Rapamycin prevents interstitial fibrosis in renal allografts through decreasing angiogenesis and inflammation
B H Özdemir1, A A Özdemir, R Erdal
1Department of Pathology, Başkent University, Ankara, Turkey. handan27@hotmail.com
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.
Insights
Rapamycin (RPM) reduces interstitial fibrosis (IF) and inflammation in kidney transplant recipients. RPM therapy improves long-term graft survival compared to cyclosporine.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Interstitial fibrosis (IF) is a major cause of graft loss.
- Rapamycin (RPM) exhibits antiangiogenic and antiproliferative properties.
- The antifibrotic potential of RPM in renal transplantation requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of Rapamycin (RPM) as an antifibrotic agent in renal transplant recipients.
- To assess the impact of RPM on interstitial fibrosis (IF) and graft survival.
- To elucidate the mechanisms underlying RPM's antifibrotic effects.
Main Methods:
- A comparative study of 60 renal transplant recipients divided into RPM (n=20) and cyclosporine (n=40) groups.
- Analysis of interstitial macrophages, lymphocytes, and microvessel density (MVD) using CD34 staining in biopsies.
- Evaluation of IF development and graft survival over 18 months and up to 5 years.
Main Results:
- RPM group showed significantly lower MVD, macrophage, and lymphocyte infiltration compared to the cyclosporine group (P<.001).
- Fewer RPM-treated patients developed IF (10% vs. 35%, P<.05).
- RPM therapy was associated with significantly higher 1-, 3-, and 5-year graft survival rates (95%, 95%, 89% vs. 95%, 65%, 45%, P<.001).
Conclusions:
- Rapamycin demonstrates significant antifibrotic effects in renal transplant recipients.
- RPM's antiproliferative and antiangiogenic mechanisms contribute to reduced interstitial fibrosis.
- RPM therapy offers a positive and independent impact on long-term renal graft survival.
