Nature of progressive glomerulosclerosis in human membranous nephropathy

In membranous nephropathy (MN) the mechanism of progression is not well defined. We studied the lesions of focal segmental glomerulosclerosis (FSGS) in 95 patients with idiopathic MN in relation to other morphologic and clinical data. Forty-one patients (43%) showed FSGS, frequently accompanied by synechiae and hyalinosis. The patients with FSGS had a significantly greater degree of mesangial expansion, glomerular basement membrane (GBM) thickening, interstitial fibrosis, and arteriolosclerosis, as well as an increased level of serum creatinine, when compared to the patients without. Relative interstitial volume, in particular, significantly correlated to the serum creatinine level, thickness of GBM and % of glomeruli with FSGS. Glomerular size was not different in patients with or without FSGS. When clinical and morphological data of these patients were analyzed according to a staging technique of Ehrenreich and Churg [1968], the occurrence of FSGS was more frequently present in advanced stage. Intraglomerular fat deposition was only noted in advanced stage. No other morphologic or clinical parameters were related to the staging. Thickness of GBM or index of electron density of deposits, though well related to the morphological staging, did not show any relationship to clinical or laboratory data. Sixty-four patients were followed for more than a year (mean 3 years). Patients with FSGS had more frequent progression compared with those without. Patients with advanced stage and FSGS did not do worse than patients with stage I-II+II and FSGS. From these observations, we believe that the mesangial expansion, advanced GBM thickening, interstitial fibrosis and arteriolosclerosis are important morphological parameters, which may play a role in the genesis of FSGS or progression in MN. In addition, the occurrence of FSGS, but not the morphological staging, can predict the course of individual patients in MN.