Effect of nitrendipine on renal function in renal-transplant patients treated with cyclosporin: a randomised trial

Lancet. 1999 Oct 23;354(9188):1415-20. doi: 10.1016/S0140-6736(99)08421-4.

Abstract

Background: Calcium antagonists such as nitrendipine reduce the effects of cyclosporin on renal haemodynamics, however, their long-term efficacy has not been established. We did a randomised trial to investigate the effects of nitrendipine on renal function in renal-transplant patients treated with cyclosporin.

Methods: 253 renal-transplant patients were recruited: 52 normotensive patients (diastolic blood pressure <90 mm Hg) were assigned placebo and 57 nitrendipine 5 mg twice daily; 71 hypertensive patients (diastolic blood pressure >90 to <115 mm Hg) were assigned placebo and 73 nitrendipine 10 mg twice daily. Nitrendipine was increased to 20 mg twice daily if the target diastolic blood pressure (<90 mm Hg) was not achieved. The patients were seen once a month for 24 months; blood pressure and serum creatinine concentration were recorded at each visit. Analysis was by intention to treat.

Findings: 63 patients were withdrawn (35 nitrendipine, 28 placebo). The mean serum creatinine concentration at baseline was slightly higher in the nitrendipine group (146.7 micromol/L [SE 4.42]) than in the placebo group (137.0 micromol/L [3.54]. At the 24-month endpoint or at dropout, serum creatinine concentration was significantly higher in the 123 patients in the placebo group than the 130 patients in the nitrendipine group (160.8 [7.1] vs 148.5 [5.3], p for effect of treatment=0.025, analysis of covariance in a two-way classification; 95% CI for difference -1.77 to -22.98). At study entry, the blood pressures of the placebo and the nitrendipine groups were almost identical. At 24 months, blood pressure was higher in the normotensive patients given a placebo than in those patients given nitrendipine. By contrast, blood-pressure values were similar in those hypertensive patients given a placebo and those given nitrendipine at the end of treatment.

Interpretation: The calcium antagonist nitrendipine has no adverse effects on kidney function in renal-transplant patients with cyclosporin. The drug has a small but significant nephroprotective effect, that is independent of the drug's antihypertensive action.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Creatinine / blood
  • Cyclosporine / therapeutic use*
  • Double-Blind Method
  • Glomerular Filtration Rate / drug effects*
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Middle Aged
  • Nitrendipine / pharmacology
  • Nitrendipine / therapeutic use*
  • Statistics, Nonparametric

Substances

  • Calcium Channel Blockers
  • Immunosuppressive Agents
  • Cyclosporine
  • Nitrendipine
  • Creatinine