Pediatric Nephrology, Hospital Universitario Central de Asturias, University of Oviedo, Oviedo, Asturias, Spain.
Pediatr Nephrol. 2010 Apr;25(4):733-7. doi: 10.1007/s00467-009-1330-7. Epub 2009 Nov 10.
Growth retardation remains a major complication in children with primary tubular disorders, despite adequate supplemental treatment with electrolytes, water and bicarbonate. Chronic hypokalemia, characteristic of some tubulopathies, impairs growth by mechanisms that are not well known. Association with growth hormone deficiency has been reported in patients with Bartter's or Gitelman's syndrome. Tissue-specific alterations of growth hormone and insulin-like growth factor I axis have been described in experimental models of potassium depletion. Hypokalemic rats gain less body length and weight than pair-fed normokalemic animals and, by contrast, develop renal hypertrophy. These rats have low circulating concentrations of insulin-like growth factor I, depressed messenger ribonucleic acid (mRNA) levels of this peptide in the tibial growth plate, and they are resistant to the longitudinal growth-promoting effects of exogenous growth hormone. The reason for this resistance remains to be defined. No alterations in the intracellular signaling for growth hormone have been found in the liver of hypokalemic rats. However, treatment with high doses of growth hormone is unable to normalize hypertrophy of the epiphyseal cartilage chondrocytes, which are severely disturbed in potassium depletion and likely play an important role in the pathogenia of growth impairment in this condition.
尽管在电解质、水和碳酸氢盐方面进行了适当的补充治疗,但原发性肾小管疾病患儿仍存在生长迟缓这一主要并发症。某些肾小管疾病的特征是慢性低钾血症,其通过尚未完全明确的机制来影响生长。巴特氏综合征或吉特曼综合征患者存在生长激素缺乏症的报道。在钾耗竭的实验模型中已经描述了生长激素和胰岛素样生长因子 I 轴的组织特异性改变。低钾血症大鼠比等热量喂养的正常血钾动物体长得少,体重增加得少,而且还会发生肾脏肥大。这些大鼠的循环胰岛素样生长因子 I 浓度较低,胫骨生长板中这种肽的信使核糖核酸(mRNA)水平降低,并且它们对生长激素的纵向生长促进作用有抗性。这种抗性的原因仍有待确定。在低钾血症大鼠的肝脏中未发现生长激素的细胞内信号转导改变。然而,高剂量生长激素治疗无法使骨骺软骨细胞的肥大正常化,在钾耗竭时,这些软骨细胞严重紊乱,可能在这种情况下生长受损的发病机制中发挥重要作用。