{"doi":"10.34067/kid.0003942020","title":"Randomized, Placebo-Controlled Trial of Rifaximin Therapy for Lowering Gut-Derived Cardiovascular Toxins and Inflammation in CKD","abstract":"Background Recent evidence suggests the systemic accumulation of by-products of gut microbes contributes to cardiovascular morbidity in patients with CKD. Limiting the generation of toxic bacterial by-products by manipulating the intestinal microbiota may be a novel strategy for reducing cardiovascular disease in CKD. Rifaximin is a minimally absorbed, oral antibiotic that targets intestinal pathogens and is commonly used as chronic therapy for the prevention of encephalopathy in patients with cirrhosis. Methods We conducted a randomized, double-blinded, placebo-controlled trial to determine the effect of a 10-day course of oral rifaximin 550 mg BID versus placebo on circulating concentrations of gut-derived cardiovascular toxins and proinflammatory cytokines in patients with stage 3–5 CKD ( n =38). The primary clinical outcome was change in serum trimethylamine N -oxide (TMAO) concentrations from baseline to study end. Secondary outcomes included change in serum concentrations of p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines (C-reactive protein, IL-6, IL-1 β ), and change in composition and diversity of fecal microbiota. Results A total of 19 patients were randomized to each of the rifaximin and placebo arms, with n =17 and n =14 completing both study visits in these respective groups. We observed no difference in serum TMAO change (post-therapy minus baseline TMAO) between the rifaximin and placebo groups (mean TMAO change −3.9±15.4 for rifaximin versus 0.5±9.5 for placebo, P =0.49). Similarly, we found no significant change in serum concentrations for p-cresol sulfate, indoxyl sulfate, kynurenic acid, deoxycholic acid, and inflammatory cytokines. We did observe differences in colonic bacterial communities, with the rifaximin group exhibiting significant decreases in bacterial richness (Chao1, P =0.02) and diversity (Shannon H, P =0.05), along with altered abundance of several bacterial genera. Conclusions Short-term rifaximin treatment failed to reduce gut-derived cardiovascular toxins and inflammatory cytokines in patients with CKD. Clinical Trial registry name and registration number Rifaximin Therapy in Chronic Kidney Disease, NCT02342639","journal":"Kidney360","year":2020,"id":68568,"datarank":0.8168664048899712,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.3465422725005987,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.3465422725005987,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":22,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02342639"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363539,"name":"Shiqin Zhang","orcid":"0000-0002-9847-5658","position":1,"is_corresponding":false},{"id":365276,"name":"Cassandra Johnson","orcid":null,"position":2,"is_corresponding":false},{"id":363540,"name":"Raymond E. West","orcid":"0000-0002-6362-8837","position":3,"is_corresponding":false},{"id":363541,"name":"Alexander J. Prokopienko","orcid":"0000-0002-8828-8365","position":4,"is_corresponding":false},{"id":296471,"name":"Jonathan D. Mahnken","orcid":null,"position":5,"is_corresponding":false},{"id":270870,"name":"Alan S.L. Yu","orcid":"0000-0002-1776-2533","position":6,"is_corresponding":false},{"id":788,"name":"Andrew N. Hoofnagle","orcid":"0000-0002-6449-0243","position":7,"is_corresponding":false},{"id":256913,"name":"Diana Ir","orcid":null,"position":8,"is_corresponding":false},{"id":254439,"name":"Charles E. Robertson","orcid":"0000-0002-4136-4121","position":9,"is_corresponding":false},{"id":363542,"name":"Makoto Miyazaki","orcid":"0000-0002-8704-8511","position":10,"is_corresponding":false},{"id":110793,"name":"Michel Chonchol","orcid":null,"position":11,"is_corresponding":false},{"id":365277,"name":"Anna Jovanovich","orcid":null,"position":12,"is_corresponding":false},{"id":268748,"name":"Bryan Kestenbaum","orcid":"0000-0003-4799-5968","position":13,"is_corresponding":false},{"id":254434,"name":"Daniel N. Frank","orcid":"0000-0001-6669-228X","position":14,"is_corresponding":false},{"id":363543,"name":"Thomas D. Nolin","orcid":"0000-0003-4339-1382","position":15,"is_corresponding":false},{"id":363544,"name":"Jason R. Stubbs","orcid":"0000-0003-4580-5745","position":16,"is_corresponding":false},{"id":365275,"name":"Cassandra Kimber","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-18T21:41:52.279368Z","pmid":"34322673","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}