Doyon Anke, Fischer Dagmar-Christiane, Bayazit Aysun Karabay, Canpolat Nur, Duzova Ali, Sözeri Betül, Bacchetta Justine, Balat Ayse, Büscher Anja, Candan Cengiz, Cakar Nilgun, Donmez Osman, Dusek Jiri, Heckel Martina, Klaus Günter, Mir Sevgi, Özcelik Gül, Sever Lale, Shroff Rukshana, Vidal Enrico, Wühl Elke, Gondan Matthias, Melk Anette, Querfeld Uwe, Haffner Dieter, Schaefer Franz
Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
Department of Pediatrics, University Hospital Rostock, Rostock, Germany.
PLoS One. 2015 Feb 6;10(2):e0113482. doi: 10.1371/journal.pone.0113482. eCollection 2015.
The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort.
Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group.
Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score.
Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.
慢性肾脏病患儿骨代谢改变对其身高增长的影响程度及相关性存在争议。我们在一个大型儿科慢性肾脏病队列中分析了肾功能不全和重组生长激素治疗对一组骨代谢血清标志物的影响。
对556名6 - 18岁、估计肾小球滤过率（eGFR）为10 - 60 ml/min/1.73 m²的儿童，分析经年龄和性别校正后的骨碱性磷酸酶（BAP）、抗酒石酸酸性磷酸酶5b（TRAP5b）、硬化蛋白和C末端成纤维细胞生长因子23（cFGF23）。将41名接受重组生长激素治疗的儿童与未治疗的匹配对照组进行比较。
BAP、TRAP5b和cFGF - 23的标准化水平升高，而硬化蛋白降低。BAP与eGFR呈正相关，cFGF - 23与eGFR呈负相关。血清全段甲状旁腺激素是BAP和TRAP5b的独立阳性预测因子，与硬化蛋白呈负相关。BAP和TRAP5B受到C反应蛋白水平升高的负面影响。接受重组生长激素治疗的儿童，其BAP高于未治疗对照组，TRAP5b低于未治疗对照组。硬化蛋白水平在正常范围内且高于未治疗对照组。血清硬化蛋白和cFGF - 23独立预测身高标准差评分，BAP和TRAP5b预测身高标准差评分的预期变化。
骨代谢标志物表明慢性肾脏病患儿处于高骨转换状态。生长激素诱导骨合成代谢模式并使骨细胞活性正常化。骨细胞标志物cFGF23和硬化蛋白与标准化身高相关，骨转换标志物预测身高增长速度。
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