No difference in degree of interstitial Sirius red-stained area in serial biopsies from area under concentration-over-time curves-guided cyclosporine versus tacrolimus-treated renal transplant recipients at one year

J Am Soc Nephrol. 2006 Jan;17(1):305-12. doi: 10.1681/ASN.2005030249. Epub 2005 Nov 23.

Abstract

Interstitial fibrosis is the main characteristic of chronic allograft nephropathy and long-term graft failure. Cyclosporin (CsA) is thought to be more fibrogenic than tacrolimus. In a prospective, randomized, multicenter trial using a calcineurin-sparing regimen, renal interstitial volume was compared in CsA- and tacrolimus-treated renal transplant recipients by image analysis of Sirius red (SR)-stained cortical areas in protocol biopsies obtained at 6 mo (n = 94) and 12 mo (n = 97) after transplantation. Immunosuppression consisted of CsA or tacrolimus, CD25 mAb, mycophenolate mofetil, and prednisolone. CsA therapy increased the 6-mo risk for subclinical rejection. The prevalence of subclinical rejection was 38.8% in the CsA-treated and 15.2% in the tacrolimus-treated patient group (P = 0.012). Strikingly, no difference in the degree of interstitial SR-stained area was detectable between the two treatment groups. In particular, previous subclinical rejection episodes did not influence the degree of interstitial volume. Also, no difference in GFR occurred at 1 yr, when the mean GFR mounted 63 ml/min. No significant differences in the degree of interstitial SR-stained area could be observed at 6 and 12 mo between CsA- and tacrolimus-treated renal transplant recipients. Although CsA-treated patients developed significantly more subclinical rejections at 6 mo, this did not influence the degree of SR staining or the change in renal function at 1 yr.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Area Under Curve
  • Azo Compounds
  • Biopsy
  • Calcineurin Inhibitors*
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics
  • Cyclosporine / therapeutic use*
  • Fibrosis
  • Graft Rejection
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney / pathology*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / mortality
  • Prospective Studies
  • Staining and Labeling
  • Tacrolimus / administration & dosage
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use*

Substances

  • Azo Compounds
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • C.I. direct red 80
  • Cyclosporine
  • Tacrolimus