Tönshoff B, Blum W F, Wingen A M, Mehls O
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
J Clin Endocrinol Metab. 1995 Sep;80(9):2684-91. doi: 10.1210/jcem.80.9.7545697.
Serum levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF binding protein 1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured in 94 children with chronic renal failure (CRF). The results were compared with their respective age-dependent normal ranges, and the relationship with height and residual glomerular filtration rate (GFR) was examined. Each IGF and IGFBP was quantified by specific RIA. Serum IGF-I and IGF-II levels were in the normal range throughout their entire childhood in the vast majority of cases. The mean age-related IGF-I (0.07 +/- 0.14 SD score) and IGF-II levels (0.06 +/- 0.11 SD) were similar. Age-related IGF-II but not IGF-I levels showed a weak inverse linear correlation with residual GFRs (r = -0.24, P < 0.02). Mean age-related IGFBP-1 serum levels (1.04 +/- 0.09 SD) were slightly elevated, whereas mean age-related serum IGFBP-2 levels (3.25 +/- 0.20 SD) and serum IGFBP-3 levels (2.61 +/- 0.12 SD) were markedly elevated. Significant inverse correlations were found between GFRs and age-related IGFBP-1 (r = -0.42, P < 0.001), IG-FBP-2 (r = -0.56, P < 0.001), and IGFBP-3 (r = -0.28, P < 0.005), but the increase in IGFBP-2 with declining GFR was relatively more pronounced than the respective increase in IGFBP-1 and IGFBP-3. The correlation between age-related IGF-I and relative height in prepubertal children with CRF (n = 54, r = 0.43, P < 0.001) was lower than in prepubertal controls (n = 68, r = 0.67, P < 0.001), and the slope of the regression line was significantly less steep, indicating that the normal relationship between IGF-I and height is disturbed in CRF. The normal relationship between IGFBP-3 and height was disrupted in CRF. Forward stepwise regression analysis revealed that height in CRF is correlated with IGF-I and inversely correlated with IGFBP-2. We conclude that the imbalance between normal IGFs and excessive IGFBP serum levels in CRF plays a pathogenic role in the growth failure of these children.
对94例慢性肾功能衰竭（CRF）患儿测定了血清胰岛素样生长因子I（IGF-I）、IGF-II以及IGF结合蛋白1（IGFBP-1）、IGFBP-2和IGFBP-3的水平。将结果与其各自年龄相关的正常范围进行比较，并研究其与身高和残余肾小球滤过率（GFR）的关系。每种IGF和IGFBP均通过特异性放射免疫分析（RIA）进行定量。在绝大多数情况下，血清IGF-I和IGF-II水平在整个儿童期均处于正常范围。与年龄相关的IGF-I平均水平（标准差评分0.07±0.14）和IGF-II水平（标准差0.06±0.11）相似。与年龄相关的IGF-II水平而非IGF-I水平与残余GFR呈弱的负线性相关（r = -0.24，P < 0.02）。与年龄相关的IGFBP-1血清平均水平（1.04±0.09标准差）略有升高，而与年龄相关的血清IGFBP-2平均水平（3.25±0.20标准差）和血清IGFBP-3平均水平（2.61±0.12标准差）显著升高。在GFR与年龄相关的IGFBP-1（r = -0.42，P < 0.001）、IGFBP-2（r = -0.56，P < 0.001）和IGFBP-3（r = -0.28，P < 0.005）之间发现了显著的负相关，但随着GFR下降，IGFBP-2的升高相对比IGFBP-1和IGFBP-3的相应升高更为明显。CRF青春期前儿童（n = 54，r = 0.43，P < 0.001）中与年龄相关的IGF-I和相对身高之间的相关性低于青春期前对照组（n = 68，r = 0.67，P < 0.001），且回归线的斜率明显更平缓，表明CRF中IGF-I与身高之间的正常关系受到干扰。CRF中IGFBP-3与身高之间的正常关系也被破坏。向前逐步回归分析显示，CRF中的身高与IGF-I相关且与IGFBP-2呈负相关。我们得出结论，CRF中正常IGF与过高的IGFBP血清水平之间的失衡在这些儿童的生长发育迟缓中起致病作用。
