Abstract
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.
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.
| Original language | English |
|---|---|
| Article number | N/A |
| Pages (from-to) | 1899-1905 |
| Number of pages | 17 |
| Journal | Journal of the American Society of Nephrology |
| Volume | 8 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 7 Nov 2013 |
