BACKGROUND AND OBJECTIVES:Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma-soluble Klotho was measured in a secondary analysis of a randomized controlled clinical trial performed at a single university hospital center (ClinicalTrials.gov number NCT001715, from March 2003 to September 2006). Seventy-six patients with type 2 diabetes and DKD (all with albuminuria and serum creatinine <1.7 mg/dl) were studied at baseline and at 24 weeks (study end) after randomization to valsartan/hydrochlorothiazide (n=37) or amlodipine (n=39) treatment. Aortic-pulse wave velocity by applanation tonometry and albuminuria (from three timed urine collections) were also measured at baseline and 24 weeks. RESULTS:Valsartan/hydrochlorothiazide treatment significantly increased mean (± SD) soluble Klotho (from 432.7 ± 179 to 506.4 ± 226.8 pg/ml; P=0.01) and reduced serum phosphate (from 3.25 ± 1.18 to 2.60 ± 0.96 mg/dl; P=0.04) compared with amlodipine (from 430.1 ± 145.8 to 411.9 ± 157.6 pg/ml and from 2.94 ± 0.56 to 2.69 ± 1.52 mg/dl, respectively). There was a significant difference between treatment groups in soluble Klotho (mean 91.9 pg/ml; 95% confidence interval, 19.9 to 162) and serum phosphate levels (mean -0.68 mg/dl; 95% confidence interval, -0.15 to -1.33) with valsartan/hydrochlorothiazide treatment (P=0.03 and P=0.04, respectively). Attained BP was similar in the two groups and levels of soluble Klotho were not associated with aortic-pulse wave velocity and albuminuria, variables that fell significantly only with valsartan/hydrochlorothiazide. CONCLUSIONS: Treatment with a RAS blocker, valsartan, is associated with an increase in soluble Klotho, which may contribute to the BP-independent cardiorenal benefits of these drugs in DKD.
RCT Entities:
BACKGROUND AND OBJECTIVES: Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma-soluble Klotho was measured in a secondary analysis of a randomized controlled clinical trial performed at a single university hospital center (ClinicalTrials.gov number NCT001715, from March 2003 to September 2006). Seventy-six patients with type 2 diabetes and DKD (all with albuminuria and serum creatinine <1.7 mg/dl) were studied at baseline and at 24 weeks (study end) after randomization to valsartan/hydrochlorothiazide (n=37) or amlodipine (n=39) treatment. Aortic-pulse wave velocity by applanation tonometry and albuminuria (from three timed urine collections) were also measured at baseline and 24 weeks. RESULTS:Valsartan/hydrochlorothiazide treatment significantly increased mean (± SD) soluble Klotho (from 432.7 ± 179 to 506.4 ± 226.8 pg/ml; P=0.01) and reduced serum phosphate (from 3.25 ± 1.18 to 2.60 ± 0.96 mg/dl; P=0.04) compared with amlodipine (from 430.1 ± 145.8 to 411.9 ± 157.6 pg/ml and from 2.94 ± 0.56 to 2.69 ± 1.52 mg/dl, respectively). There was a significant difference between treatment groups in soluble Klotho (mean 91.9 pg/ml; 95% confidence interval, 19.9 to 162) and serum phosphate levels (mean -0.68 mg/dl; 95% confidence interval, -0.15 to -1.33) with valsartan/hydrochlorothiazide treatment (P=0.03 and P=0.04, respectively). Attained BP was similar in the two groups and levels of soluble Klotho were not associated with aortic-pulse wave velocity and albuminuria, variables that fell significantly only with valsartan/hydrochlorothiazide. CONCLUSIONS: Treatment with a RAS blocker, valsartan, is associated with an increase in soluble Klotho, which may contribute to the BP-independent cardiorenal benefits of these drugs in DKD.
Authors: M J Kool; F A Lustermans; J G Breed; H A Struyker Boudier; A P Hoeks; R S Reneman; L M Van Bortel Journal: J Hypertens Date: 1995-08 Impact factor: 4.844
Authors: Brian A Bergmark; Jacob A Udell; David A Morrow; Petr Jarolim; Julia F Kuder; Scott D Solomon; Marc A Pfeffer; Eugene Braunwald; Marc S Sabatine Journal: Eur J Heart Fail Date: 2019-02-18 Impact factor: 15.534
Authors: Rukshana Shroff; Helen Aitkenhead; Nikola Costa; Antonella Trivelli; Mieczyslaw Litwin; Stefano Picca; Ali Anarat; Peter Sallay; Fatih Ozaltin; Aleksandra Zurowska; Augustina Jankauskiene; Giovanni Montini; Marina Charbit; Franz Schaefer; Elke Wühl Journal: J Am Soc Nephrol Date: 2015-06-11 Impact factor: 10.121