Multicenter clinical trial of recombinant human insulin-like growth factorI in patients with acute renal failure

Background. Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Se veral studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism. Methods. Our objective was to determine whether injections of recombinant h uman IGF-I (rhIGF-I) would enhance the recovery of renal function and is sa fe in patients with ARF. The study was designed as a randomized, double-bli nd, placebo-controlled trial in intensive care units in 20 teaching hospita ls. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 pa tients) or placebo (37 patients). The most common causes of ARF in the rhIG F-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (+/- SD) APACHE II scores in the rhIGF-I and placebo-treated grou ps were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo gro ups, the mean (median) urine volume and urinary iothalamate clearances (glo merular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) m1/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not dif fer between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 mu g/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary endpoint was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency o f hemodialysis or ultrafiltration, and mortality rate. Results. During the treatment period, which averaged 10.7 +/- 4.1 and 10.6 +/- 4.5 days in the rhIGF-I and placebo groups, there were no differences i n the changes from baseline values of the glomerular filtration rate, creat inine clearance, daily urine volume, or serum urea nitrogen, creatinine, al bumin or transferrin. In patients who did not receive renal replacement the rapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placeb o-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-tr eated patients and 12 placebo-treated patients died during the 28 days afte r the onset of treatment. Conclusions. rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.