INSULIN-LIKE GROWTH-FACTOR-I (IGF-1) ENHANCES RECOVERY FROM HGCL2-INDUCED ACUTE-RENAL-FAILURE - THE EFFECTS ON RENAL IGF-1, IGF-1 RECEPTOR,AND IGF-BINDING PROTEIN-1 MESSENGER-RNA

Several growth factors have been found to play an important role in th e recovery from acute renal failure (ARF). The effect of the continuou s subcutaneous infusion of human recombinant insulin-like growth facto r(IGF)-1 (125 mu g daily by osmotic minipumps) in a rat model of mercu ric chloride (HgCl2)-induced ARF was examined. HgCl2 (4 mg/kg) induced ARF with a mortality that was unaffected by IGF-1. However, IGF-1 sig nificantly enhanced functional and histologic recovery in the survivor s, as measured by serum creatinine and creatinine clearance and by his tologic scoring. Solution hybridization RNAase protection assays showe d that renal IGF-1 mRNA, IGF-1 receptor (IGF-1R) mRNA, and IGF-binding protein-1 (IGFBP-1) mRNA were unaffected by exogenous IGF-1, but this treatment significantly increased renal IGF-1 in ARF rats compared wi th normal rats and ARF rats not receiving IGF-1. After ARF renal mRNA for IGF-1 was decreased, IGF-1R was unchanged and IGFBP-1 was increase d. Similar changes occurred in IGf-1-infused ARF rats. Thus, (1) IGF-1 enhances recovery from nephrotoxic ARF both functionally and histolog ically; (2) in nephrotoxic ARF, there is (a) a reduction in IGF-1 mRNA expression that is not prevented by IGF-1 infusion, and (b) an increa se in renal IGFBP-1 mRNA, This may allow a significant increase in ren al IGF-1 levels in IGF-1-infused ARF rats, despite the decrease in ren al IGF-1 mRNA, A local increase in renal IGFBP-1 and IGF-1 may explain the accelerated recovery from ATN in this model. It was concluded tha t HgCl2-induced ARF is amenable to improvement by IGF-1 infusion and t hat the increase in renal IGFBP-1 mRNA may be an important modulator i n the recovery of the kidney.