Randomized clinical trial of the effect of microemulsion cyclosporin and tacrolimus on renal allograft fibrosis

Br J Surg. 2003 Jun;90(6):680-6. doi: 10.1002/bjs.4134.


Background: The aim of this study was to compare the effect of Neoral cyclosporin- and tacrolimus-based therapy on the development of renal allograft fibrosis (chronic allograft nephropathy; CAN) in a prospective randomized trial.

Methods: A total of 102 patients undergoing renal transplantation were randomized to immunosuppression with either microemulsion cyclosporin (Neoral; 15 mg per kg per day adjusted to whole-blood trough concentrations of 200-300 ng/ml) or tacrolimus (0.2 mg per kg per day adjusted to whole-blood trough levels of 8-15 ng/ml) in conjunction with steroids, or at a lower dose (7 mg per kg per day and 0.1 mg per kg per day respectively) with the addition of azathioprine for non-heart-beating renal transplant recipients. Renal transplant interstitial fibrosis was quantified using computerized histomorphometric measurement of picrosirius red-stained 1-year protocol renal transplant biopsies. Levels of interstitial fibrosis were compared in relation to observed efficacy and toxicity profiles of the two drugs.

Results: There was a significant increase in allograft interstitial fibrosis in the patients treated with Neoral compared with those given tacrolimus. There was no significant difference in the demographic characteristics between the patient groups or in the incidence of acute rejection (Neoral 36 per cent versus tacrolimus 35 per cent) or steroid-resistant rejection (both 10 per cent) between the two drugs. There was a higher incidence of insulin resistance in the tacrolimus group (post-transplant diabetes mellitus, glucose tolerance testing) but this was not statistically significant. Neoral was associated with a significant increase in total cholesterol (P = 0.030) and low-density lipoprotein (P = 0.021) levels, which persisted throughout the study period.

Conclusion: Despite equivalent efficacy and pretransplantation risk factors for CAN, Neoral was associated with increased allograft fibrosis and significantly higher serum low-density lipoprotein cholesterol levels compared with tacrolimus.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Analysis of Variance
  • Aspirin / administration & dosage
  • Cyclosporine / administration & dosage*
  • Extracellular Matrix / metabolism
  • Female
  • Fibrosis / prevention & control
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Transplantation / pathology*
  • Male
  • Nifedipine / administration & dosage
  • Prednisolone / administration & dosage
  • Prospective Studies
  • Tacrolimus / administration & dosage*
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage


  • Immunosuppressive Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Cyclosporine
  • Prednisolone
  • Nifedipine
  • Aspirin
  • Tacrolimus