{"id":"c579538e-d837-5eb9-ad53-f492a9f7794d","stable_key":"b7798a90-72a3-5454-a321-c4be88bf0cc4:lithium-amiloride-human","predicate":"improves","statement":"Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"0377089f-d718-55ce-8e50-ffbda97bfd13","mechanism_event_label":"Blocking a sodium channel improved the measured water response.","subject":{"id":"78506253-1833-5641-89d3-c07bcfcc73a9","slug":"amiloride","display_name":"Amiloride","entity_type_key":"small_molecule"},"object":{"id":"40d861d6-c873-5a0b-9786-acd40cad5f97","slug":"human-lithium-urine-concentration","display_name":"Human urine-concentrating response during lithium treatment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"0377089f-d718-55ce-8e50-ffbda97bfd13","stable_key":"b7798a90-72a3-5454-a321-c4be88bf0cc4:lithium-amiloride-human-event","event_type":"observed_relationship","label":"Blocking a sodium channel improved the measured water response.","description":"Amiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"78506253-1833-5641-89d3-c07bcfcc73a9","slug":"amiloride","display_name":"Amiloride","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"40d861d6-c873-5a0b-9786-acd40cad5f97","slug":"human-lithium-urine-concentration","display_name":"Human urine-concentrating response during lithium treatment","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8e2e3902-5e26-52e3-9c85-1d7c0ace1637","slug":"lithium","display_name":"Lithium","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"13b4b09c-4581-58f6-9792-9a78125963e8","slug":"lithium-ion","display_name":"Lithium ion (Li+)","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"0cf1432e-2f5f-542c-8980-6894da46cce6","slug":"aqp2","display_name":"Aquaporin-2 / AQP2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"38de8704-84db-5770-ac1d-242cd787e798","slug":"sodium-ion","display_name":"Sodium ion","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized placebo-controlled crossover; six-week periods.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lithium","display_name":"Lithium","entity_type_key":"nutrient_element"}},{"dimension":"plain_language","value_text":"Blocking a sodium channel improved the measured water response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"631609e6-ee37-5ab5-8857-05547a2fc87f","evidence_kind":"source_excerpt","locator":"Lines 344-350","start_line":344,"end_line":350,"excerpt":"## lithium-amiloride-human\nBlocking a sodium channel improved the measured water response.\nAmiloride increased maximal urine osmolality and AQP2 excretion in an eleven-patient crossover trial during lithium therapy.\nModel: Randomized placebo-controlled crossover; six-week periods.\nLimitations: Small trial; reduced lithium entry was inferred, not directly measured in patient kidney cells.\nEvidence access: Primary abstract\nLithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18596116/ · DOI 10.2215/CJN.01640408","model_system":"Randomized placebo-controlled crossover; six-week periods.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b2dd2f3c-5c4c-5a12-9a0d-91b521ffcf98","stable_key":"import-b7798a90-72a3-5454-a321-c4be88bf0cc4","title":"Lithium: metal-sensitive enzymes, transport and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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