title: Rapamycin prevents interstitial fibrosis in renal allografts through decreasing angiogenesis and inflammation.
abstract: Rapamycin (RPM) has antiangiogenic and antiproliferative effects on cells. The aim of this study was to evaluate the mechanism of RPM as a novel antifibrotic agent by assessing its effect on interstitial fibrosis (IF). Among 60 renal transplant recipients, group 1 patients (n=20) were treated with RPM and group 2 (n=40), with cyclosporine. The proportions of infiltrating macrophages and lymphocytes in the interstitium were evaluated in 1-year biopsies. The microvessels were highlightened with CD34. After an initial biopsy, the development of diffuse IF over 18 months was evaluated by follow-up biopsies. The mean microvessel density (MVD) was significantly lower among group 1 (69.3±16) versus group 2 (96.5±30; P<.001). The proportions of macrophages and lymphocytes were lower in group 1 compared to group 2 biopsies (P<.001 for both). Fourteen (35%) group 2 and only 2 (10%) group 1 cases developed IF over 18 months (P<.05). The mean MVD in the initial biopsy was 75.6±18 in cases that did not versus 120±28 among those who did develop IF (P<.001). The amount of interstitial inflammation was greater among patients who did compared with cases who did not develop IF (P<.01). The overall 1-, 3-, and 5-year graft survival rates for group 1 were 95%, 95%, and 89% versus 95%, 65%, and 45% for group 2 patients, respectively (P<.001). RPM-treated patients showed a lower incidence of diffuse IF, which can be explained by antiproliferative and antiangiogenic effects of RPM. In conclusion, RPM therapy displayed an independently positive impact on long-term graft survival.
authors: Department of Pathology, Başkent University, Ankara, Turkey. handan27@hotmail.com
authors: B H
authors: BH
authors: Özdemir
authors: A A
authors: AA
authors: Özdemir
authors: R
authors: R
authors: Erdal
authors: F N
authors: FN
authors: Özdemir
authors: M
authors: M
authors: Haberal
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis; D001706:Biopsy; D049109:Cell Proliferation; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005355:Fibrosis / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation; D016030:Kidney Transplantation / Q000379:methods*; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D020123:Sirolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous / Q000379:methods*
chemical_list: D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus