RECOVERY FROM ACUTE ISCHEMIC RENAL-FAILURE IS ACCELERATED BY DES(1-3)-INSULIN-LIKE GROWTH-FACTOR-I

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 ins ult and that hasten repair. Insulin-like growth factor-1 is mitogenic for renal tubular cells; in normal kidneys it bas haemodynamic effects and it is potently anabolic. We tested the theory that insulin-like g rowth factor-1 may be of use in the treatment of acute renal failure b y 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 minipum p for 7 days. The rats were weighed and bled daily and in one experime nt 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 d es-(1-3)-insulin-like growth factor-1 significantly increased creatini ne clearance and reduced fractional excretion of filtered sodium. Besi des these beneficial effects on kidney function, des-(1-3)-insulin-lik e growth factor-1 was anabolic as treated rats gained weight while con trol 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 f or the treatment of acute renal failure.