The renal functional and structural consequences of corticosteroid and angiotensin-converting enzyme inhibitor therapy in chronic puromycin aminonucleoside nephropathy.
Glomerular diseases are characterized by increased urinary protein excretion. Treatment of this abnormality frequently involves administration of corticosteroids and angiotensin-converting enzyme inhibitors. There has been much recent interest in the potential impact of these drugs on progressive renal dysfunction, since they have opposing effects on intraglomerular hemodynamics. Therefore, we investigated the effect of methylprednisolone or captopril treatment on animals with chronic puromycin aminonucleoside nephropathy. In rats given a single injection of puromycin aminonucleoside, 15 mg/100 g body weight, both methylprednisolone and captopril significantly reduced proteinuria at 6 months [83 +/- 14 untreated (n = 7), 34 +/- 6 with methylprednisolone (n = 8), and 6 +/- 1 mg/24 h with captopril (n = 5), P less than 0.001]. Segmental glomerulosclerosis occurred with equal frequency in the untreated (7.8 +/- 2.3%) and methylprednisolone-treated rats (5.0 +/- 1.11%), but was significantly reduced by the administration of captopril (1.0 +/- 0.5%, P less than 0.001). We conclude that in chronic puromycin aminonucleoside nephropathy, treatment with corticosteroids reduces proteinuria without increasing the incidence of segmental glomerulosclerosis. Therapy with an angiotensin-converting enzyme inhibitor substantially decreases proteinuria and lessens the severity of glomerular scarring.
Trachtman
H
H
Department of Pediatrics (Division of Nephrology), Schneider Children'sHospital, Albert Einstein College of Medicine, New Hyde Park, NY 11042.
Del Pizzo
R
R
Valderrama
E
E
Gauthier
B
B
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology; D011692:Puromycin Aminonucleoside; D051381:Rats; D011919:Rats, Inbred Strains
D000305:Adrenal Cortex Hormones; D000806:Angiotensin-Converting Enzyme Inhibitors; D011692:Puromycin Aminonucleoside; D002216:Captopril; D008775:Methylprednisolone