Purpose of review: Research in the past several years has led to the understanding of numerous genetic mutations that lead to inheritable forms of distal renal tubular acidosis (dRTA). Most of these mutations affect the physiology of the A-intercalated cells of the renal cortical collecting duct. These include mutations of genes encoding carbonic anhydrase II, kidney anion exchanger 1, and different subunits of the H+-ATPase proton pump. Genetic defects in any one of these components may impair renal acidification and thereby result in persistent acidosis, failure to thrive, and nephrocalcinosis.
Recent findings: The present review provides a summary of the most recently identified genetic mutations resulting in a dRTA phenotype and, when possible, describes a mechanism. Most causes of dRTA are due to loss of function or inappropriate targeting of transporters.
Summary: The collaboration of clinicians, geneticists, and renal physiologists has enabled us to better understand at the cellular level the different mechanisms leading to dRTA. Such information should lead to earlier diagnosis and treatment, thereby minimizing the irreversible complications affecting patients with this or similar diseases.