INSULIN-LIKE GROWTH FACTOR-I AMELIORATES TRANSIENT ISCHEMIA-INDUCED ACUTE-RENAL-FAILURE IN RATS

Acute renal failure in rats was induced by transient occlusion of bila teral renal arteries and veins to investigate whether insulin-like gro wth factor-I (IGF-I) has an effect on the damaged renal function or no t. Administration of IGF-I at 0.01, 0.1 and 1 mg/kg by s.c. injection caused a 18.7, 33.0 and 66.5% increase of glomerular filtration rate a nd 54.8, 61.2 and 84.1 % decrease of blood urea nitrogen, respectively , compared with the values in the saline-treated group 2 days after is chemia. Other renal parameters tested such as fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and tubular reabsorptance of p hosphorus which are thought to represent renal function of proximal an d distal tubules, respectively, were also improved by IGF-I treatment. A histochemical study also supported these observations. Severe epith elial necrosis of proximal tubules and decrease of brush borders were observed 2 days after transient ischemia in the saline-treated group, whereas marked histochemical alterations were not observed in the IGF- I-treated group. L-N(G)-nitroarginine, an inhibitor of nitric oxide sy nthetase, prevented the improvement of glomerular filtration rate and blood urea nitrogen by IGF-I at 1 mg/kg, suggesting that the ameliorat ive action on renal function by IGF-I is mediated via nitric oxide, po ssibly its vasodilating action. These findings provide the first evide nce for the efficacy of IGF-I in the model of acute renal failure, sug gesting that IGF-I may be useful for the treatment of acute renal fail ure.