Diagnostic Evaluation of Renal Tubular Acidosis: A Clinical Biochemistry Perspective

Tight regulation of plasma pH is critical for cellular homeostasis. Physiological pH is maintained through a complex synergy of buffering, pulmonary modulation of carbon dioxide concentration, and regulation of systemic bicarbonate by the renal system. Renal tubular acidosis (RTA) describes a group of disorders in which the tubular excretion of acid is reduced despite relatively normal glomerular filtration. Several subtypes of RTA are known, all of which classically present with normal anion gap metabolic acidosis in addition to a variety of associated biochemical abnormalities. RTA can pose a diagnostic challenge to the clinician as it can be triggered by a substantial number of different aetiologies and clinical presentations can be highly variable. This review addresses the normal renal handling of acid-base, the renal response to high acid load, and the RTA pathologies where these acid-base homeostatic mechanisms are impaired. A particular focus of this review is the challenges faced by the biochemical laboratory regarding the development, validation and interpretation of suitable plasma and urine tests for accurate RTA diagnosis.