Glucocorticoids amplify glomerular injury in rats with renal ablation.
Male Munich-Wistar rats were subjected to 1 2/3 nephrectomy. One group received no therapy (C). A second group received daily doses of methylprednisolone (MP). A third group received MP plus the angiotensin I converting enzyme inhibitor (CEI) benzazepril. A fourth group received CEI alone. Half of the rats in each group underwent micropuncture study 2 weeks after ablation. Untreated rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR), due to glomerular capillary hyperperfusion and hypertension. Administration of MP resulted in comparable systemic hypertension with further elevation of SNGFR due to even higher values for glomerular perfusion and hydraulic pressure (PGC). Concurrent treatment with CEI-controlled systemic and glomerular hypertension despite equivalent renal ablation and comparable doses of MP. After 12 weeks untreated rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI 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.
García
D L
DL
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Rennke
H G
HG
Brenner
B M
BM
Anderson
S
S
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D000818:Animals; D001552:Benzazepines / Q000009:adverse effects; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000009:adverse effects; D006977:Hypertension, Renal / Q000139:chemically induced / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D009392:Nephrectomy; D009399:Nephrons / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D005938:Glucocorticoids; C044946:benazepril; D008775:Methylprednisolone