Expression profile of mammalian target of rapamycin-related proteins in graft biopsy specimens: Significance for predicting interstitial fibrosis after kidney transplantation.

OBJECTIVE: To investigate the influence of the expression profile of mammalian target of rapamycin-related proteins on the development of interstitial fibrosis after kidney transplantation.

METHODS: Immunohistochemical staining was carried out to evaluate the expression of five mammalian target of rapamycin-related proteins (phosphorylated-Akt, Ras homolog enriched in brain, phosphorylated-mammalian target of rapamycin, phosphorylated-p70 ribosomal S6 kinase and phosphorylated-4E binding protein 1) in graft biopsy specimens obtained from 77 patients at 3 months after kidney transplantation. The change of the estimated glomerular filtration rate and the change of the fibrosis index (defined as the change in the percent area of fibrosis on Masson's trichrome-stained sections of biopsy specimens) from 3 months to 3 years after kidney transplantation were determined.

RESULTS: There was a significant correlation between change of the estimated glomerular filtration and change of the fibrosis index in the 77 patients. Univariate analysis identified expression of phosphorylated-Akt, phosphorylated-mammalian target of rapamycin and phosphorylated-p70 ribosomal S6 kinase, as well as donor type and pre-transplant dialysis duration, as significant predictors of a change of the fibrosis index >10%. However, only phosphorylated-mammalian target of rapamycin expression, phosphorylated-p70 ribosomal S6 kinase expression and donor type were independently associated with a change of the fibrosis index >10% according to multivariate analysis.

CONCLUSIONS: These findings suggest that mammalian target of rapamycin-related proteins are involved in the development of interstitial fibrosis after kidney transplantation.