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.