MECHANISM OF PROTEINURIA IN NON-GLOMERULAR RENAL-DISEASE

The present study was designed to investigate the mechanisms responsible for the proteinuria observed in nonglomerular renal disease. In rats with experimental unilateral pyelonephritis, protein excretion rates from the diseased and contralateral control kidneys were similar. Protein excretion from the pyelonephritic kidneys, however, increased five-fold after the control kidneys had been removed. Similar results were obtained in animals with surgically induced reduction of renal mass in one kidney. Unilateral nephrectomy of normal rats was associated with increased protein excretion in the urine from the remaining single kidney. Thus, the increased proteinuria did not result from any demonstrable anatomic abnormalities, nor was it the consequence of the biochemical changes seen in azotemia. No loss of glomerular polyanion could be demonstrated in the glomeruli of animals with reduced renal mass. Proteinuria could not be induced by increasing GFR per nephron, by an osmotic diuresis, or by saline infusion, even though the latter maneuvers induced marked natriuresis and presumably modified tubular function. The increased urinary protein excretion consisted not only of albumin but also of larger molecular-weight proteins with the electrophoretic characteristics of globulins. Moreover, glomerular permselectivity measured from the clearances of polydisperse polyvinyl pyrrolidone (PVP) in animals with a 50% or greater reduction in renal mass was markedly abnormal. The clearances of PVP molecules similar to or greater in size than albumin were increased significantly in excess of the concomitant increases in inulin clearance. We suggest that an alteration in glomerular permselectivity is an integral part of the adaptive changes which occur when nephron mass is reduced, that this change permits an increased passage of plasma proteins across the glomerular barrier, and that this results in the increased proteinuria observed from remaining nephrons when total renal mass is reduced.