Demystifying normal-anion-gap metabolic acidosis: pathophysiology, aetiology, evaluation and diagnosis

Normal-anion-gap metabolic acidosis (NAGMA) is a common but often under-recognised and poorly understood condition, especially by less-experienced clinicians. In adults, NAGMA might be an initial clue to a more significant underlying pathology, such as autoimmune diseases, hypergammaglobulinemia or drug toxicities. However, identifying the aetiology can be challenging due to the diverse processes involved in the development of acidosis. A better understanding of the pathophysiology of NAGMA can help treating physicians suspect and evaluate the condition early and reach the correct diagnosis. This article provides an overview of renal acid–base regulation, discusses the pathophysiological processes involved in developing NAGMA and provides a framework for evaluation to reach an accurate diagnosis.