MYOFIBROBLASTS, PREDICTORS OF PROGRESSION OF MESANGIAL IGA NEPHROPATHY

The limited knowledge of the cellular mediators of renal scarring hamp ers progress in the management of progressive chronic renal failure (C RF). We have studied 38 patients with biopsy-proven mesangial IgA neph ropathy with emphasis on attempting to define the role of myofibroblas ts (alpha-smooth muscle actin/SMA-positive cells) in renal scarring. I n 18 untreated patients, correlations were undertaken between known hi stological parameters of progression as well as the presence of myofib roblasts in tissues and the clinical outcome. alpha-SMA staining by an avidin-biotin-peroxidase method was confined to a large extent to the vascular smooth muscle cells of normal kidneys but extended to the tu bulointerstitium and periglomerular space in scarred kidneys. Mild glo merular staining was also noted. The interstitial immunostain followed a similar distribution to that of interstitial type III collagen. Mor phometric analysis showed the interstitial alpha-SMA staining to be a reliable histological predictor of outcome as it discriminated between progressors and non-progressors (chi2 = 4.923, P=0.026). The intensit y of the interstitial alpha-SMA staining correlated with renal functio nal outcome; inversely with the reciprocal of serum creatinine slopes (r=-0.466, P<0.025) and positively with the serum creatinine value at the end of the observation period (r=0.704, P<0.001). Other histologic al parameters that correlated with outcome included the degree of tubu lointerstitial (TI) inflammatory infiltrate (r=-0.425, P<0.05 with 1/C r slope and r=0.760, P<0.001 with serum creatinine) and the intensity of the TI staining for collagen IV (r=-0.567 and 0.667 respectively). In 20 patients treated with prednisolone and azathioprine, a second re nal biopsy showed the persistence of interstitial myofibroblasts in th e absence of progressive fibrosis. In conclusion, staining of renal bi opsies of patients with mesangial IgA for alpha-SMA-positive cells may identify the myofibroblasts as important mediators of TI scarring and have useful prognostic implications.