Insulin-like growth factor 1 and endotoxin-mediated kidney dysfunction in critically ill, parenterally fed rats

Endotoxemia is an important contributor to the pathogenesis of acute kidney failure in sepsis. Data suggest insulin-like growth factor 1 (IGF-1) can increase creatinine clearance in healthy humans. The influence of recombinant human IGF-1 on kidney function in endotoxemia was investigated in 34 male Sprague-Dawley rats. After venous cannulation and postoperative parenteral nutrition (PN), the animals were randomly assigned to receive PN only, PN plus Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus IGF-1. Urine output was significantly higher for the IGF-1 and control groups compared with the LPS group (18.9 +/- 5.7, 13.0 +/- 3.8, and 17.7 +/- 3.1 ml/day for control, LPS, and IGF-1 groups, respectively, analysis of variance, p < 0.05). Creatinine clearance was significantly higher in the IGF-1 group than the LPS group and exceeded the control group (0.49 +/- 0.27, 0.36 +/- 0.14, and 0.65 +/- 0.27 ml.min-1.100(-1) g body wt) for control, LPS, and IGF-1, respectively (analysis of variance, p < 0.05). IGF-1 ameliorates the effects of endotoxin on kidney function as measured by creatinine clearance and urine output in endotoxemic parenterally fed rats.