The multiple roles of pendrin in the kidney

Nephrol Dial Transplant. 2015 Aug;30(8):1257-66. doi: 10.1093/ndt/gfu307. Epub 2014 Oct 3.


The [Formula: see text] exchanger pendrin (SLC26A4, PDS) is located on the apical membrane of B-intercalated cells in the kidney cortical collecting duct and the connecting tubules and mediates the secretion of bicarbonate and the reabsorption of chloride. Given its dual function of bicarbonate secretion and chloride reabsorption in the distal tubules, it was thought that pendrin plays important roles in systemic acid-base balance and electrolyte and vascular volume homeostasis under basal conditions. Mice with the genetic deletion of pendrin or humans with inactivating mutations in PDS gene, however, do not display excessive salt and fluid wasting or altered blood pressure under baseline conditions. Very recent reports have unmasked the basis of incongruity between the mild phenotype in mutant mice and the role of pendrin as an important player in salt reabsorption in the distal tubule. These studies demonstrate that pendrin and the Na-Cl cotransporter (NCC; SLC12A3) cross compensate for the loss of each other, therefore masking the role that each transporter plays in salt reabsorption under baseline conditions. In addition, pendrin regulates calcium reabsorption in the distal tubules. Furthermore, combined deletion of pendrin and NCC not only causes severe volume depletion but also results in profound calcium wasting and luminal calcification in medullary collecting ducts. Based on studies in pathophysiological states and the examination of genetically engineered mouse models, the evolving picture points to important roles for pendrin (SLC26A4) in kidney physiology and in disease states. This review summarizes recent advances in the characterization of pendrin and the multiple roles it plays in the kidney, with emphasis on its essential roles in several diverse physiological processes, including chloride homeostasis, vascular volume and blood pressure regulation, calcium excretion and kidney stone formation.

Keywords: hypertension; oxalate stone; renal tubular acidosis; salt excretion; volume depletion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acid-Base Equilibrium
  • Animals
  • Anion Transport Proteins / physiology*
  • Humans
  • Kidney Diseases / physiopathology*
  • Membrane Transport Proteins / physiology*
  • Mice
  • Solute Carrier Family 12, Member 3 / metabolism
  • Sulfate Transporters
  • Water-Electrolyte Balance


  • Anion Transport Proteins
  • Membrane Transport Proteins
  • SLC12A3 protein, human
  • SLC26A4 protein, human
  • Slc12a3 protein, mouse
  • Slc26a4 protein, mouse
  • Solute Carrier Family 12, Member 3
  • Sulfate Transporters