Urinary angiotensin-converting enzyme 2 increases in diabetic nephropathy by angiotensin II type 1 receptor blocker olmesartan

J Renin Angiotensin Aldosterone Syst. 2015 Mar;16(1):159-64. doi: 10.1177/1470320314551443. Epub 2014 Oct 6.


Introduction: Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotensin system that degrades angiotensin (Ang) II to the seven-amino acid peptide fragment Ang-(1-7). We evaluated the changes in urinary ACE2 levels in response to treatment with the angiotensin II type 1 receptor blocker olmesartan in diabetes patients with nephropathy.

Materials and methods: This prospective, open-label, interventional study was conducted with 31 type 2 diabetes patients with nephropathy. After initial evaluation, patients received 20 mg/day olmesartan, which was increased to 40 mg/day over a 24-week period.

Results: In diabetes patients with chronic kidney disease, olmesartan significantly increased urinary ACE2 levels independently of blood pressure and plasma aldosterone levels and reduced albuminuria, urinary liver-type fatty acid binding protein (L-FABP), and plasma aldosterone levels. Multivariable regression analysis revealed that the change in urinary L-FABP levels was an independent predictor of increased urinary ACE2 levels.

Conclusion: Olmesartan may have the unique effect of increasing urinary ACE2 levels. However, whether this contributes to olmesartan's renoprotective effect must be examined further.

Keywords: Angiotensin-converting enzyme 2; angiotensin II type 1 receptor blocker; chronic kidney disease; diabetic nephropathy; olmesartan.

MeSH terms

  • Aged
  • Aldosterone / blood
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme 2
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / urine*
  • Female
  • Heart Rate / drug effects
  • Humans
  • Imidazoles / therapeutic use*
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / urine*
  • Prospective Studies
  • Renin / blood
  • Tetrazoles / therapeutic use*


  • Angiotensin II Type 1 Receptor Blockers
  • Imidazoles
  • Tetrazoles
  • Aldosterone
  • olmesartan
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Renin