Expression of cytoskeletal proteins differentiates between progressors and non-progressors in treated idiopathic...

Myofibroblasts play an important role in wound healing in a variety of tissue injuries. They have also been implicated in tissue fibrosis including renal scarring. This study was aimed at defining their role in one of the commonest forms of nephrotic syndrome in adults, namely membranous nephropathy. We have studied 21 patients with biopsy proven idiopathic 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 staining for myofibroblasts cytoplasmic markers a-smooth muscle actin (alpha-SMA) and vimentin relied on an avidin-biotin-peroxidase method. The level of blood pressure, degree of proteinuria, severity of interstitial infiltrate and interstitial fibrosis did not differentiate P from NP. However, vascular sclerosis was more severe in P compared to NP (p < 0.016) and its severity predicted the subsequent functional outcome (slope of the 1/serum creatinine against time; r2 = 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 immunostain was also higher in P but did not reach statistical significance. However, the number of interstitial myofibroblasts (alpha-SMA positive cells) closely predicted the subsequent rate of the progression of chronic renal failure (r2 = 0.919, p < 0.0001). Mesangial vimentin expression was not different between both groups. By contrast, interstitial vimentin immunostain was higher in P (19.1 +/- 8.8%) compared to NP (7.9+/-5.6 %), p < 0.002. These data suggest that the expression of mesangial and interstitial cytoskeletal proteins (alpha-SMA and vimentin) may have useful prognostic implications as they appear to differentiate between patients with membranous nephropathy who respond to immunosuppression and those who continue to progress.