Potential causes and pathogenesis in autosomal dominant polycystic kidney disease.

To evaluate early pathological changes in autosomal dominant polycystic kidney disease (PKD), percutaneous renal biopsy specimens from 14 subjects at risk for PKD were analyzed. The subjects represented 5 unrelated families, ranged in age from 11 to 26 years and had normal excretory urograms. One additional renal tissue specimen was obtained at the time of nephrectomy from a patient with PKD and end-stage renal failure. In renal biopsy specimens from 5 subjects, light microscopy findings of dilated distal and collecting tubules suggested early manifestation of PKD. In 3 of these 5 subjects, PKD was documented 3 years later by repeated excretory urography. Polypoid and papillary hyperplasia of tubular epithelium was not seen in biopsy specimens but was present in the nephrectomy specimen. Electron microscopy revealed splitting of the lamina densa of the glomerular capillary basement in the nephrectomy specimen and in two biopsy specimens with light microscopic changes of tubular dilatation, from subjects with PKD documented 3 years later. In three biopsy specimens without light microscopic changes of tubular dilatation from subjects without PKD documented 3 years later and in the nephrectomy specimen, multilayering of the tubular basement membrane was seen on electron microscopy. These data indicate that structural abnormalities of the basement membranes may be the primary cause in cyst formation in autosomal dominant PKD. Evidence of tubular obstruction was not present.