Snauwaert Evelien, De Buyser Stefanie, Van Biesen Wim, Raes Ann, Glorieux Griet, Collard Laure, Van Hoeck Koen, Van Dyck Maria, Godefroid Nathalie, Walle Johan Vande, Eloot Sunny
Department of Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium.
Biostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Kidney Int Rep. 2024 Mar 26;9(6):1674-1683. doi: 10.1016/j.ekir.2024.03.021. eCollection 2024 Jun.
Growth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central to the pathophysiology of growth failure is the presence of a chronic proinflammatory state, presumed to be partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre)school-aged children and children during pubertal stages.
In a prospective, multicentric observational study, a selection of uremic toxin levels of children (aged 0-18 years) with CKD stage 1 to 5D was assessed every 3 months (maximum 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SD scores [SDS]). A piecewise linear association between age and height was assumed.
Data analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre)school aged children (aged 2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/yr ( < 0.05), given that CKD stage, growth hormone (GH), bicarbonate concentration, and dietary protein intake were held constant. No significant association with height velocity was found in children during pubertal stages (aged >12 years).
The present study demonstrated that, especially IxS contributes to a lower height velocity in (pre)school children, whereas we could not find a role for uremic toxins with height velocity during pubertal stages.
生长发育迟缓被认为是儿童慢性肾脏病（CKD）最重要的临床结局参数。生长发育迟缓病理生理学的核心是存在慢性促炎状态，推测部分是由尿毒症毒素的蓄积所致。在本研究中，我们评估了学龄前儿童和青春期儿童的纵向多中心前瞻性儿科CKD队列中尿毒症毒素浓度与身高增长速度之间的关联。
在一项前瞻性、多中心观察性研究中，每3个月（最长2年）评估一次1至5D期CKD儿童（0至18岁）的一系列尿毒症毒素水平以及临床生长参数。采用年龄随机斜率和儿童随机截距的线性混合模型对身高（以厘米和标准差评分[SDS]表示）进行拟合。假定年龄与身高之间存在分段线性关联。
数据分析纳入了81名儿童（中位年龄9.4岁；2/3为男性）的560次访视数据。在学龄前儿童（2至12岁）中，假设CKD分期、生长激素（GH）、碳酸氢盐浓度和膳食蛋白质摄入量保持不变，同时硫酸吲哚酚（IxS，总量）浓度增加10%会导致估计平均身高增长速度降低0.002 SDS/年（P<0.05）。在青春期儿童（年龄>12岁）中未发现与身高增长速度有显著关联。
本研究表明，尤其是IxS会导致学龄前儿童身高增长速度降低，而我们未发现尿毒症毒素在青春期儿童身高增长速度方面发挥作用。
