Indoxyl sulfate: clinical implications for anemia management in chronic kidney disease
Issued Date
2025-12-08
Resource Type
ISSN
10624821
eISSN
14736543
Scopus ID
2-s2.0-105031855378
Pubmed ID
41355384
Journal Title
Current Opinion in Nephrology and Hypertension
Volume
Publish Ahead of Print
Rights Holder(s)
SCOPUS
Bibliographic Citation
Current Opinion in Nephrology and Hypertension Vol.Publish Ahead of Print (2025)
Suggested Citation
Rattanasompattikul M., Srithongkul T., Tantisattamo E., Kalantar-Zadeh K., Noppakun K. Indoxyl sulfate: clinical implications for anemia management in chronic kidney disease. Current Opinion in Nephrology and Hypertension Vol.Publish Ahead of Print (2025). doi:10.1097/MNH.0000000000001145 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115711
Title
Indoxyl sulfate: clinical implications for anemia management in chronic kidney disease
Author's Affiliation
University of California, Irvine
Chiang Mai University
Siriraj Hospital
UCI Medical Center
The Lundquist Institute
Faculty of Medicine Ramathibodi Hospital, Mahidol University
VA Long Beach Healthcare System
Oakland University William Beaumont School of Medicine
Pacific Northwest University of Health Sciences
Faculty of Medicine
Chiang Mai University
Siriraj Hospital
UCI Medical Center
The Lundquist Institute
Faculty of Medicine Ramathibodi Hospital, Mahidol University
VA Long Beach Healthcare System
Oakland University William Beaumont School of Medicine
Pacific Northwest University of Health Sciences
Faculty of Medicine
Corresponding Author(s)
Other Contributor(s)
Abstract
Purpose of review – This review examines the role of indoxyl sulfate, a gut-derived uremic toxin, in the development of anemia in chronic kidney disease. It dissects the cellular and biochemical mechanisms through which indoxyl sulfate suppresses erythropoietin production, disrupts iron metabolism, and promotes oxidative stress and inflammation. Recent findings – Indoxyl sulfate interferes directly with the hypoxia-inducible factor pathway, thereby reducing the transcriptional activation of erythropoietin. In parallel, indoxyl sulfate-induced oxidative stress damages red blood cells and accelerates premature cell death, while its stimulation of pro-inflammatory pathways further downregulates erythroid progenitor cell function. Therapeutic strategies such as dietary protein modulation, gut microbiota interventions, oral adsorbents, and enhanced dialysis modalities have shown promise in lowering indoxyl sulfate levels and, consequently, improving erythropoietin responsiveness and iron homeostasis in chronic kidney disease patients. Summary – The review synthesizes evidence from clinical and experimental studies that position indoxyl sulfate as a central yet underappreciated mediator of anemia in chronic kidney disease. Indoxyl sulfate establishes a vicious cycle that exacerbates anemia and contributes to erytropoiesis-stimulating agent hyporesponsiveness. The article advocates for targeted interventions aimed at reducing indoxyl sulfate burden, which could transform anemia management in chronic kidney disease and pave the way for personalized treatment strategies.