Dense intramembranous deposit disease: new pathologic features

Abstract

The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tubulointerstitial nephritis, and two had focal segmental mesangial proliferative glomerulonephritis. The patients with membranoproliferative glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis had easily recognizable dense intramembranous deposits by optical microscopy. The patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis did not have recognizable peripheral loop dense intramembranous deposits even under oil immersion. In patients with membranoproliferative glomerulonephritis ultrastructural examination revealed extensive capillary wall dense intramembranous deposits. Immunofluorescence revealed diffuse double linear staining along the capillary walls and "mesangial rings" of C3. In the patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis the immunofluorescence study suggested a diagnosis of dense intramembranous deposit disease because of the segmental double linear staining of the capillary walls and "mesangial rings" of C3, but the diagnosis was only established by fine structural analysis where occasional peripheral loop and prominent paramesangial basement membrane dense intramembranous deposits and mesangial nodular deposits were identified. Clinical features prior to biopsy included nephrotic syndrome in eight patients, an acute nephritic syndrome in six patients, and asymptomatic proteinuria and hematuria in two patients. Five of six patients with an acute nephritic presentation had focal segmental necrotizing glomerulonephritis. The acute renal insufficiency in these patients was transitory and appeared to be related to a prominent acute tubulointerstitial nephritis present in four of the biopsy specimens. Depressed serum C3 levels were present in patients with membranoproliferative glomerulonephritis; patients with focal segmental lesions were normocomplementemic. Because of the "atypical" light microscopic features in six of our patients, we support the suggestion that membranoproliferative glomerulonephritis, type II be replaced by the term 'dense intramembranous deposit disease' for this glomerulopathy with variable clinical and histologic features.