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Association of gut microbiome signatures with iron metabolism response to roxadustat in peritoneal dialysis patients with anemia: a cross-sectional study

Jiang-Qing Fan, Xinqi Tan, Ying Liu, Zhe Liu, Jialing Dai, Lu-Lu Wang

Frontiers in Pharmacology, 2026

Abstract

Background Anemia in chronic kidney disease (CKD) is associated with increased cardiovascular risk, impaired quality of life, and reduced survival. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), has demonstrated non-inferior efficacy to erythropoiesis-stimulating agents (ESAs) for anemia correction in CKD. Gut microbiota modulate the intestinal HIF-iron metabolism axis, thereby regulating intestinal iron absorption. This cross-sectional study investigated the association between gut microbiome composition and iron-metabolism response to roxadustat, and developed a logistic regression model to identify factors associated with iron metabolism non-response in anemic patients undergoing peritoneal dialysis (PD). Methods Demographic and clinical data were collected at study enrollment, and fecal samples underwent 16S rRNA gene sequencing. Microbial taxa associated with the iron-metabolism response to roxadustat were identified using linear discriminant analysis effect size (LEfSe), differential abundance analysis with DESeq2, and Spearman’s rank correlation analysis. Key microbial features were further selected using random forest analysis. Multivariable logistic regression models were constructed using R software (version 4.2.3). Variable selection was performed through stepwise selection based on the Akaike information criterion. Model performance was evaluated with the area under the receiver operating characteristic curve, calibration curves,…

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Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.

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