Protective effects of calcium antagonists in human renal transplantation.

Neumayer, Hans-Hellmut; Kunzendorf, Ulrich; Schreiber, Matthias

To test the hypothesis that calcium antagonists decrease the incidence and severity of delayed graft function, we conducted three separate, prospective, randomized trials. In these trials, we investi- gated the effects, of diltiazem and those of the prostacyclin analogue iloprost. In the first study, 22 control patients and 20 diltiazem patients received grafts perfumed with either vehicle or diltiazem 20 mg/liter in the Euro-Collins solution. Subsequently, the diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous infusion of 0.002 mg/min/kg for the following two days. Thereafter, diltiazem 60 mg was given to the treated subjects orally for up to four years. In the second study, II control subjects and 10 diltiazem subjects received the same postoperative regimen, but all grafts were harvested without addition of diltiazem to the perfusion solution. In the third protocol, four groups were studied as follows: 19 control subjects who received no specific treatment, 16 subjects who received diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both iloprost and diltiazem. The donor kidney of treated patients was perfused with either diltiazem, iloprost, or both drugs. Primary graft function occurred more commonly in the groups receiving diltiazem. Further, in the first study the number of hemodialyses per patient was reduced in those patients with delayed graft function. Fewer rejection episodes occurred in patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors decreased significantly during diltiazem treatment. Moreover, renal biopsies showed less severe signs of Cyclosporin A (CsA) nephrotoxicity in diltiazem-treated patients com- pared to controls, even though these patients also exhibited higher CsA trough levels. In the third study, the decrease in serum creatinine levels was more rapid in patients receiving diltiazem, with or without iloprost. After one year follow-up in this study, patients with primary graft function had lower creatinine values than those with delayed graft function. The long-term follow up of diltiazem-treated patients in the first two studies showed significantly lower serum creatinine levels at two years and a tendency of an improved graft survival up to four years (80% vs. 70%) compared to patients not given diltiazem. We conclude that diltiazem may blunt ischemic graft failure, and may be of value in preventing acute and chronic CsA nephrotoxicity.

KIDNEY transplantation; TRANSPLANTATION of organs, tissues, etc.; CALCIUM antagonists; CARDIOVASCULAR agents; DRUGS

Kidney International Supplement, 1992, Issue 36, pS-87

0098-6577

Academic Journal

10.1111/1523-1755.ep15066623