Autosomal dominant polycystic kidney disease. Early diagnosis and consideration of pathogenesis

Renal function studies and excretory urograms were performed for 16 asymptomatic subjects at risk for polycystic kidney disease (PKD). The subjects represented five unrelated families, and ranged in age from 11 to 26 years. Fourteen subjects with normal excretory urograms underwent percutaneous renal biopsy. An additional renal biopsy specimen was obtained at the time of nephrectomy from a subject who had PKD. In four of the 14 subjects who had biopsies, PKD was documented about three years later by excretory urograms with nephrotomograms, renal radionuclide imaging, and gray-scale ultrasonography. Light-microscopic findings of dilated distal and collecting tubules suggested early manifestations of PKD in the renal biopsy specimens from five of the 14 subjects. In three of these five subjects, but also in one of nine subjects without light-microscopic changes of tubular dilatation, PKD was documented three years later. By electron microscopy, no differences in fine structural details were seen between specimens with and without tubular dilation observed by light microscopy, except for splitting of the lamina densa of the glomerular capillary basement membrane, which was present in only two specimens with light-microscopic changes of tubular dilation from subjects with PKD documented three years later, and in the nephrectomy specimen. Renal function studies were normal for 14 subjects, including four who had documented PKD. These data suggest that light-microscopic changes of tubular dilation (seen in five of the 14 specimens, including three from the four restudied subjects in whom PKD was documented three years later) and electon-microscopic changes of lamina densa splitting (seen only in two specimens with light-microscopic changes of tubular dilatation from subjects with PKD documented three years later and in the nephrectomy specimen), may be the earliest recognizable histologic changes in the carriers of the abnormal gene for PKD. However, because in the early stages of PKD these histologic changes may not be diffusely distributed, we do not advocate renal biopsy, but would suggest excretory urograms (with nephrotomograph), radionuclide imaging, or gray-scale ultrasonography as the initial diagnostic procedures.