INSULIN-LIKE GROWTH-FACTOR-I AMELIORATES DELAYED KIDNEY GRAFT FUNCTION AND THE ACUTE NEPHROTOXIC EFFECTS OF CYCLOSPORINE

Background. Delayed graft function (DGF) is a relatively common compli cation after cadaveric renal transplantation. The adverse effect of DG F on longterm graft survival has lead to intensive efforts to reduce i schemic graft injury. In this study we examined the effects of a new p rotective treatment based on insulin growth factor (IGF)-I. We evaluat ed the impact of the treatment on renal recovery and on the nephrotoxi city that is a common side effect of mainstream immunosuppressants. Be cause therapy with IGF-I or the analog des(1-3)IGF-I is effective in t reating experimental ischemic renal failure, these peptides may be use ful as perspective clinical treatments. Methods. We have addressed thr ee areas relating to the potential use of IGF-I and its analog des(1-3 )IGF-I. First, because of the immunogenic properties of IGF-I, we asse ssed the effect of des(1-3)IGF-I on the rejection of skin allografts i n Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DG F induced by a combination of warm and cold ischemia. Finally we teste d whether IGF-I protects against acute cyclosporine nephrotoxicity. Re sults. Des(1-3)IGF-I did not accelerate the rejection of the skin graf ts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperat ive values of creatinine and blood urea nitrogen were significantly be tter (P<0.05) in treated animals. IGF-I also ameliorated the nephrotox icity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05), Conclusions. In evaluating this study it should be recognized that the animal models studied, although widely used, diff er from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DG F, and they deserve further studies.