Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats.
Effects of hepatocyte growth factor (HGF) administration were examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered 20 micrograms HGF subcutaneously 30 min postischemia had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced insulin clearances measured on day 2 postocclusion, reduced mortality, and much less injury evident by examination of kidney histologies 7 days postinjury. The tubular regeneration that occurred postischemic injury was reflected by increased incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU incorporation compared with vehicle, indicating enhanced mitogenesis. The weight loss that occurs postischemic injury was not ameliorated by the dose of HGF we employed. We conclude that administration of HGF postischemic injury to rats stimulates the recovery of normal kidney function and the regeneration of proximal tubular epithelium.
Miller
S B
SB
George M. O'Brien Kidney and Urological Diseases Center, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Martin
D R
DR
Kissane
J
J
Hammerman
M R
MR
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007511:Ischemia / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects; D012079:Renal Circulation; D016019:Survival Analysis
D017228:Hepatocyte Growth Factor; D003404:Creatinine; D001973:Bromodeoxyuridine