| Summary: | Background: Soluble Klotho is an anti-ageing phosphaturic protein associated with cardiovascular and renal protection. In-vitro and in-vivo studies have demonstrated that rennin-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.
Methods and measurements: Plasma soluble Klotho was measured in a secondary analysis of a randomised controlled clinical trial performed at a single university centre. Seventy-six patients with Type-2 diabetes, and DKD (all with albuminuria and serum creatinine <1.7mg/dl) were studied at baseline and at 24-weeks (end of study), following randomisation to valsartan/hydrochlorothiazide (n=37) or amlodipine (n=39) treatment. Aortic-pulse wave velocity (Ao-PWV) by applanation tonometry and albuminuria (from 3-timed urine collections) were also measured at baseline and 24-weeks.
Results: Valsartan/hydrochlorothiazide treatment significantly increased soluble Klotho mean±standard deviation, from 432.7±179 to 506.4±226.8 pg/ml, p=0.01 and reduced serum phosphate 3.25±1.18 to 2.60±0.96 mg/dl, p=0.04 compared to amlodipine (430.1±145.8 to 411.9±157.6 pg/ml and 2.94±0.56 to 2.69±1.52 mg/dl]. There was a significant between treatment group difference, mean (95% confidence interval), in soluble Klotho, 91.9 (19.9 to 162) pg/ml and serum phosphate levels −0.68 (−0.15 to −1.33) mg/dl with valsartan/hydrochlorothiazide treatment, p=0.04 for both. Attained blood pressure was similar in the two groups and levels of soluble Klotho were not associated with Ao-PWV and albuminuria, variables which 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 blood pressure independent cardio-renal benefits of these drugs in DKD.
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