provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. PMC Copyright notice PMCID: PMC10747299  PMID: 38144560 Abstract The Syndrome of Inappropriate ADH secretion (SIADH) presents with excess ADH release caused by a range of conditions; including pneumonia, brain tumors, certain lung cancers, and diseases of the hypothalamus. It presents with significant reduction in both sodium and chloride concentrations in the blood. However, reports examining the acid base status indicate a normal serum bicarbonate concentration and systemic acid base homeostasis. The mechanisms for the absence of abnormalities in acid base homeostasis remain speculative. This mini review is highlighting the recent advances in renal molecular physiology to provide answers for the maintenance of acid base status and serum bicarbonate in a physiological range. Keywords: SIADH, hyponatremia, acid base balance, bicarbonate, collecting duct, AVPR1a, intercalated cells, H + -ATPase 1. Introduction The Syndrome of Inappropriate Anti-Diuretic Hormone secretion (SIADH) is a frequent clinical encounter with significant morbidity and mortality in hospital admissions. At its core, this disorder presents with excess ADH due to the inability of the body to suppress its secretion. It is caused by a range of conditions, including pneumonia, brain tumors, certain lung cancers, and diseases of the hypothalamus ( 1 – 3 ). There are hardly any studies examining the mechanism of acid base homeostasis in SIADH despite the significant reduction in both sodium and chloride concentrations in the blood. All reports refer to normal serum bicarbonate levels and by inference a balanced acid base status in SIADH. In this short commentary, we have discussed the physiological and molecular pathways that may be playi