Insulin-Like Growth Factor Improves Renal Architecture of Fetal Kidneys with Complete Ureteral Obstruction

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Others have previously demonstrated that the administration of insulin-like growth factor-I accelerates recovery from ischemic acute tubular necrosis in the rat kidney. We investigated the effect of insulin-like growth factor-I on the histology of unilaterally obstructed kidneys in the pouch young of the North American opossum, Didelphis virginiana. In this model complete unilateral ureteral obstruction reliably induces statistically significant degrees of caliceal dilatation, tubular cystic change, and cortical and medullary fibrosis in kidneys examined 1 week after the creation of complete obstruction. Cortical and medullary inflammation is also increased after 1 week of obstruction in this model but not to a degree that is statistically different than control (sham operated) animals. We administered insulin-like growth factor-I to opossum pups with complete unilateral obstruction created at a length of 5 cm. (age 25 days, human equivalent 18 to 20 weeks). Insulin-like growth factor-I (400 mcg./kg.) was injected subcutaneously on the day of operation and again on days 2 and 4 postoperatively. The animals were sacrificed 1 week after obstruction and the formalin fixed, paraffin embedded kidneys were assessed histologically. In the obstructed kidney insulin-like growth factor-I ameliorated the development of fibrosis (cortical and medullary) and caliceal dilatation such that these characteristics did not differ significantly from those of sham operated animals. Tubular cystic change in the obstructed kidneys was also decreased by insulin-like growth factor-I administration but not to significant levels. Insulin-like growth factor-I treatment in obstructed animals resulted in significantly more inflammation (cortical and medullary) than in the sham operated animals. We also administered insulin-like growth factor-I to normal pups with no other intervention. These insulin-like growth factor-I treated pups did not differ from sham pups for any characteristic studied. Our study suggests that there is a protective effect of insulin-like growth factor-I on renal architecture when administered in the setting of experimental fetal ureteral obstruction.