title: 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 < 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Medicine, Stanford University, Stanford, California, USA. michelle.hladunewich@sw.ca
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hladunewich
authors.forename: Geraldine
authors.initials: G
authors.lastname: Corrigan
authors.forename: Geraldine C
authors.initials: GC
authors.lastname: Derby
authors.forename: Deepa
authors.initials: D
authors.lastname: Ramaswamy
authors.forename: Neeraja
authors.initials: N
authors.lastname: Kambham
authors.forename: John D
authors.initials: JD
authors.lastname: Scandling
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Myers
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000188:drug therapy*; D000328:Adult; D003404:Creatinine / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D007511:Ischemia / Q000150:complications*; D016030:Kidney Transplantation; D008875:Middle Aged; D010919:Placebos; D011237:Predictive Value of Tests; D017211:Treatment Failure
chemical_list: D010919:Placebos; D007334:Insulin-Like Growth Factor I; D003404:Creatinine