Fluvastatin in the prevention of renal transplant vasculopathy: results of a prospective, randomized, double-blind, placebo-controlled trial

Transplantation. 2008 Jul 15;86(1):82-7. doi: 10.1097/TP.0b013e318174428d.

Abstract

Background: Statins prevent the progression of transplant vasculopathy in heart transplants, but its beneficial effect on the transplanted kidney is controversial.

Methods: The aim is to evaluate the utility of fluvastatin 80 mg/day to reduce the progression of 6-month renal transplant vasculopathy in a multicenter, prospective, randomized, placebo-controlled trial stratified according to donor age. All patients received cyclosporine, mycophenolate mofetil, and prednisone. The progression of transplant vasculopathy was evaluated in paired donor and 6-month protocol biopsies. The primary efficacy variable was the progression of mean arterial intimal volume fraction (deltaVvintima/artery) evaluated with histomorphometry. The minimum sample size to detect a 50% reduction in the progression of deltaVvintima/artery was 62 patients per group. The secondary efficacy variable included the incidence of transplant vasculopathy evaluated according to Banff criteria.

Results: A total of 89 patients were included, 74 completed the 6-month study and 57 have paired biopsies with sufficient tissue for histological evaluation. The deltaVvintima/artery was not different between treatment and placebo groups (6.9+/-8.2% vs. 6.9+/-7.4%, P=ns), whereas the incidence of transplant vasculopathy was lower in the fluvastatin group (7% vs. 33%; P=0.02). Because there was a discrepancy between the primary and secondary efficacy variables, post hoc analysis was performed to evaluate the reproducibility of both variables in a subset of 50 biopsies. The reproducibility of transplant vasculopathy was higher than the reproducibility of Vvintima/artery (kappa 0.86 vs. 0.33).

Conclusions: In summary, there were no differences in deltaVvintima/artery between groups, but fluvastatin treatment was associated with a reduced incidence of transplant vasculopathy.

Publication types

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

MeSH terms

  • Adult
  • Belgium
  • Biopsy, Needle
  • Disease Progression
  • Double-Blind Method
  • Fatty Acids, Monounsaturated / adverse effects
  • Fatty Acids, Monounsaturated / therapeutic use*
  • Female
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Immunosuppressive Agents / therapeutic use
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Kidney / blood supply
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney / surgery
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Artery / drug effects
  • Renal Artery / pathology
  • Reproducibility of Results
  • Spain
  • Treatment Outcome
  • Tunica Intima / drug effects
  • Tunica Intima / pathology
  • Vascular Diseases / etiology
  • Vascular Diseases / pathology
  • Vascular Diseases / prevention & control*

Substances

  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunosuppressive Agents
  • Indoles
  • Fluvastatin