Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

J Renin Angiotensin Aldosterone Syst. 2014 Dec;15(4):487-90. doi: 10.1177/1470320313475905. Epub 2013 Feb 4.


Introduction: The aging-suppression gene α-klotho is potentially reno-protective. Animal studies suggest that angiotensin II may be a negative regulator of α-klotho expression. Therefore, we hypothesize that renin-angiotensin system antagonism may increase α-klotho secretion in type 2 diabetes (T2DM).

Subjects and methods: In this post-hoc analysis of a randomized crossover study, 33 T2DM subjects with albuminuria received either 50 mg of losartan or 20 mg of quinapril (both 50% maximal dose) daily for 4 weeks with 4-week wash-out period in between.

Results: Our data showed that losartan, but not quinapril, significantly increased circulating α-klotho level by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Linear regression revealed that, besides different mode of treatment, increment in plasma α-klotho was associated with decrement in urine albumin/creatinine ratio (β=-0.263, p=0.029).

Conclusions: The angiotensin receptor blocker losartan increases circulating α-klotho in T2DM with albuminuria. The clinical significance of this rise in α-klotho associated with losartan intervention deserves further investigation.

Keywords: angiotensin receptor 1 blocker; diabetes; losartan; α-klotho.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / blood
  • Albuminuria / complications*
  • Albuminuria / drug therapy*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Glucuronidase / blood*
  • Humans
  • Losartan / pharmacology
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Quinapril
  • Tetrahydroisoquinolines / pharmacology
  • Tetrahydroisoquinolines / therapeutic use


  • Angiotensin II Type 1 Receptor Blockers
  • Tetrahydroisoquinolines
  • Glucuronidase
  • klotho protein
  • Losartan
  • Quinapril