Angiotensin II-mediated GFR decline in subtotal nephrectomy is due to acid retention associated with reduced GFR

Nephrol Dial Transplant. 2015 May;30(5):762-70. doi: 10.1093/ndt/gfu388. Epub 2014 Dec 19.


Background: Angiotensin II (AII) mediates glomerular filtration rate (GFR) decline in animals with subtotal nephrectomy (Nx), but the mechanisms for increased AII activity are unknown. Because reduced GFR of Nx is associated with acid (H(+)) retention that increases kidney AII, AII-mediated GFR decline might be induced by H(+) retention.

Methods: We measured GFR and kidney microdialyzate H(+) and AII content in Sham and 2/3 Nx rats in response to amelioration of H(+) retention with dietary NaHCO3, to AII receptor antagonism and to both.

Results: GFR was lower in Nx than that in Sham. Nx but not Sham GFR was lower at Week 24 than that at Week 1. Despite no differences in plasma acid-base parameters or urine net acid excretion, kidney H(+) content was higher in Nx than that in Sham, consistent with H(+) retention. Plasma and kidney microdialyzate AII were higher in Nx than that in Sham and dietary NaHCO3 reduced each in Nx but not in Sham. AII receptor antagonism was associated with higher Week 24 GFR in Nx with H(+) retention but not in Sham or in Nx in which H(+) retention had been corrected with dietary NaHCO3. Week 24 GFR after dietary NaHCO3 was higher than after AII receptor antagonism. Week 24 GFR was not different after adding AII receptor antagonism to dietary NaHCO3.

Conclusions: AII-mediated GFR decline in 2/3 Nx was induced by H(+) retention and its amelioration with dietary HCO3 conserved GFR better than AII receptor antagonism in this CKD model. H(+) retention might induce AII-mediated GFR decline in patients with reduced GFR, even without metabolic acidosis.

Keywords: aldosterone; angiotensin II; bicarbonate; chronic kidney disease; endothelin; microdialysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Animal Feed
  • Animals
  • Disease Models, Animal
  • Female
  • Glomerular Filtration Rate*
  • Kidney / metabolism
  • Male
  • Microdialysis
  • Nephrectomy / methods*
  • Protons
  • Rats
  • Rats, Wistar
  • Sodium Bicarbonate / metabolism
  • Tetrazoles / administration & dosage
  • Valine / administration & dosage
  • Valine / analogs & derivatives
  • Valsartan


  • Angiotensin II Type 1 Receptor Blockers
  • Protons
  • Tetrazoles
  • Angiotensin II
  • Valsartan
  • Sodium Bicarbonate
  • Valine