{"doi":"10.1093/ndt/gfac214","title":"The modifying effect of the serum-to-dialysate potassium gradient on the cardiovascular safety of SSRIs in the hemodialysis population: a pharmacoepidemiologic study","abstract":"BACKGROUND: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). METHODS: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study. RESULTS: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results. CONCLUSIONS: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.","journal":"Nephrology Dialysis Transplantation","year":2022,"id":276751,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":432207,"name":"Patrick H. Pun","orcid":"0000-0002-9896-8292","position":1,"is_corresponding":false},{"id":337350,"name":"Sana M. Al‐Khatib","orcid":"0000-0002-3561-0146","position":2,"is_corresponding":false},{"id":540857,"name":"M. Alan Brookhart","orcid":"0000-0003-1572-0564","position":3,"is_corresponding":false},{"id":366445,"name":"Bradley N. Gaynes","orcid":"0000-0002-8283-5030","position":4,"is_corresponding":false},{"id":109012,"name":"Wolfgang C. Winkelmayer­","orcid":"0000-0002-5272-425X","position":5,"is_corresponding":false},{"id":241192,"name":"Jennifer E. Flythe","orcid":"0000-0003-4596-8536","position":6,"is_corresponding":false},{"id":243737,"name":"Magdalene M. Assimon","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:28:30.709588Z","pmid":"35793567","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":[]}