New Findings on the Pathogenesis of Distal Renal Tubular Acidosis.

Background: Distal renal tubular acidosis (dRTA) is characterized by an impairment of the urinary acidification process in the distal nephron. Complete or incomplete metabolic acidosis coupled with inappropriately alkaline urine are the hallmarks of this condition. Genetic forms of dRTA are caused by loss of function mutations of either SLC4A1 , encoding the AE1 anion exchanger, or ATP6V1B1 and ATP6V0A4 , encoding for the B1 and a4 subunits of the vH+ ATPase, respectively. These genes are crucial for the function of A-type intercalated cells (A-IC) of the distal nephron.

Summary: Alterations of acid-base homeostasis are variably associated with hypokalemia, hypercalciuria, nephrocalcinosis or nephrolithiasis, and a salt-losing phenotype. Here we report the diagnostic test and the underlying physiopathological mechanisms. The molecular mechanisms identified so far can explain the defect in acid secretion, but do not explain all clinical features. We review the latest experimental findings on the pathogenesis of dRTA, reporting mechanisms that are instrumental for the clinician and potentially inspiring a novel therapeutic strategy.

Key Message: Primary dRTA is usually intended as a single-cell disease because the A-IC are mainly affected. However, novel evidence shows that different cell types of the nephron may contribute to the signs and symptoms, moving the focus from a single-cell towards a renal disease.