In addition to acidosis, pRTA features hypokalemia because the nonreabsorbed bicarbonate produces a negative charge in the collecting duct lumen, promoting K⁺ secretion through ROM-K channels. If there is generalized proximal tubule dysfunction, the increased distal Na⁺ load that reaches the cortical collecting duct also produces a negative intraluminal charge as it is reabsorbed. In addition, the increased urine flow through the distal tubule, which results from proximal salt wasting, stimulates K⁺ secretion through flow-sensitive maxi-K channels.

Although acidosis and hypokalemia are the hallmarks of pRTA, several additional abnormalities are often seen. Patients with generalized proximal tubular dysfunction, for example, exhibit salt wasting, polyuria, phosphaturia (and hypophosphatemia), glucosuria, uricosuria (and hypouricemia), aminoaciduria, microalbuminuria, and low molecular weight proteinuria (e.g., retinol binding protein or P₂-microglobulin). Moreover, patients often develop rickets or osteomalacia (depending on age) because of inefficient renal activation of vitamin D. Meanwhile, patients with isolated pRTA, like those with NBC transporter mutations, often have aberrant calcification within the eyes (band keratopathy), cataracts, and mental retardation.

Proximal RTA is often difficult to treat because the marked bicarbonaturia mandates that large quantities of alkali be provided on a regular basis. Extensive bicarbonate supplementation, however, often causes worsening hypokalemia, and thus potassium supplements are often required as well. If there is generalized proximal tubular dysfunction, vitamin D and phosphate supplements are also helpful.

DISTAL RTA

The collecting duct contains principal cells and intercalated cells (ICs), with the latter responsible for acidbase handling. Within the IC population, at least two subtypes of cells have been described: type A and type B. Type A cells secrete protons and reabsorb bicarbonate, whereas type B cells do the reverse. It is unclear if type A and B cells are molecular mirror images or separate cell types; however, the acid load in the average human diet dictates that the great majority of ICs be type A.