{"doi":"10.1681/asn.0000000675","title":"Uremic Toxins, CKD, and Cognitive Dysfunction","abstract":"Cognitive impairment involves alterations to one's cognitive status that affects everyday life. Individuals with CKD, and particularly kidney failure, experience higher rates of cognitive impairment (20%-70%) compared with the general population. The highest prevalence is described in kidney failure such that dialysis-dependent patients have twice the prevalence of age-matched controls. In the past 5 years, the number of investigations examining the \"kidney-brain axis,\" mechanisms of CKD-related cognitive impairment, and potential therapeutics have exponentially increased. This review article summarizes recent literature on direct and indirect effects of CKD-associated cognitive impairment with emphasis on uremic toxins; brain injury mechanisms; overlap between CKD-associated cognitive impairment, Alzheimer's disease, and other neurodegenerative diseases. Reviewed therapeutic interventions include AST-120 (indoxyl sulfate absorbent), CH-223191 (aryl hydrocarbon receptor antagonist), triarylmethane-34 (Kca3.1-specific inhibitor), anakinra (IL-1R inhibitor), marimastat, exercise, supplements, and kidney transplantation. Special focus is placed on translational studies examining uremic toxin-associated pathogenic processes, including brain oxidative stress, neuroinflammation, and blood-brain barrier dysfunction through in vitro and in vivo models of CKD-associated brain injury. Finally, future research directions are suggested, including targeting of cellular senescence abundance with senotherapeutics and capitalizing on anti-inflammatory effects of regenerative, cell-based therapeutics ( e.g ., mesenchymal stem cells and extracellular vesicles), and use of aged murine models. Collectively, CKD-associated cognitive impairment represents a prevalent condition for which remaining knowledge gaps exist, and scientific advancements are needed to preserve cognitive function and improve the lives of individuals with CKD.","journal":"Journal of the American Society of Nephrology","year":2025,"id":510063,"datarank":0.5623204373892683,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0856123628370763,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0856123628370763,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":23,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9637,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04063124","NCT04785300","NCT05362786","NCT04869761","NCT06752577"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":321439,"name":"Gregory S. Day","orcid":"0000-0001-5133-5538","position":1,"is_corresponding":false},{"id":236508,"name":"Sarosh R. Irani","orcid":"0000-0002-7667-9748","position":2,"is_corresponding":false},{"id":230892,"name":"Takahisa Kanekiyo","orcid":"0000-0001-6751-9374","position":3,"is_corresponding":false},{"id":253557,"name":"LaTonya J. Hickson","orcid":"0000-0002-7485-336X","position":4,"is_corresponding":false},{"id":1365336,"name":"Taylor Andrews","orcid":"0000-0003-3363-1549","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T02:47:30.942539Z","pmid":"40009460","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":[]}