Classic dRTA is treated with alkali replacement. If treatment is not instituted early on, however, chronic kidney disease may occur secondary to nephrocalcinosis or uncontrolled nephrolithiasis with consequent obstruction. Of note, alkali treatment does not improve deafness in patients with autosomal recessive disease because orally administered alkali cannot access the inner ear compartment.

Hyperkalemic dRTA is chiefly a by-product of distal nephron dysfunction secondary to aldosterone resistance or deficiency. Acidosis reflects both the absence of aldosterone-induced proton secretion and the inhibitory effects of hyperkalemia on ammoniagenesis.

Most cases are related to drugs or to hyporeninemic hypoaldosteronism. The most commonly implicated drugs include trimethoprim, cyclosporine, and ACE inhibitors. Trimethoprim acts as an antagonist of the ENaC, whereas cyclosporine inhibits the basolateral Na⁺/K⁺ ATPase. Hyporeninemic hypoaldosteronism is most often found in the context of renal insufficiency, especially that caused by diabetes mellitus.

Hyperkalemic dRTA is treated by withdrawing precipitating drugs and providing sodium bicarbonate. Fludrocortisone and/or potassium-lowering drugs, such as oral resins, are also helpful, since reducing serum potassium concentrations increases renal ammoniagenesis and ammonia excretion.

MIXED RTA

The entity of transient mixed proximal/distal RTA arising just after birth is thought to mark a developmental hiatus in distal nephron function, which normally continues to mature after birth. Nontransient RTA with both proximal and distal tubular dysfunction does, however, accompany one form of autosomal recessive osteopetrosis (Guibaud-Vainsel syndrome or marble brain disease). Investigators have identified loss of carbonic anhydrase 2, an enzyme expressed both throughout the nephron and in osteoclasts, as the biochemical defect. The disease presents in infancy, with major signs including thickened but brittle bones, short stature, mental retardation, dental malocclusion, and visual impairment from optic nerve compression. Calcification of the basal ganglia may occur.