Rationale For Insulinlike Growth Factor I Igfi In Acute Renal Failure

FIGURE 17-19

Reported therapeutic trials of insulin-like growth factor (IGF-I) in humans. Based on the compelling animal data and the fact that there are clearly identified disease states involving both over- and underexpression of IGF-I, this is the first growth factor that has been used in clinical trials for kidney disease. Listed above are a variety of studies of the effects of IGF-I in humans. This peptide has now been examined in several published studies of both acute and chronic renal failure. Additional studies are currently in progress.

In the area of acute renal failure there are now two reported trials of IGF-I. In the initial study IGF-I or placebo was administered to patients undergoing surgery involving the suprarenal aorta or the renal arteries. This group was selected as it best simulated the work that had been reported in animal trials of ischemic acute renal injury. Fifty-four patients were randomized in a double-blind, placebo-controlled trial of IGF-I to prevent the acute decline in renal function frequently associated with this type of surgery. The primary end-point in this study was the incidence of renal dysfunction, defined as a reduction of the glomerular filtration rate as compared with a preoperative baseline, at each of three measurements obtained during the 3 postoperative days. Modern surgical techniques have decreased the incidence of acute renal failure to such a low level, even in this high-risk group, so as to make it impractical to perform a single center trial with enough power to obtain differences in clinically important end-points. Thus, this trial was intended only to offer "proof of concept" that IGF-I is useful for patients with acute renal injuries.

Receptors are present on proximal tubules Regulates proximal tubule metabolism and transport

3530252015105 0

*P<0.05 Chi square

Placebo IGF-I

Treatment groups

Increases renal plasma flow and glomerular filtration rates Mitogenic for proximal tubule cells Enhanced expression after acute renal injury Anabolic

FIGURE 17-20

Incidence of postoperative renal dysfunction treated with insulin (IGF-I) or placebo. IGF-I significantly reduced the incidence of postoperative renal dysfunction in these high-risk patients. Renal dysfunction occurred in 33% of those who received placebo but in only 22% of patients treated with IGF-I. The groups were well-matched with respect to age, sex, type of operation, ischemia time, and baseline renal function as defined by serum creatinine or glomerular filtration rate. The IGF-I was tolerated well: no side effects were attributed to the drug. Secondary end-points such as discharge, serum creatinine, length of hospitalization, length of stay in the intensive care unit, or duration of intubation were not significantly different between the two groups. (Adapted from Franklin, et al. [3]; with permission.)

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