Behnisch Rouven, Kirchner Marietta, Anarat Ali, Bacchetta Justine, Shroff Rukshana, Bilginer Yelda, Mir Sevgi, Caliskan Salim, Paripovic Dusan, Harambat Jerome, Mencarelli Francesca, Büscher Rainer, Arbeiter Klaus, Soylemezoglu Oguz, Zaloszyc Ariane, Zurowska Aleksandra, Melk Anette, Querfeld Uwe, Schaefer Franz
Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Department of Pediatric Nephrology, School of Medicine, Cukurova University, Adana, Turkey.
Front Pediatr. 2019 Jul 5;7:278. doi: 10.3389/fped.2019.00278. eCollection 2019.
Failure of statural growth is one of the major long-term sequelae of chronic kidney disease (CKD) in children. In recent years effective therapeutic strategies have become available that lead to evidence based practice recommendations. To assess the current growth performance of European children and adolescents with CKD, we analyzed a cohort of 594 patients from 12 European countries who were followed prospectively for up to 6 years in the 4C Study. While all patients were on conservative treatment with a mean estimated glomerular filtration rate of 28 ml/min/1.73 m at study entry, 130 children commenced dialysis during the observation period. At time of enrolment the mean height standard deviation score (SDS) was -1.57; 36% of patients had a height below the third percentile. The prevalence of growth failure varied between countries from 7 to 44% Whereas patients on conservative treatment showed stable growth, height SDS gradually declined on those on dialysis. Parental height, pubertal status and treatment with recombinant growth hormone (GH) were positively, and the diagnosis of syndromic disease and CKD stage were negatively associated with height SDS during the observation period. Unexpectedly, higher body mass index (BMI) SDS was associated with lower height SDS both at enrolment and during follow up. Renal anemia, metabolic acidosis, and hyperparathyroidism were mostly mild and not predictive of growth rates by multivariable analysis. GH therapy was applied in only 15% of growth retarded patients with large variation between countries. When adjusting for all significant covariates listed above, the country of residence remained a highly significant predictor of overall growth performance. In conclusion, growth failure remains common in European children with CKD, despite improved general management of CKD complications. The widespread underutilization of GH, an approved efficacious therapy for CKD-associated growth failure, deserves further exploration.
身材生长发育迟缓是儿童慢性肾脏病（CKD）的主要长期后遗症之一。近年来，已有有效的治疗策略，可据此形成基于证据的实践建议。为评估欧洲CKD儿童和青少年的当前生长发育情况，我们分析了来自12个欧洲国家的594例患者队列，这些患者在4C研究中接受了长达6年的前瞻性随访。所有患者在研究开始时均接受保守治疗，平均估计肾小球滤过率为28 ml/min/1.73 m²，130名儿童在观察期内开始透析。入组时平均身高标准差评分（SDS）为-1.57；36%的患者身高低于第三百分位数。身材生长发育迟缓的患病率在不同国家之间为7%至44%。接受保守治疗的患者生长稳定，而透析患者的身高SDS逐渐下降。在观察期内，父母身高、青春期状态和重组生长激素（GH）治疗与身高SDS呈正相关，综合征疾病诊断和CKD分期与身高SDS呈负相关。出乎意料的是，较高的体重指数（BMI）SDS在入组时和随访期间均与较低的身高SDS相关。肾性贫血、代谢性酸中毒和甲状旁腺功能亢进大多较轻，多变量分析显示它们不能预测生长速度。只有15%生长发育迟缓的患者接受了GH治疗，不同国家之间差异很大。在对上述所有显著协变量进行校正后，居住国仍然是总体生长发育情况的高度显著预测因素。总之，尽管CKD并发症的总体管理有所改善，但身材生长发育迟缓在欧洲CKD儿童中仍然很常见。GH作为一种已获批准的治疗CKD相关生长发育迟缓的有效疗法，其广泛未得到充分利用的情况值得进一步探讨。
