Correlation between histologic features and glomerular permeability in membranous nephropathy and immunoglobulin A...

We evaluated the correlation between histologic features and glomerular permselectivity based on fractional clearances of dextrans relative to inulin (FCsDex). The subjects consisted of 12 healthy volunteers, 18 patients with membranous nephropathy, and 20 patients with immunoglobulin A nephropathy. In membranous nephropathy, FCsDex measured with large dextrans (radii larger than 56 A) increased as the capillary lesion progressed. Histologic examination showed that glomerular capillary alteration was the factor most closely linked to changes in FCsDex in membranous nephropathy. Proteinuria (normalized to glomerular filtration rate) did not correlate with FCsDex. Increased FCsDex tended to normalize during prednisolone treatment in membranous nephropathy. In immunoglobulin A nephropathy, the impairment of glomerular size selectivity depended on the degree of mesangial sclerosis and tubulointerstitial injury. FCs of dextrans of 59 A were correlated with the mesangial sclerosis index (r = 0.573, p = 0.050) and the tubulointerstitial injury index (r = 0.707, p = 0.003). Proteinuria (again normalized to glomerular filtration rate) was significantly correlated with FCs of large dextrans in immunoglobulin A nephropathy (r = 0.668, p = 0.008). We conclude that glomerular size-selective barriers were impaired both in membranous nephropathy and immunoglobulin A nephropathy. However, the mechanisms of impaired size selectivity might differ, at least in part, between these nephropathies. The predominant factors responsible for the size-selective defect seemed to be glomerular capillary wall lesions in membranous nephropathy but mesangial sclerosis or tubulointerstitial damages (or both) in immunoglobulin A nephropathy.