Unilateral renal disease in the rat. I. Clinical, morphologic, and glomerular mesangial functional features of the experimental model produced by renal perfusion with aminonucleoside

Unilateral renal perfusion with the aminonucleoside of puromycin (60 mg. per kilogram) was used to produce unilateral renal disease in rats characterized by marked proteinuria, hypoalbuminemia, and hypercholesterolemia. Urine albumin excretion increased from 0.21 ± 0.16 mg. per 24 hours prior to perfusion to 126 ± 30 mg. on the fourteenth day after perfusion. If the perfused kidney was removed after 10 days, urine albumin excretion immediately decreased to normal, whereas marked proteinuria continued after contralateral nephrectomy. Immunofluorescent studies revealed abundant protein reabsorption droplets (β₁C and albumin) in proximal tubules of aminonucleoside-perfused kidneys but not in contralateral kidneys thus indicating that the increased proteinuria was of unilateral origin. Less marked proteinuria was observed following unilateral renal perfusion with lower doses of aminonucleoside. Glomerular mesangial function was studied 10 days after renal perfusion. Renal specimens were obtained 12 hours after intravenous injection of 37.5 mg. per 100 Gm. of body weight of aggregated human IgG and evaluated by immunofluorescent microscopy. Glomerular mesangial staining for human IgG in aminonucleoside-perfused kidneys was markedly increased when compared to contralateral kidneys. In contrast, mesangial staining in kidneys perfused with saline was equal to that of contralateral kidneys and proteinuria following perfusion with saline was not increased. These studies provide further evidence that increased proteinuria following administration of aminonucleoside to rats is the result of a rapid direct effect on the kidney and that alterations of glomerular mesangial function are related to renal factors rather than changes in systemic milieu.