Alport's syndrome (progressive hereditary nephritis)

33 kidney biopsies from 29 patients, most of whom were under 20 years of age, were examined by light microscopy and 13 by electron microscopy. At the time of biopsy, the serum creatinine and blood pressure were normal in all patients. The creatinine clearance was slightly reduced in 10. Hematuria was seen in all and proteinuria in 23 subjects. Glomerular changes as observed with the light microscope varied from slight mesangial matrix and cell proliferation and focal thickening of the peripheral glomerular basement membrane (BM) to segmental glomerular lesions. In all patients studied by electron microscopy, thickening and irregularity of the external side of the glomerular capillary BM were seen, as well as a specific and characteristic lamellation or, more rarely, reticulation of the lamina densa. Between the strips of densa material, some granular or amorphous osmiophilic material and some membrane bound bodies could, on occasion, be identified. The BM changes advanced rapidly in males but were relatively static in females. The BM of Bowman's capsule and tubules showed only nonspecific thickening. The appearance of segmental glomerular lesions signaled the initiation of a rapidly progressive obliteration of glomeruli, which, in turn, led to interstitial changes (inflammation, fibrosis) terminating in a contracted kidney. Whether the primary lesion in Alport's syndrome is entirely limited to the glomerular basement membrane cannot yet be decided. Despite new insights into the morphogenesis of this peculiar syndrome the pathogenesis awaits elucidation.