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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

Ajda T. Rowshani^*,, Eduard M. Scholten, Frederike Bemelman^*, Michael Eikmans, Mirza Idu^||, Marian C.R. van Groningen, Janto S. Surachno^*, Marko J.K. Mallat, Leendert C. Paul, Johan W. de Fijter, Ingeborg M. Bajema, Ineke ten Berge^*, and Sandrine Florquin^¶

Department of Internal Medicine, ^* Divisions of Nephrology and Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam; Department of Nephrology and Pathology, Leiden University Medical Center, Leiden; and Departments of ^|| Vascular Surgery and ^¶ Pathology, Academic Medical Center, Amsterdam, The Netherlands

Address correspondence to: Dr. Ajda T. Rowshani, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Phone: +31-20-5663365; Fax: +31-20-6914904; E-mail: t.rowshani{at}amc.uva.nl

Received for publication March 6, 2005. Accepted for publication October 5, 2005.

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.

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