Nephronophthisis. A primary tubular basement membrane defect.

In order to characterize abnormalities in nephronophthisis, renal tissues from four patients were studied by light and electron microscopies and immunofluorescence using antibodies to laminin, type IV collagen, and tubular basement membranes (TBM). There were constant morphological alterations affecting TBM of all segments of the nephron, with or without cysts. These included extreme thinning and attenuation, layering, and thickening of these structures which ranged in size from 36 nm to 2000 nm. A combination of these features often affected the same TBM simultaneously, with abrupt transitions between different lesions. Although the ultrastructural TBM aberrations were observed in a wide variety of other chronic and acute renal disorders, they rarely occurred to the extent as in nephronophthisis or with abrupt transitions, both suggesting diagnostic significance. Laminin and type IV collagen were present in normal intensity and distribution, however, anti-TBM antibody staining was inconstantly reduced, perhaps signifying lack of a normal antigenic component in the TBM. These findings may well indicate the fundamental defect in nephronophthisis to be production of abnormal TBM, similar to the glomerular basement membrane lesions and consequences in Alport's syndrome.