Hokken-Koelega A C, Stijnen T, de Muinck Keizer-Schrama S M, Blum W F, Drop S L
Department of Pediatrics, Sophia Children's Hospital/Erasmus University, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1993 Oct;77(4):932-8. doi: 10.1210/jcem.77.4.7691864.
Growth retardation after renal transplantation (RTx) is generally attributed to prednisone (PDN) administration, although the exact mechanism is poorly understood. In a group of 19 growth-retarded post-RTx children, we studied the effect of alternate day (AD; n = 12) and daily (D; n = 7) PDN therapy (0.10-0.25 mg/kg.day) on 24-h plasma GH and cortisol profiles, once in group D and twice on successive days in group AD. The maximal plasma GH response to arginine provocation (ATT) and plasma levels of insulin-like growth factor-I (IGF-I), IGF-II, and serum IGF-binding proteins (IGFBP) were also determined. The pulsatile character of the 24-h GH secretion was sustained in all patients. However, mean GH levels were significantly lower as compared with published data for healthy children, corrected for pubertal stage and sex. The highest mean GH levels were found in boys and girls in late puberty. Group AD had similar 24-h GH profiles whether on or off PDN treatment, which did not differ significantly from the GH profiles observed in group D. The maximal GH response during ATT was greater than 10 micrograms/L in 57% of the children. Group D had significantly lower mean and maximal cortisol levels than group AD, but all patients had a normal diurnal variation. Plasma immunoreactive IGF-I and IGF-II, and serum IGFBP-1 levels were normal, but serum levels of IGFBP-3 were increased. A significant negative correlation was found between the glomerular filtration rate and serum IGFBP-3 levels. In conclusion, our findings indicate that growth-retarded renal allograft patients, receiving either alternate day or daily PDN therapy, have decreased GH secretion, but a normal diurnal rhythm of GH and cortisol secretion as well as normal plasma IGF-I and -II levels. However, growth retardation after RTx may not solely be the result of decreased GH secretion. Renal graft impairment together with decreased IGF bioavailability may, in addition to the presumed direct effects of PDN on cartilage, contribute to the growth retardation after RTx.
肾移植（RTx）后生长发育迟缓通常归因于泼尼松（PDN）的使用，尽管其确切机制尚不清楚。在一组19例肾移植后生长发育迟缓的儿童中，我们研究了隔日（AD组，n = 12）和每日（D组，n = 7）给予PDN治疗（0.10 - 0.25mg/kg·天）对24小时血浆生长激素（GH）和皮质醇水平的影响，D组进行一次，AD组连续两天进行。还测定了对精氨酸激发试验（ATT）的最大血浆GH反应以及胰岛素样生长因子-I（IGF-I）、IGF-II和血清IGF结合蛋白（IGFBP）的血浆水平。所有患者24小时GH分泌的脉冲特征均得以维持。然而，与已发表的根据青春期阶段和性别校正后的健康儿童数据相比，平均GH水平显著降低。青春期晚期的男孩和女孩平均GH水平最高。AD组无论是否接受PDN治疗，其24小时GH水平相似，与D组观察到的GH水平无显著差异。57%的儿童在ATT期间最大GH反应大于10μg/L。D组的平均和最大皮质醇水平显著低于AD组，但所有患者的昼夜变化均正常。血浆免疫反应性IGF-I和IGF-II以及血清IGFBP-1水平正常，但血清IGFBP-3水平升高。肾小球滤过率与血清IGFBP-3水平之间存在显著负相关。总之，我们的研究结果表明，接受隔日或每日PDN治疗的生长发育迟缓的肾移植患者GH分泌减少，但GH和皮质醇分泌的昼夜节律正常，血浆IGF-I和-II水平也正常。然而，肾移植后生长发育迟缓可能不仅仅是GH分泌减少的结果。除了推测的PDN对软骨的直接作用外，肾移植功能损害以及IGF生物利用度降低可能也导致了肾移植后生长发育迟缓。
