Acid-base transport by the renal proximal tubule

J Am Soc Nephrol. 2006 Sep;17(9):2368-82. doi: 10.1681/ASN.2006060620. Epub 2006 Aug 16.


One of the major tasks of the renal proximal tubule is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered HCO3- as well as generating new HCO3- for regulating blood pH. This review summarizes the cellular and molecular events that underlie four major processes in HCO3- reabsorption. The first is CO2 entry across the apical membrane, which in large part occurs via a gas channel (aquaporin 1) and acidifies the cell. The second process is apical H+ secretion via Na-H exchange and H+ pumping, processes that can be studied using the NH4+ prepulse technique. The third process is the basolateral exit of HCO3- via the electrogenic Na/HCO3 co-transporter, which is the subject of at least 10 mutations that cause severe proximal renal tubule acidosis in humans. The final process is the regulation of overall HCO3- reabsorption by CO2 and HCO3- sensors at the basolateral membrane. Together, these processes ensure that the proximal tubule responds appropriately to acute acid-base disturbances and thereby contributes to the regulation of blood pH.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acid-Base Equilibrium / physiology*
  • Ammonia / metabolism
  • Angiotensin II / physiology
  • Animals
  • Aquaporin 1 / physiology
  • Bicarbonates / metabolism
  • Carbon Dioxide / metabolism
  • Humans
  • Kidney Tubules, Proximal / physiology*
  • Protein-Tyrosine Kinases / physiology
  • Sodium-Bicarbonate Symporters / genetics
  • Sodium-Bicarbonate Symporters / physiology


  • Bicarbonates
  • SLC4A4 protein, human
  • Sodium-Bicarbonate Symporters
  • Angiotensin II
  • Carbon Dioxide
  • Aquaporin 1
  • Ammonia
  • Protein-Tyrosine Kinases