PMC5437997_01
Kidney biopsy findings of membranous nephropathy and time course of disease. A: Light microscopy reveals glomeruli that are enlarged, with normal cellularity, and without signs of inflammation, fibrinoid necrosis, or sclerosis. The peripheral capillary walls reveal thickened basement membranes with spike-like projections on the silver-methenamine stain (not illustrated). There is no evidence of significant interstitial inflammation or fibrosis (PAS stain). B: Direct immunofluorescence microscopy reveals diffuse fine-granular deposition of IgG (illustrated) and less intense C3 and C1q staining (not illustrated) predominantly along the peripheral capillary walls. There is no reactivity for the PLA2R in these deposits (not illustrated). C: The electron micrograph shows a greatly distorted capillary wall, with numerous subepithelial electron-dense deposits (asterisks). Individual deposits are sometimes separated from each other by short basement membrane "spikes". The electron dense deposits are finely granular, but they do not show organized substructures. There is extensive effacement of the visceral epithelial cell foot processes. There are also several subendothelial deposits present (arrows). D: Time course of proteinuria in relation to the tapering of the sargramostim dose. Hatched line indicates urine albumin-to-creatinine ratio (g/g), and shaded area indicates the weekly dose of sargramostim.
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Figure1
Kidney biopsy revealed an immune complex-mediated glomerulopathy, with a diffuse membranous pattern of injury, characterized by numerous subepithelial electron-dense deposits, frequent subendothelial and mesangial electron-dense deposits, and strong reactivity of the deposits for IgG, C3, and C1q, most suggestive of a secondary membranous nephropathy (Figure 1A-C). In addition, considering that the membranous nephropathy might have been triggered not by PAP itself but by its treatment, the dose of sargramostim was progressively tapered off in close collaboration with the pulmonologist over the course of 1 year, which coincided with the full remission of the nephrotic syndrome (Figure 1D) and no clinical relapse of the PAP.