Recovery from Acute Ischaemic Renal Failure is Accelerated by Des-(1–3)-Insulin-Like Growth Factor-1

Abstract

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. 3. Thus des-(1–3)-insulin-like growth factor-1 accelerated recovery from acute ischaemic injury and may be useful for the treatment of acute renal failure.