Rabkin R, Fervenza F C, Maidment H, Ike J, Hintz R, Liu F, Bloedow D C, Hoffman A R, Gesundheit N
Department of Medicine and Pediatrics, Stanford University School of Medicine, California, USA.
Kidney Int. 1996 Apr;49(4):1134-40. doi: 10.1038/ki.1996.164.
Information regarding the impact of chronic renal failure (CRF) on IGF-1 serum clearance is limited. Thus we evaluated the pharmacokinetics of insulin-like growth factor-1 (IGF-1) in six normal adults and six adults with advanced CRF (serum creatinine 7 +/- 0.8 mg/dl). All subjects were given 80 micrograms/kg recombinant human IGF-1 s.c. and blood was sampled over 48 hours. Baseline total serum IGF-1 levels were similar in both groups, but peak levels were elevated significantly in CRF; this was apparently related to the reduced distribution volume in CRF subjects. CRF did not affect the metabolic clearance rate (MCR) of total serum IGF-1. Immunoreactive IGF binding protein-3 (IGFBP-3) levels were greater in CRF. Western immunoblots revealed that the apparent increase in IGFBP-3 was largely due to an increase in immunoreactive fragments. IGFBP-3 protease activity was not increased. Thus IGFBP fragment accumulation likely reflects reduced fragment clearance. Western ligand blots revealed elevated 30 and 34 kDa IGFBP levels and IGFBP products in CRF serum. Serum acid labile subunit levels were unchanged in CRF. Peak free IGF-1 levels and the MCR of free IGF-1 did not differ between groups. In both groups the MCR of free IGF-1 exceeded the MCR of total IGF-1 by approximately 30-fold. These data suggest that in CRF patients receiving s.c. IGF-1: (a) total serum IGF-1 levels are increased as a result of elevated circulating IGFBPs that may restrict the distribution of IGF-1 beyond plasma; (b) serum free IGF-1 levels are not altered; and (c) the IGF-1 MCR is unchanged in CRF. Thus, in advanced CRF, apart from a reduction in the total IGF-1 volume of distribution the pharmacokinetics of IGF-1 are largely unaltered.
关于慢性肾衰竭（CRF）对胰岛素样生长因子-1（IGF-1）血清清除率影响的信息有限。因此，我们评估了6名正常成年人和6名晚期CRF成年人（血清肌酐7±0.8mg/dl）中胰岛素样生长因子-1（IGF-1）的药代动力学。所有受试者均皮下注射80μg/kg重组人IGF-1，并在48小时内采集血样。两组的基线血清总IGF-1水平相似，但CRF组的峰值水平显著升高；这显然与CRF受试者分布容积减少有关。CRF不影响血清总IGF-1的代谢清除率（MCR）。CRF患者的免疫反应性IGF结合蛋白-3（IGFBP-3）水平更高。Western免疫印迹显示，IGFBP-3的明显增加主要是由于免疫反应性片段增加。IGFBP-3蛋白酶活性未增加。因此，IGFBP片段积累可能反映了片段清除减少。Western配体印迹显示CRF血清中30和34kDa的IGFBP水平及IGFBP产物升高。CRF患者血清酸不稳定亚基水平未改变。两组间游离IGF-1的峰值水平和MCR无差异。在两组中，游离IGF-1的MCR比总IGF-1的MCR高约30倍。这些数据表明，在接受皮下注射IGF-1的CRF患者中：（a）血清总IGF-1水平因循环IGFBPs升高而增加，这可能会限制IGF-1在血浆外的分布；（b）血清游离IGF-1水平未改变；（c）CRF患者的IGF-1 MCR未改变。因此，在晚期CRF中，除了总IGF-1分布容积减少外，IGF-1的药代动力学基本未改变。
