EXPRESSION OF CYTOSKELETAL PROTEINS DIFFERENTIATES BETWEEN PROGRESSORS AND NONPROGRESSORS IN TREATED IDIOPATHIC MEMBRANES NEPHROPATHY

Myofibroblasts play an important role in wound healing in a variety of tissue injuries. They have also been implicated in tissue fibrosis in cluding renal scarring. This study was aimed at defining their role in one of the commonest forms of nephrotic syndrome in adults, namely me mbranous nephropathy. We have studied 21 patients with biopsy proven i diopathic membranous nephropathy who were treated with glucocorticoids , attempting to define the role of myofibroblasts (alpha-smooth muscle actin-positive as well as vimentin-positive cells) in the progression of this form of nephropathy. There were 13 non-progressors (NP) and 8 progressors (P). The clinical, histological, and immunohistochemical characteristics of both groups were compared. Immunohistochemical stai ning for myofibroblasts cytoplasmic markers alpha-smooth muscle actin (alpha-SMA) and vimentin relied on an avidin-biotin-peroxidase method. The level of blood pressure, degree of proteinuria, severity of inter stitial infiltrate and interstitial fibrosis did not differentiate P f rom NP. However, vascular sclerosis was more severe in P compared to N P (p < 0.016) and its severity predicted the subsequent functional out come (slope of the 1/serum creatinine against time; r(2) = 0.618, p < 0.01). Mesangial alpha-SMA was significantly higher in P (31 +/- 18.6% ) than in NP (14.5 +/- 9.8%), p < 0.015. Interstitial alpha-SMA immuno stain was also higher in P but did not reach statistical significance. However, the number of interstitial myofibroblasts (alpha-SMA positiv e cells) closely predicted the subsequent rate of the progression of c hronic renal failure (r(2) = 0.919, p < 0.0001). Mesangial vimentin ex pression was not different between both groups. By contrast, interstit ial vimentin immunostain was higher in P (19.1 +/- 8.8%) compared to N P(7.9 +/- 5.6%), p < 0.002. These data suggest that the expression of mesangial and interstitial cytoskeletal proteins (alpha-SMA and viment in) may have useful prognostic implications as they appear to differen tiate between patients with membranous nephropathy who respond to immu nosuppression and those who continue to progress.