distal renal tubular acidosis

Distal RTA results from dysfunction of the α-intercalated cells in the collecting duct, which normally secrete H+ via H+-ATPase and H+/K+-ATPase pumps, and regenerate bicarbonate via the Cl-/HCO3- exchanger (AE1/band 3 protein). Defects can be inherited (mutations in ATP6V1B1, ATP6V0A4, or SLC4A1/AE1 genes) or acquired (autoimmune diseases like Sjögren syndrome and SLE, amphotericin B toxicity, obstructive uropathy, sickle cell disease). Because H+ secretion is impaired, urine pH remains inappropriately high (>5.5) even in the setting of systemic acidosis—this is the key distinguishing feature from proximal RTA (Type 2), where distal acidification is intact and urine can become acidic. The chronic acidosis causes bone buffering (release of calcium and phosphate from bone), leading to hypercalciuria and hypocitraturia (citrate is reabsorbed more avidly in acidosis), which together with alkaline urine promotes calcium phosphate stone formation and nephrocalcinosis. Hypokalemia occurs due to increased aldosterone-driven K+ secretion (as a compensatory mechanism when H+ secretion fails, the Na+/K+ exchange pathway becomes favored) and can lead to muscle weakness. Distal RTA is also associated with osteomalacia/rickets in children due to chronic acidosis affecting bone mineralization, and growth failure. Diagnosis involves confirming non-anion gap metabolic acidosis, urine pH >5.5 despite acidemia, and can be confirmed with an ammonium chloride loading test (failure to acidify urine below pH 5.5) or urine anion gap (which will be more positive, unlike GI losses of bicarbonate which show a negative urine anion gap). Treatment involves oral bicarbonate or citrate supplementation to correct acidosis, replace potassium, and prevent stone formation and bone disease. Contrast with Type 4 RTA (hypoaldosteronism), which causes hyperkalemia rather than hypokalemia, and Type 2 (proximal) RTA, which involves defective HCO3- reabsorption in the proximal tubule and is associated with Fanconi syndrome.