Department of Paediatrics and Medical Genetics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Nephrol Dial Transplant. 2018 Jun 1;33(6):978-986. doi: 10.1093/ndt/gfx224.
Chronic kidney disease (CKD) in childhood is poorly explained by routine markers (e.g. urea and creatinine) and is better depicted in adults by other uraemic toxins. This study describes concentrations of representative uraemic toxins in non-dialysis CKD versus healthy children.
In 50 healthy children and 57 children with CKD Stages 1-5 [median estimated glomerular filtration rate 48 (25th-75th percentile 24-71) mL/min/1.73 m2; none on dialysis], serum concentrations of small solutes [symmetric and asymmetric dimethyl-arginine (SDMA and ADMA, respectively)], middle molecules [β2-microglobuline (β2M), complement factor D (CfD)] and protein-bound solutes [p-cresylglucuronide (pCG), hippuric acid (HA), indole-acetic acid (IAA), indoxyl sulphate (IxS), p-cresyl sulphate (pCS) and 3-carboxy-4-methyl-5-propyl-furanpropionic acid (CMPF)] were measured. Concentrations in the CKD group were expressed as z-score relative to controls and matched for age and gender.
SDMA, CfD, β2M, IxS, pCS, IAA, CMPF and HA concentrations were higher in the overall CKD group compared with controls, ranging from 1.7 standard deviations (SD) for IAA and HA to 11.1 SD for SDMA. SDMA, CfD, β2M, IxS and CMPF in CKD Stages 1-2 with concentrations 4.8, 2.8, 4.5, 1.9 and 1.6 SD higher, respectively. In contrast, pCS, pCG and IAA concentrations were only higher than controls from CKD Stages 3-4 onwards, but only in CKD Stage 5 for ADMA and HA (z-score 2.6 and 20.2, respectively).
This is the first study to establish reference values for a wide range of uraemic toxins in non-dialysis CKD and healthy children. We observed an accumulation of multiple uraemic toxins, each with a particular retention profile according to the different CKD stages.
常规标志物（如尿素和肌酐）对儿童慢性肾脏病（CKD）的解释很差，而其他尿毒症毒素在成人中能更好地描述。本研究描述了非透析 CKD 与健康儿童相比代表性尿毒症毒素的浓度。
在 50 名健康儿童和 57 名 CKD 1-5 期儿童（中位估计肾小球滤过率 48（25-75 百分位 24-71）ml/min/1.73m2；无透析）中，测量血清中小溶质（对称和非对称二甲基精氨酸（SDMA 和 ADMA））、中分子（β2-微球蛋白（β2M）、补体因子 D（CfD））和蛋白结合溶质（p-对甲酚葡糖苷酸（pCG）、马尿酸（HA）、吲哚乙酸（IAA）、吲哚硫酸（IxS）、对甲酚硫酸盐（pCS）和 3-羧基-4-甲基-5-丙基-呋喃丙酸（CMPF）的浓度。CKD 组的浓度用与对照组相比的 z 分数表示，并按年龄和性别匹配。
SDMA、CfD、β2M、IxS、pCS、IAA、CMPF 和 HA 浓度在整个 CKD 组中均高于对照组，范围从 IAA 和 HA 的 1.7 个标准差（SD）到 SDMA 的 11.1 SD。CKD 1-2 期的 SDMA、CfD、β2M、IxS 和 CMPF 浓度分别高出 4.8、2.8、4.5、1.9 和 1.6 SD。相比之下，只有在 CKD 3-4 期以后，pCS、pCG 和 IAA 浓度才高于对照组，而 ADMA 和 HA 仅在 CKD 5 期才高于对照组（z 分数分别为 2.6 和 20.2）。
这是第一项在非透析 CKD 和健康儿童中建立多种尿毒症毒素参考值的研究。我们观察到多种尿毒症毒素的积累，每种毒素根据不同的 CKD 阶段具有特定的保留特征。
