Department of Paediatrics and Medical Genetics, Faculty of Medicine and Health Sciences, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Pediatr Nephrol. 2018 Feb;33(2):315-323. doi: 10.1007/s00467-017-3802-5. Epub 2017 Sep 22.
Chronic kidney disease (CKD) in childhood is characterised by the accumulation of uraemic toxins resulting in a multisystem disorder that has a negative impact on quality of life. Childhood CKD is predominantly defined by a decrease in glomerular filtration rate, estimated (eGFR) by a single serum measurement of endogenous biomarkers, e.g. creatinine. The objective of this study was to evaluate how accurately eGFR predicts the concentration of uraemic toxins in a paediatric CKD cohort.
In 65 children (10.8 [5.1; 14.7] years) with CKD (eGFR 44 [20; 64] mL/min/1.73 m), serum concentrations were determined of small solutes (uric acid [UA], urea, symmetric dimethylarginine [SDMA], asymmetric dimethylarginine [ADMA]), middle molecules (β2-microglobulin [β2M], complement factor D [CfD]) and protein-bound solutes (p-cresylglucuronide [pCG], hippuric acid, indole acetic acid, indoxyl sulphate [IxS], p-cresylsulfate [pCS] and 3-carboxy-4-methyl-5-propyl-furanpropionic acid [CMPF]). Spearman's correlation coefficients (r) were calculated to correlate uraemic toxin concentrations with three different eGFR equations, based on either serum creatinine or β2M.
Updated Schwartz eGFR was correlated reasonably well with concentrations of creatinine (r = -0.98), urea (r = -0.84), SDMA (r = -0.82) and middle molecules CfD and β2M (both r = -0.90). In contrast, poor correlation coefficients were found for CMPF (r = -0.32), UA (r = -0.45), ADMA (r = -0.47) and pCG (r = -0.48). The other toxins, all protein-bound, had r between -0.75 and -0.57. Comparable correlations were found between the three evaluated eGFR equations and uraemic toxin concentrations.
This study demonstrates that eGFR poorly predicts concentrations of protein-bound uraemic toxins, UA and ADMA in childhood CKD. Therefore, eGFR only partially reflects the complexity of the accumulation pattern of uraemic toxins in childhood CKD.
儿童慢性肾脏病（CKD）的特征是尿毒症毒素的积累，导致多系统紊乱，对生活质量产生负面影响。儿童 CKD 主要由肾小球滤过率（GFR）下降定义，通过单次血清内源性生物标志物（如肌酐）测量来估计（eGFR）。本研究旨在评估 eGFR 在儿科 CKD 队列中预测尿毒症毒素浓度的准确性。
在 65 名 CKD 儿童（10.8[5.1；14.7]岁）中，测定血清中小溶质（尿酸[UA]、尿素、对称二甲基精氨酸[SDMA]、不对称二甲基精氨酸[ADMA]）、中分子（β2-微球蛋白[β2M]、补体因子 D [CfD]）和蛋白结合溶质（对羟苯甲酰葡糖醛酸[pCG]、马尿酸、吲哚乙酸、吲哚硫酸[IxS]、对羟苯甲酰硫酸[pCS]和 3-羧基-4-甲基-5-丙基-呋喃丙酸[CMPF]）的浓度。计算 Spearman 相关系数（r），以将尿毒症毒素浓度与基于血清肌酐或β2M 的三种不同 eGFR 方程相关联。
更新后的 Schwartz eGFR 与肌酐（r=-0.98）、尿素（r=-0.84）、SDMA（r=-0.82）和中分子 CfD 和β2M（均 r=-0.90）的浓度相关性较好。相比之下，CMPF（r=-0.32）、UA（r=-0.45）、ADMA（r=-0.47）和 pCG（r=-0.48）的相关系数较差。所有其他蛋白结合毒素的 r 值在-0.75 到-0.57 之间。三种评估的 eGFR 方程与尿毒症毒素浓度之间存在类似的相关性。
本研究表明，eGFR 对儿童 CKD 中蛋白结合尿毒症毒素、UA 和 ADMA 的浓度预测不佳。因此，eGFR 仅部分反映了儿童 CKD 中尿毒症毒素积累模式的复杂性。
