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 plus or minus 0.16 mg. per 24 hours prior to perfusion to 126 plus or minus 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 (beta1C 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 on the kidney and that alterations of glomerular mesangial function are related to renal factors rather than changes in systemic milieu.