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Recovery from AKI involves increased expression of various growth factors acting via autocrine, paracrine, and endocrine mechanisms. The advent of recombinant growth factors has stimulated research exploring their therapeutic potential in AKI. Experimental studies have yielded promising results with individual growth factors246 including insulin-like growth factor-1 (IGF-1), hepatic growth factor, and, more recently, erythropoietin. The physiological basis for the use of erythropoietin in the prevention of AKI has recently been described.247
IGF-1 is a peptide with renal vasodilatory, mitogenic and anabolic properties. rhIGF-1 has been demonstrated to accelerate the recovery of renal function in several animal models of AKI.248-251 Three double-blind, placebo-controlled RCTs have addressed the usefulness of IGF-1 in adults with imminent or established AKI.252-254 Franklin et al.,252 administered rhIGF-1 every 12 hours for 3 days postoperatively to 54 patients undergoing abdominal aortic surgery. While no patient developed ARF, a smaller proportion of IGF-1–treated patients showed a decline in GFR as compared to the placebo group (22% vs. 33%). Hladunewich et al.,254 administered rhIGF-1 or placebo in 43 patients undergoing cadaveric renal transplantation at high risk of delayed graft function. Treatment was started within 5 hours of transplantation and continued for 6 days. On day 7, neither inulin clearance, nor urine flow or fractional sodium excretion differed between the treatment arms, nor did the nadir SCr after 6 weeks or the proportion of patients require post-transplantation dialysis. Hirschberg et al.,253 treated 72 patients suffering from AKI mainly due to sepsis or hemodynamic shock with either rhIGF-1 or placebo for a mean of 10.6 days. No differences were observed with respect to changes in GFR, urine output, need for RRT, and mortality. Hence, despite its therapeutic efficacy in various animal models of ARF, rhIGF-1 largely failed to prevent or accelerate recovery from established AKI in humans. In addition, the high cost of this treatment should be mentioned.
Based on an analysis of the three RCTs with rhIGF-1 that are currently available and which were overall negative or at least equivocal, and considering that there is no benefit and the concern over potential harm and cost associated with this drug, the Work Group recommends against its use in patients with AKI.
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