Chronic glucocorticoid therapy amplifies glomerular injury in rats with renal ablation.
Functional and/or structural measurements were performed in eight groups of Munich-Wistar rats after five-sixths nephrectomy. Groups 1 and 5 received no therapy. Groups 2 and 6 received daily doses of methylprednisolone (MP). Groups 3 and 7 received MP plus the angiotensin I converting enzyme inhibitor (CEI), benzazepril. Groups 4 and 8 received CEI alone. Groups 1 through 4 underwent micropuncture study 2 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate due to glomerular capillary hyperperfusion and hypertension. Administration of MP in group 2 resulted in comparable systemic hypertension, with further elevation of the single nephron glomerular filtration rate due to even higher values for glomerular perfusion and hydraulic pressure. Concurrent treatment with CEI in groups 3 and 4 controlled systemic and glomerular hypertension despite equivalent renal ablation and, in group 3, comparable doses of MP. Groups 5 through 8 were followed for 12 wk. Untreated group 1 rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP in group 6 dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI (groups 7 and 8) afforded striking protection against disease progression. Thus, potent vasodilator glucocorticoids may amplify hemodynamically mediated glomerular injury, whereas control of systemic and glomerular hypertension prevents this undesirable consequence of chronic steroid therapy.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D006973:Hypertension / Q000209:etiology; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D008775:Methylprednisolone