New insights into the pathogenesis of distal renal tubular acidosis

The diagnosis and classification of distal renal tubular acidosis (distal RTA) have traditionally been made on the basis of the renal response to physiologic maneuvers, providing only indirect information on the underlying pathophysiology. In the past several years significant advances have been made in our understanding of the molecular basis of distal H+/HCO3- secretion and absorption, at the level of individual transporters. With these advances, a new era of classifying disorders of distal acidification at the molecular level has arrived. In this article we review the cellular and molecular basis of normal acidification mechanisms in the distal nephron. We also review the recent information on the molecular basis of derangements in these mechanisms which lead to distal RTA.