A randomized, placebo-controlled trial of IGF-1 for delayed graft function: A human model to study postischemic ARF

Abstract

Background. Insulin-like growth factor (IGF-1) has been shown in animal models to accelerate recovery from acute renal failure (ARF). However, a therapeutic trial of recombinant human (rh) IGF-1 in patients with ARF in the intensive care unit (ICU) failed to demonstrate efficacy [1]. Such patients often had multiple organ failure, recurrent renal injury, and a delay of several days before commencing treatment. Methods. To circumvent these confounding factors, we randomized recipients of cadaveric renal allografts to immediate (<5 hours) rhIGF-1 versus placebo therapy (100 mg/kg subcutaneously twice a day for 6 days). Preliminary observations 3 hours posttransplantation in an additional 44 patients revealed a creatinine clearance ≤ 20 mL/min to predict protracted ARF. Thus, this value was used to determine study eligibility. Results. Creatinine clearance prior to commencing treatment was not significantly different between the two groups (8 ± 5 mL/min for IGF-1 and 7 ± 6 mL/min for placebo; P = 0.39). Inulin clearance on day 7, the primary outcome measure, was 21 ± 22 mL/min and 19 ± 19 mL/min in the IGF-1 (N = 19) and placebo (N = 24) groups, respectively (P = 0.67). Secondary outcome measures, including nadir serum creatinines after 6 weeks and need for dialysis, also did not differ between the two groups. We performed an analysis of statistical power using the placebo arm of the trial. Defining a twofold increase above placebo in day 7 glomerular filtration rate (GFR) as of meaningful biologic significance, we determined that the modest sample size used in the present study is adequate. Conclusion. We, thus, conclude that (1) IGF-1 treatment is unlikely to benefit ARF and (2) the transplanted kidney is a good model to screen new agents for ARF that have demonstrated promise in animal trials.