title: 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.
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.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. t.rowshani@amc.uva.nl
authors.forename: Ajda T
authors.initials: AT
authors.lastname: Rowshani
authors.forename: Eduard M
authors.initials: EM
authors.lastname: Scholten
authors.forename: Frederike
authors.initials: F
authors.lastname: Bemelman
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Mirza
authors.initials: M
authors.lastname: Idu
authors.forename: Marian C
authors.initials: MC
authors.lastname: Roos-van Groningen
authors.forename: Marian C R
authors.initials: MC
authors.lastname: van Groningen
authors.forename: Janto S
authors.initials: JS
authors.lastname: Surachno
authors.forename: Marko J K
authors.initials: MJ
authors.lastname: Mallat
authors.forename: Leendert C
authors.initials: LC
authors.lastname: Paul
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.forename: Ineke
authors.initials: I
authors.lastname: ten Berge
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
mesh_terms: D019540:Area Under Curve; D001391:Azo Compounds; D001706:Biopsy; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005355:Fibrosis; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D011446:Prospective Studies; D013194:Staining and Labeling; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D001391:Azo Compounds; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C009798:C.I. direct red 80; D016572:Cyclosporine; D016559:Tacrolimus