only ameliorates ischemic damage in the kidney, but also reduces CS nephrotoxicity.