Hirschberg R, Kopple J, Lipsett P, Benjamin E, Minei J, Albertson T, Munger M, Metzler M, Zaloga G, Murray M, Lowry S, Conger J, McKeown W, O'shea M, Baughman R, Wood K, Haupt M, Kaiser R, Simms H, Warnock D, Summer W, Hintz R, Myers B, Haenftling K, Capra W
Harbor-UCLA Medical Center, Torrance, California, USA.
Kidney Int. 1999 Jun;55(6):2423-32. doi: 10.1046/j.1523-1755.1999.00463.x.
Patients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several 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.
Our objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-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 groups were 24 +/- 5 and 25 +/- 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 +/- 1037 (887) and 1402 +/- 1183 (1430) ml/24 hr and 6.4 +/- 5.9 (4.3) and 8.7 +/- 7.2 (4.4) ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12 hours with rhIGF-I, 100 microgram/kg desirable body weight, or placebo for up to 14 days. Injections were started within six days of the onset of ARF. The primary end-point 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 of hemodialysis or ultrafiltration, and mortality rate.
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 in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I-treated patients and 12 placebo-treated patients died during the 28 days after the onset of treatment.
rhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity.
急性肾衰竭（ARF）患者的发病率和死亡率很高，尤其是伴有严重合并症的患者。多项研究表明，在由缺血或某些肾毒素引起急性肾衰竭的大鼠中，胰岛素样生长因子-I（IGF-I）可促进肾功能恢复并抑制蛋白质分解代谢。
我们的目的是确定注射重组人生长因子-I（rhIGF-I）是否能促进急性肾衰竭患者肾功能的恢复以及是否安全。本研究设计为一项在20家教学医院重症监护病房进行的随机、双盲、安慰剂对照试验。72例急性肾衰竭患者被随机分为接受rhIGF-I治疗组（35例）和安慰剂组（37例）。rhIGF-I组和安慰剂组急性肾衰竭最常见的病因分别是脓毒症（分别占患者的37%和35%）以及低血压或血流动力学休克（分别占患者的42%和27%）。基线时，rhIGF-I治疗组和安慰剂治疗组的平均（±标准差）急性生理与慢性健康状况评分系统（APACHE II）分值分别为24±5和25±8。rhIGF-I组和安慰剂组的平均（中位数）尿量和碘肽酸盐清除率（肾小球滤过率）分别为1116±1037（887）和1402±1183（1430）ml/24小时以及6.4±5.9（4.3）和8.7±7.2（4.）ml/分钟，两组之间无差异。患者每12小时皮下注射一次rhIGF-I（100微克/千克理想体重）或安慰剂，持续14天。在急性肾衰竭发作后6天内开始注射。主要终点是肾小球滤过率相对于基线的变化。其他终点包括尿量、肌酐清除率、血清尿素、肌酐、白蛋白和转铁蛋白相对于基线的变化、血液透析或超滤的频率以及死亡率。
在治疗期间，rhIGF-I组和安慰剂组的平均时长分别为10.7±4.1天和10.6±4.5天，肾小球滤过率、肌酐清除率、每日尿量或血清尿素氮、肌酐、白蛋白或转铁蛋白相对于基线值的变化无差异。在未接受肾脏替代治疗的患者中，两组之间血清肌酐和尿素也无显著差异。rhIGF-I组的20例患者和安慰剂治疗组的17例患者接受了透析或超滤。12例接受rhIGF-I治疗的患者和12例接受安慰剂治疗的患者在治疗开始后的28天内死亡。
rhIGF-I并不能加速伴有大量合并症的急性肾衰竭患者肾功能的恢复。
