The evolution of membranous glomerulonephritis reconsidered: new insights from a study on relapsing disease

Membranous glomerulonephritis (MGN) has a highly variable clinical course. The morphological basis for this variability has not been fully elucidated. We studied 10 patients with relapsing MGN and compared the findings with those in other clinical courses. The mean duration of follow-up was 10.4 years. Clinical remission occurred, on average, 1.5 years and relapse, on average, 5.6 years after onset. Thirty-one renal biopsies obtained at various clinical phases were studied, 22 of them electron microscopically. The ultrastructural and clinical alterations paralleled each other closely. Subepithelial electron-dense deposits were present during the primary nephrotic phase, were replaced by intramembranous lucent deposits during remission, and reappeared again during relapse. Light microscopic changes (projections, thickening) of the glomerular capillary basement membrane (GBM) were variable. Both ultrastructural and light microscopic changes were unreliable indicators of the duration of illness. A comparative analysis of the present and previous findings suggests that the length of time during which new deposit material is formed determines the evolution of the membranous lesion and the corresponding clinical course. Thus, a short duration results in a single generation of deposits, a morphologically and clinically healing course, and no thickening of the GBM. A repeated formation of deposit material results in a new generation of subepithelial deposits, and a relapsing course. A prolonged formation results in a continuous presence of subepithelial deposits, a thickening of the GBM, and a protracted or progressive course. The morphologic staging currently in use pertains to one particular evolution and course of MGN and therefore should not be used.