title: Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients.
abstract: BACKGROUND
  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).
  
  
  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.
authors: Diabetes Centre, Khoo Teck Puat Hospital, Republic of Singapore lim.su.chi@alexandrahealth.com.sg.
authors: Su Chi
authors: SC
authors: Lim
authors: Clinical Research Unit, Khoo Teck Puat Hospital, Republic of Singapore.
authors: Jian-Jun
authors: JJ
authors: Liu
authors: Diabetes Centre, Khoo Teck Puat Hospital, Republic of Singapore.
authors: Tavintharan
authors: T
authors: Subramaniam
authors: Diabetes Centre, Khoo Teck Puat Hospital, Republic of Singapore.
authors: Chee Fang
authors: CF
authors: Sum
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077583:Quinapril; D044005:Tetrahydroisoquinolines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044005:Tetrahydroisoquinolines; D005966:Glucuronidase; D000090265:Klotho Proteins; D019808:Losartan; D000077583:Quinapril
keywords: angiotensin receptor 1 blocker; diabetes; losartan; α-klotho