Alterations in gut microbiota among maintenance hemodialysis patients with CKD-associated pruritus: a cross-sectional comparative study of two cohorts.

OBJECTIVE: Chronic kidney disease-associated pruritus (CKD-aP) is a common and burdensome complication in patients receiving maintenance hemodialysis (MHD), but its pathogenesis remains incompletely understood. This study aimed to characterize gut microbial differences between MHD patients with active CKD-aP and those without active pruritus. METHODS: In this single-center cross-sectional study, 89 patients receiving MHD were enrolled, including 45 with active CKD-aP (HDUP) and 44 without active pruritus (HDNUP). Fecal samples were analyzed using 16S rRNA gene sequencing. Microbial diversity, taxonomic composition, differentially abundant taxa, and predicted functional profiles were compared between groups. Multivariable association analysis was performed using MaAsLin2 at the phylum, class, order, family, genus, and species levels, with adjustment for age, sex, post-dialysis dry weight, dialysis vintage, the presence of diabetes mellitus, and a documented history of hyperphosphataemia. RESULTS: Alpha-diversity indices did not differ significantly between groups. Bray-Curtis-based analysis of similarities showed no difference in overall community structure (R = -0.00463, p = 0.5882), whereas unweighted UniFrac-based analysis detected a statistically significant but very small difference (R = 0.03449, p = 0.0183). Fourteen genera showed nominal differences in univariable analyses. After multivariable adjustment and false-discovery-rate (FDR) correction, significant associations were identified only at the family and order levels. Parasutterella showed a nominal genus-level association but did not remain statistically significant after FDR correction. LEfSe identified 31 candidate differentially enriched taxonomic features. PICRUSt2 analysis suggested nominal differences in six predicted pathways, including higher predicted protein digestion and absorption in HDNUP and higher predicted RIG-I-like receptor signaling and ether lipid metabolism in HDUP. CONCLUSION: Active CKD-aP was associated with selective differences in gut microbial relative abundance rather than broad alterations in microbial richness, diversity, or dominant community structure. Parasutterella showed a nominal genus-level association with the absence of active pruritus, although this association did not remain statistically significant after FDR correction. Other taxonomic and predicted functional findings were exploratory and require validation in longitudinal, multicenter studies incorporating absolute microbial quantification and metabolomic analyses.