Pathogenesis of distal renal tubular acidosis

Distal renal tubular acidosis (RTA) is a syndrome characterized by hyperchloremic metabolic acidosis and an inappropriately high urine pH relative to the degree of acidosis. The clinical presentation is frequently complicated by nephrocalcinosis, hypercalciuria, and nephrolithiasis. Less frequent presenting manifestations include hypokalemia and osteomalacia (for review of clinical features, see Refs. 1–4). Initially, all cases of renal tubular acidosis were considered to have similar pathophysiologic mechanisms, but subsequent studies have subdivided the group into abnormalities of bicarbonate reabsorption (proximal RTA), disorders of net acid excretion (distal or classical), and defects of ammonium production. In the present review, we will limit our discussion to the pathogenesis of distal RTA.