A randomized, placebo-controlled trial of IGF-1 for delayed graft function: A human model to study postischemic ARF
✍ Scribed by Hladunewich, Michelle A.; Corrigan, Geraldine; Derby, Geraldine C.; Ramaswamy, Deepa; Kambham, Neeraja; Scandling, John D.; Myers, Bryan D.
- Book ID
- 104474758
- Publisher
- Nature Publishing Group
- Year
- 2003
- Tongue
- English
- Weight
- 293 KB
- Volume
- 64
- Category
- Article
- ISSN
- 0085-2538
No coin nor oath required. For personal study only.
✦ Synopsis
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 < or = 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.