Recovery from acute ischaemic renal failure is accelerated by des-(1-3)-insulin-like growth factor-1.
1. Acute renal failure carries a high risk of morbidity and mortality, so there is a need for agents that minimize renal injury after an insult and that hasten repair. Insulin-like growth factor-1 is mitogenic for renal tubular cells; in normal kidneys it has haemodynamic effects and it is potently anabolic. We tested the theory that insulin-like growth factor-1 may be of use in the treatment of acute renal failure by administering recombinant des-(1-3)-insulin-like growth factor-1, a truncated form of insulin-like growth factor-1, which occurs naturally. Ischaemic renal failure was induced in normal rats by occluding both renal pedicles for 60 min. Then des-(1-3)-insulin-like growth factor-1 (0.8 mg day-1 kg-1) or vehicle was given by subcutaneous minipump for 7 days. The rats were weighed and bled daily and in one experiment were housed in metabolic cages and urine was collected. 2. Des-(1-3)-insulin-like growth factor-1 caused a lower and earlier peak in both serum creatinine and blood urea-nitrogen levels, and a more rapid and complete return toward basal values than in untreated animals. Also des-(1-3)-insulin-like growth factor-1 significantly increased creatinine clearance and reduced fractional excretion of filtered sodium. Besides these beneficial effects on kidney function, des-(1-3)-insulin-like growth factor-1 was anabolic as treated rats gained weight while control rats lost weight. The mortality in control rats was 28% compared with 6% in treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Clark
R
R
Department of Endocrine Research, Genentech, Inc., San Francisco, California.
Mortensen
D
D
Rabkin
R
R
D058186:Acute Kidney Injury / Q000097:blood / Q000628:therapy*; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D007511:Ischemia / Q000097:blood / Q000628:therapy*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D010446:Peptide Fragments / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000187:drug effects
D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D003404:Creatinine