Abstract
Background and aimNumerous 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.MethodsProspectively 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.ResultsConcentrations 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.ConclusionIntra-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.
Highlights
Chronic kidney disease is characterized by the retention of numerous solutes, which are at the origin of a deterioration of multiple biochemical and physiological functions [1, 2]
A substantial spontaneous background fluctuation of concentrations of uremic toxins within one patient over time might have an impact on the interpretation of this type of studies, whereby the effect can be both overor underestimated purely based on chance. It has not been investigated in a systematic way whether predialysis concentrations of uremic toxins remain constant in stable hemodialysis patients over a given time period
During the entire study period, the dialysis mode, dialyzer blood and dialysate flows and hemodialyzer type were maintained stable in each patient, i.e. two-needle/lumen post dilution hemodiafiltration with high flux dialyzers: FX800 (n = 12) (Fresenius Medical Care, Germany), Phylter HF 17G (n = 2) (Bellco, Italy), Sureflux 170 (n = 1) (Nipro Europe, Belgium), Xenium 210 (n = 1), Polyflux 170H (n = 1) and Evodial 1.3 (n = 1)
Summary
Chronic kidney disease is characterized by the retention of numerous solutes, which are at the origin of a deterioration of multiple biochemical and physiological functions [1, 2]. A substantial spontaneous background fluctuation of concentrations of uremic toxins within one patient over time might have an impact on the interpretation of this type of studies, whereby the effect can be both overor underestimated purely based on chance. 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 entirely depends on how representative these cross-sectional concentrations are. We investigated the variability of predialysis concentrations of uremic toxins over time
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