{"doi":"10.1016/j.celrep.2022.111840","title":"Kir4.2 mediates proximal potassium effects on glutaminase activity and kidney injury","abstract":"Inadequate potassium (K + ) consumption correlates with increased mortality and poor cardiovascular outcomes. Potassium effects on blood pressure have been described previously; however, whether or not low K + independently affects kidney disease progression remains unclear. Here, we demonstrate that dietary K + deficiency causes direct kidney injury. Effects depend on reduced blood K + and are kidney specific. In response to reduced K + , the channel Kir4.2 mediates altered proximal tubule (PT) basolateral K + flux, causing intracellular acidosis and activation of the enzyme glutaminase and the ammoniagenesis pathway. Deletion of either Kir4.2 or glutaminase protects from low-K + injury. Reduced K + also mediates injury and fibrosis in a model of aldosteronism. These results demonstrate that the PT epithelium, like the distal nephron, is K + sensitive, with reduced blood K + causing direct PT injury. Kir4.2 and glutaminase are essential mediators of this injury process, and we identify their potential for future targeting in the treatment of chronic kidney disease.","journal":"Cell Reports","year":2022,"id":253966,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.953,"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":901154,"name":"Yahua Zhang","orcid":null,"position":1,"is_corresponding":false},{"id":777438,"name":"Juan Pablo Arroyo","orcid":"0000-0002-5992-5011","position":2,"is_corresponding":false},{"id":648522,"name":"Shirong Cao","orcid":"0000-0002-6593-4600","position":3,"is_corresponding":false},{"id":448125,"name":"Suwan Wang","orcid":null,"position":4,"is_corresponding":false},{"id":521075,"name":"Xiaofeng Fan","orcid":"0000-0002-3201-5499","position":5,"is_corresponding":false},{"id":328000,"name":"Jerod S. Denton","orcid":"0000-0003-0032-8586","position":6,"is_corresponding":false},{"id":448126,"name":"Ming‐Zhi Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":340027,"name":"Raymond C. Harris","orcid":"0000-0001-8025-0883","position":8,"is_corresponding":false},{"id":648519,"name":"Andrew S. Terker","orcid":"0000-0003-1498-9043","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T00:25:03.918844Z","pmid":"36543132","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":[]}