Chapter 11 - Proximal Renal Tubular Acidosis

Abstract

Proximal renal tubular acidosis (pRTA) is a disease of defective proximal tubule function resulting in metabolic acidosis. This chapter will review the transport processes for acid-base equivalents in the proximal tubule, the clinical features of pRTA, and the specific molecular defects that can give rise to pRTA. Two mechanisms contribute to bicarbonate exit across the basolateral membrane of proximal tubule cells, namely Na+ -HCO3¯ cotransport and Cl¯ -HCO3¯ exchange. Na+ -HCO3¯ cotransport is the predominant mechanism through most of the length of the proximal tubule (S1 and S2), whereas Cl¯-CO3¯ is important in the S3 segment. A Na+:HCO3¯ stoichiometry of 1:3 is required for the transporter to mediate net HCO3 efflux across the basolateral membrane of proximal tubule cells. Therefore, a regulatory change in stoichiometry from 1:3 to 1:2 would be expected to change the net direction of transport from outward to inward across the basolateral membrane and thereby impede net bicarbonate reabsorption. The pRTA is defined as a hyperchloremic metabolic acidosis due to a defect in bicarbonate transport capacity in the nephron segment. In a patient with pRTA there is a greatly reduced threshold of plasma bicarbonate at which bicarbonate appears in the urine, and the maximal rate of reabsorption of bicarbonate is markedly depressed. The principal cause of isolated pRTA is a defect in basolateral base exit that would be predicted to lead to relative alkalinization of intracellular pH in proximal tubule cells. Such intracellular alkalinization would tend to mitigate the effects of systemic acidosis and thereby maintain citrate excretion at a higher level than observed in distal RTA (dRTA).