Eloot Sunny, Van Biesen Wim, Roels Sanne, Delrue Willem, Schepers Eva, Dhondt Annemieke, Vanholder Raymond, Glorieux Griet
Department of Nephrology, Ghent University Hospital, Gent, Belgium.
Department of Data Analysis, Ghent University, Gent, Belgium.
PLoS One. 2017 Oct 10;12(10):e0186010. doi: 10.1371/journal.pone.0186010. eCollection 2017.
Numerous outcome studies and interventional trials in hemodialysis (HD) patients are based on uremic toxin concentrations determined at one single or a limited number of time points. The reliability of these studies however entirely depends on how representative these cross-sectional concentrations are. We therefore investigated the variability of predialysis concentrations of uremic toxins over time.
Prospectively collected predialysis serum samples of the midweek session of week 0, 1, 2, 3, 4, 8, 12, and 16 were analyzed for a panel of uremic toxins in stable chronic HD patients (N = 18) while maintaining dialyzer type and dialysis mode during the study period.
Concentrations of the analyzed uremic toxins varied substantially between individuals, but also within stable HD patients (intra-patient variability). For urea, creatinine, beta-2-microglobulin, and some protein-bound uremic toxins, Intra-class Correlation Coefficient (ICC) was higher than 0.7. However, for phosphorus, uric acid, symmetric and asymmetric dimethylarginine, and the protein-bound toxins hippuric acid and indoxyl sulfate, ICC values were below 0.7, implying a concentration variability within the individual patient even exceeding 65% of the observed inter-patient variability.
Intra-patient variability may affect the interpretation of the association between a single concentration of certain uremic toxins and outcomes. When performing future outcome and interventional studies with uremic toxins other than described here, one should quantify their intra-patient variability and take into account that for solutes with a large intra-patient variability associations could be missed.
众多针对血液透析（HD）患者的结局研究和干预试验是基于在单个或有限数量时间点测定的尿毒症毒素浓度。然而，这些研究的可靠性完全取决于这些横断面浓度的代表性如何。因此，我们调查了尿毒症毒素透析前浓度随时间的变异性。
对稳定的慢性HD患者（N = 18）在第0、1、2、3、4、8、12和16周周中透析时段前瞻性收集的透析前血清样本进行一组尿毒症毒素分析，研究期间保持透析器类型和透析模式不变。
所分析的尿毒症毒素浓度在个体之间差异很大，在稳定的HD患者中也存在差异（患者内变异性）。对于尿素、肌酐、β2微球蛋白和一些与蛋白结合的尿毒症毒素，组内相关系数（ICC）高于0.7。然而，对于磷、尿酸、对称和不对称二甲基精氨酸以及与蛋白结合的毒素马尿酸和硫酸吲哚酚，ICC值低于0.7，这意味着个体患者内的浓度变异性甚至超过观察到的患者间变异性的65%。
患者内变异性可能会影响对某些尿毒症毒素单一浓度与结局之间关联的解释。在进行未来关于此处未描述的尿毒症毒素的结局和干预研究时，应量化其患者内变异性，并考虑到对于患者内变异性大的溶质，可能会遗漏关联。
