Abstract
KEY POINTS: Significant differences in 39 plasma metabolites were observed between patients on extended-hours hemodialysis and those on conventional hemodialysis. Extended-hours hemodialysis had a lower lactate-to-pyruvate ratio and higher branched-chain amino acids than conventional hemodialysis. Extended-hours hemodialysis may have favorable metabolic and nutritional benefits for patients undergoing maintenance hemodialysis. BACKGROUND: Protein–energy wasting, characterized by disordered body protein catabolism resulting from metabolic and nutritional derangements, is associated with adverse clinical outcomes in patients undergoing hemodialysis. Extended-hours hemodialysis (≥6 hours per treatment session) offers both enhanced removal of uremic solutes and better fluid management, generally allowing more liberalized dietary protein and calorie intake. The aim of this study was to evaluate the difference in plasma metabolite profiles among patients receiving in-center daytime extended-hours hemodialysis and those receiving conventional hemodialysis. METHODS: Predialysis plasma samples were obtained from 188 patients on extended-hours hemodialysis (21.9 h/wk) and 286 patients on conventional hemodialysis (12.1 h/wk) in Japan in 2020 using capillary electrophoresis-mass spectrometry. Group differences were compared for 117 metabolites using Wilcoxon rank-sum tests with multiple comparisons and partial least squares discriminant analysis. In addition, propensity score–adjusted multiple regression analyses were performed to evaluate group differences for known uremic toxins, branched-chain amino acids, and lactate-to-pyruvate ratio (a possible surrogate marker of mitochondrial dysfunction). RESULTS: Significant differences were observed in 39 metabolites, largely consistent with the high variable importance for prediction in partial least squares discriminant analysis. Among known uremic toxins, uridine and hypoxanthine levels were significantly higher in the conventional hemodialysis group than in the extended-hours hemodialysis group, whereas trimethylamine N-oxide levels were higher in the extended-hours hemodialysis group than in the conventional hemodialysis group. Patients on extended-hours hemodialysis had higher levels of all branched-chain amino acids and a lower lactate-to-pyruvate ratio than those on conventional hemodialysis (significant difference of −8.6 [95% confidence interval, −9.8 to −7.4]). CONCLUSIONS: Extended-hours hemodialysis was associated with a more favorable plasma metabolic and amino acid profile; however, concentrations of most uremic toxins did not significantly differ from those of conventional hemodialysis.