Ghent University Hospital, 9000 Ghent, Belgium.
Biostatistics Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Toxins (Basel). 2024 Aug 9;16(8):349. doi: 10.3390/toxins16080349.
To promote improved trial design in upcoming randomized clinical trials in childhood chronic kidney disease (CKD), insight in the within- and inter-patient variability of uremic toxins with its nutritional, treatment- and patient-related confounding factors is of utmost importance. In this study, the within- and inter-patient variability of a selection of uremic toxins in a longitudinal cohort of children diagnosed with CKD was assessed, using the intraclass correlation coefficient (ICC) and the within-patient coefficient of variation (CV). Subsequently, the contribution of anthropometry, estimated glomerular filtration rate (eGFR), dietary fiber and protein, and use of (prophylactic) antibiotics to uremic toxin variability was evaluated. Based on 403 observations from 62 children (median seven visits per patient; 9.4 ± 5.3 years; 68% males; eGFR 38.5 [23.1; 64.0] mL/min/1.73 m) collected over a maximum of 2 years, we found that the within-patient variability is high for especially protein-bound uremic toxins (PBUTs) (ICC < 0.7; within-patient CV 37-67%). Moreover, eGFR was identified as a predominant contributor to the within- and inter-patient variability for the majority of solutes, while the impact of the child's anthropometry, fiber and protein intake, and antibiotics on the variability of uremic toxin concentrations was limited. Based on these findings, we would recommend future intervention studies that attempt to decrease uremic toxin levels to select a (non-dialysis) CKD study population with a narrow eGFR range. As the expected effect of the selected intervention should exceed the inter-patient variability of the selected uremic toxins, a narrow eGFR range might aid in improving the trial design.
为了提高即将开展的儿童慢性肾脏病（CKD）随机临床试验的设计水平，深入了解尿毒症毒素及其营养、治疗和患者相关混杂因素的个体内和个体间变异性至关重要。在这项研究中，我们使用组内相关系数（ICC）和个体内变异系数（CV）评估了 62 名确诊 CKD 儿童的纵向队列中一组尿毒症毒素的个体内和个体间变异性，并评估了人体测量学、估算肾小球滤过率（eGFR）、膳食纤维和蛋白质以及（预防性）抗生素的使用对尿毒症毒素变异性的影响。该研究共纳入 62 名儿童的 403 次观察结果（每名患者的中位数随访次数为 7 次；年龄为 9.4 ± 5.3 岁；68%为男性；eGFR 为 38.5 [23.1；64.0] mL/min/1.73 m2），随访时间最长为 2 年。结果发现，尤其对于蛋白结合尿毒症毒素（PBUT），个体内变异性较高（ICC < 0.7；个体内 CV 为 37-67%）。此外，eGFR 是大多数溶质个体内和个体间变异性的主要影响因素，而儿童人体测量学、纤维和蛋白质摄入以及抗生素对尿毒症毒素浓度变异性的影响有限。基于这些发现，我们建议未来的干预研究尝试降低尿毒症毒素水平，以选择 eGFR 范围较窄的（非透析）CKD 研究人群。由于所选干预措施的预期效果应超过所选尿毒症毒素的个体间变异性，因此较窄的 eGFR 范围可能有助于改善试验设计。
