{"id":"166592fa-9d3f-5d22-a28a-ab907bf94ef9","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:combined-na-mg-restriction-romk-hypokalemia","predicate":"combined-restriction-with-sodium-increases","statement":"Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"0f06a6c5-a80a-5c03-bfaa-48da25cc2582","mechanism_event_label":"In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.","subject":{"id":"1f0c42f0-eaf3-5b86-966d-7ffc8a84872b","slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"},"object":{"id":"bdc516b4-647c-52b3-9b85-c925a0aec2ce","slug":"kcnj1","display_name":"Renal outer medullary potassium channel / KCNJ1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"0f06a6c5-a80a-5c03-bfaa-48da25cc2582","stable_key":"0f17db03-207f-5910-ac8e-13dfc2f378ce:combined-na-mg-restriction-romk-hypokalemia-event","event_type":"biochemical_relationship","label":"In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.","description":"Combined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"0e4aaa90-5b94-5d69-ba79-d760da4e0268","slug":"sodium","display_name":"Sodium","entity_type_key":"nutrient_element"},"role":"co-restricted nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"5dd31e52-f51e-51f3-880e-240abcc0ab1d","slug":"potassium-ion","display_name":"Potassium ion","entity_type_key":"ion"},"role":"lost ion","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"b6e8049f-ad5c-5ca0-ba73-1d4392131397","slug":"enac","display_name":"Epithelial sodium channel","entity_type_key":"protein_complex"},"role":"preserved sodium entry pathway","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"91de6063-d0ae-5f4c-9935-75bcec18c7b5","slug":"serum-potassium-concentration","display_name":"Serum or plasma potassium concentration","entity_type_key":"cellular_process"},"role":"measured plasma endpoint","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"1f0c42f0-eaf3-5b86-966d-7ffc8a84872b","slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"bdc516b4-647c-52b3-9b85-c925a0aec2ce","slug":"kcnj1","display_name":"Renal outer medullary potassium channel / KCNJ1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"magnesium -> sodium -> potassium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Seven days","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"combination\": \"joint\", \"comparator\": \"Normal diet\", \"conditions\": [{\"entity_slug\": \"sodium\", \"state\": \"Restricted\"}, {\"entity_slug\": \"magnesium\", \"state\": \"Restricted\"}], \"effect_direction\": \"increase\", \"endpoint\": \"Native ROMK activity in DCT2/CNT\", \"intervention\": \"Combined dietary sodium and magnesium restriction\"}","comparator":null,"unit":null,"notes":"Primary abstract PMID 41137719 / DOI 10.1113/JP287704 rechecked 2026-09-20. This comparison must not be separated into two single-deficiency effects.","entity":null},{"dimension":"experimental_model","value_text":"Dietary restriction in C57BL/6J mice with renal transport assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Magnesium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"magnesium","display_name":"Magnesium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Kidney distal nephron","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"4207fca8-5019-5049-9a83-3aaff79475d2","evidence_kind":"source_excerpt","locator":"Lines 178-189","start_line":178,"end_line":189,"excerpt":"### combined-na-mg-restriction-romk-hypokalemia\nCombined Na/Mg restriction increased native ROMK activity in DCT2/CNT and lowered plasma K, while ENaC cleavage markers were preserved relative to normal diet.\nCondition category: nutrient_deficiency\nnutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: In this combined shortage, the Mg-sensitive potassium pathway was more active while the sodium pathway that supports potassium exit remained available.\norganism: Mus musculus\ntissue_or_cell_type: Kidney distal nephron\nexperimental_model: Dietary restriction in C57BL/6J mice with renal transport assays\nlimitations: Co-occurrence supports the proposed mechanism; intracellular Mg and distal Na delivery were not directly measured.\ncross_nutrient: magnesium -> sodium -> potassium\nduration: Seven days\n[maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704","model_system":"Dietary restriction in C57BL/6J mice with renal transport assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [maeoka-2025-enac-romk] Hypomagnesaemia-associated hypokalaemia requires activation of both ENaC and ROMK (2025). https://pubmed.ncbi.nlm.nih.gov/41137719/ DOI: 10.1113/JP287704","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dd101e28-1a2e-5a48-9d1e-809c77514866","stable_key":"import-0f17db03-207f-5910-ac8e-13dfc2f378ce","title":"Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"e111c412f57143a17e8e65e74e8f7888b5bb9a61099873f4767f527fac19bb07","revision_id":"6b7f04f2-66ed-5859-955f-c2b50d4bf041","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}