Miller S B, Moulton M, O'Shea M, Hammerman M R
George M. O'Brien Kidney and Urological Diseases Center, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
Kidney Int. 1994 Jul;46(1):201-7. doi: 10.1038/ki.1994.260.
To determine whether insulin-like growth factor I (IGF-I) affects kidney function in patients with end-stage chronic renal failure, we administered recombinant human IGF-I (rhIGF-I) (100 micrograms/kg body wt subcutaneously twice daily) to nine individuals with baseline inulin clearances below 21 ml/min/1.73 m2. Four patients were treated for four days (short-term treatment) and five for periods between 13 and 27 days (long-term treatment). Administration of rhIGF-I increased inulin clearance, p-aminohippurate (PAH) clearance and the percent tubular reabsorption of filtered phosphate, and decreased plasma creatinine, blood urea nitrogen (BUN) and plasma phosphate during short-term administration. Kidney volume was unchanged in patients receiving the growth factor. rhIGF-I did not cause weight gain, proteinuria or hypoglycemia. Inulin clearance was not increased significantly above baseline after 13 or 20 days of IGF-I administration. PAH clearance remained elevated after 13 days, but not after 20 days of IGF-I. Levels of total circulating IGF-I were elevated above basal levels during the entire course of long-term IGF-I administration. In contrast, levels of circulating IGF binding protein 3 (IGFBP3) declined over time. Side effects related to IGF-I forced discontinuation of its use in two of five patients undergoing long-term treatment, and side-effects possibly related to IGF-I prompted discontinuation of its use in two others. We conclude that rhIGF-I can enhance glomerular filtration rate and renal plasma flow when administered short-term to humans with end-stage chronic renal renal failure. Further studies will be required to define its efficacy and usefulness long-term.
为了确定胰岛素样生长因子I（IGF-I）是否会影响终末期慢性肾衰竭患者的肾功能，我们对9名菊粉清除率基线低于21 ml/min/1.73 m²的个体皮下注射重组人IGF-I（rhIGF-I）（100微克/千克体重，每日两次）。4名患者接受了4天的治疗（短期治疗），5名患者接受了13至27天的治疗（长期治疗）。短期给药期间，rhIGF-I可提高菊粉清除率、对氨基马尿酸（PAH）清除率以及滤过磷酸盐的肾小管重吸收百分比，并降低血浆肌酐、血尿素氮（BUN）和血浆磷酸盐水平。接受生长因子治疗的患者肾脏体积未发生变化。rhIGF-I未导致体重增加、蛋白尿或低血糖。在给予IGF-I 13天或20天后，菊粉清除率未显著高于基线水平。给予IGF-I 13天后PAH清除率仍升高，但20天后未升高。在长期给予IGF-I的整个过程中，循环中总IGF-I水平高于基础水平。相反，循环中IGF结合蛋白3（IGFBP3）水平随时间下降。与IGF-I相关的副作用导致5名接受长期治疗的患者中有2人被迫停药，另外2人因可能与IGF-I相关的副作用而停药。我们得出结论，短期给予终末期慢性肾衰竭患者rhIGF-I可提高肾小球滤过率和肾血浆流量。需要进一步研究来确定其长期疗效和实用性。
