Alport's syndrome. Emphasizing electron microscopic studies of the glomerulus

Abstract

The pathogenesis of Alport's syndrome is not known; later histologic findings are controversial, and the site of early pathologic change in the kidney has been obscure. Ultrastructural studies of renal tissue from 8 affected patients revealed striking glomerular lesions, even in biopsies with few abnormalities by light microscopy. The most impressive lesions, present in all patients, were thickening of the basement membrane and splitting and splintering of the lamina densa, in a focal and local distribution. Flocculent basement membrane precipitate and extreme thinning of the lamina densa also occurred. Dense deposits were not seen. Focal-local sclerosis was frequently seen by light and electron microscopy. The cause of these lesions is unknown. Absence of dense deposits in glomeruli is consistent with previous immunofluorescent demonstrations of absent immunoglobulins. These studies suggest that glomerular basement membrane may be a site of early pathologic change in at least some patients with Alport's syndrome.