Angiotensin II receptors mediate increased distal nephron acidification caused by acid retention

Kidney Int. 2012 Dec;82(11):1184-94. doi: 10.1038/ki.2012.267. Epub 2012 Jul 25.


Patients with a moderately reduced glomerular filtration rate (GFR) typically have no metabolic acidosis and a urine net acid excretion comparable to those with normal GFR, supporting greater per nephron acidification with moderately reduced GFR. We modeled such patients using rats with a surgical reduction of 2/3 kidney mass, yielding animals with reduced GFR without metabolic acidosis. We then tested the hypothesis that reduction of nephron mass augments distal nephron acidification in remnant nephrons mediated by increased angiotensin II activity, and that the latter is induced by underlying acid retention. Nephron mass reduction yielded lower GFR than controls (sham operation), higher acid retention (measured by microdialysis of kidney cortex), higher distal nephron acidification, and higher plasma and kidney levels of angiotensin II, but plasma total CO(2) and urine net acid excretion were not different. Angiotensin II receptor antagonism reduced distal nephron acidification to levels similar to control. Dietary alkali that lowered acid retention to that of control also reduced plasma and kidney levels of angiotensin II and reduced distal nephron acidification to control. Angiotensin II receptor antagonism with dietary alkali had no significant added effect on distal nephron acidification. Thus, nephron reduction that moderately reduced GFR with no metabolic acidosis is characterized by increased angiotensin II activity. This mediates increased distal nephron acidification and is induced by acid retention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Acidosis, Renal Tubular / etiology
  • Acidosis, Renal Tubular / metabolism*
  • Aldosterone / blood
  • Angiotensin II / blood
  • Angiotensin Receptor Antagonists
  • Animals
  • Endothelin Receptor Antagonists
  • Endothelins / blood
  • Female
  • Glomerular Filtration Rate
  • Kidney Tubules, Distal / metabolism*
  • Male
  • Microdialysis
  • Mineralocorticoid Receptor Antagonists
  • Nephrectomy
  • Protons*
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Receptors, Endothelin / metabolism
  • Receptors, Mineralocorticoid / metabolism
  • Renal Insufficiency / complications
  • Renal Insufficiency / metabolism*


  • Angiotensin Receptor Antagonists
  • Endothelin Receptor Antagonists
  • Endothelins
  • Mineralocorticoid Receptor Antagonists
  • Protons
  • Receptor, Angiotensin, Type 2
  • Receptors, Endothelin
  • Receptors, Mineralocorticoid
  • Angiotensin II
  • Aldosterone