{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:16:05Z","timestamp":1791483365851,"version":"4.3.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11]]},"abstract":"Summary<\/jats:title>\n \n Background and objectives<\/jats:title>\n \n Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection.\n In vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n 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 n<\/jats:italic>\n =37) or amlodipine (\n n<\/jats:italic>\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.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Valsartan\/hydrochlorothiazide treatment significantly increased mean (\u00b1 SD) soluble Klotho (from 432.7\u00b1179 to 506.4\u00b1226.8 pg\/ml;\n P<\/jats:italic>\n =0.01) and reduced serum phosphate (from 3.25\u00b11.18 to 2.60\u00b10.96 mg\/dl;\n P<\/jats:italic>\n =0.04) compared with amlodipine (from 430.1\u00b1145.8 to 411.9\u00b1157.6 pg\/ml and from 2.94\u00b10.56 to 2.69\u00b11.52 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 \u22120.68 mg\/dl; 95% confidence interval, \u22120.15 to \u22121.33) with valsartan\/hydrochlorothiazide treatment (\n P<\/jats:italic>\n =0.03 and\n P<\/jats:italic>\n =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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.02700313","type":"journal-article","created":{"date-parts":[[2013,8,9]],"date-time":"2013-08-09T02:15:25Z","timestamp":1376014525000},"page":"1899-1905","source":"Crossref","is-referenced-by-count":75,"title":["Effect of Renin-Angiotensin System Blockade on Soluble Klotho in Patients with Type 2 Diabetes, Systolic Hypertension, and Albuminuria"],"prefix":"10.2215","volume":"8","author":[{"given":"Janaka","family":"Karalliedde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Maltese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Viberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Gnudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-11-20230811","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/MNH.0b013e32835422ad","article-title":"Klotho in health and disease.","volume":"21","author":"Kuro-o","year":"2012","journal-title":"Curr Opin Nephrol 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