{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:57:40Z","timestamp":1792799860387,"version":"4.5.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T00:00:00Z","timestamp":1453680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0144121","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T19:19:37Z","timestamp":1453749577000},"page":"e0144121","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating \u03b1-Klotho Concentrations"],"prefix":"10.1371","volume":"11","author":[{"given":"Aaltje Y.","family":"Adema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans J.","family":"van Ittersum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G.","family":"Hoenderop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"de Borst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabath W.","family":"Nanayakkara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piet M.","family":"Ter Wee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke C.","family":"Heijboer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Vervloet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NIGRAM consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,1,25]]},"reference":[{"issue":"12 Suppl","key":"ref1","first-page":"S16","article-title":"Epidemiology of cardiovascular disease in chronic renal disease","volume":"9","author":"RN Foley","year":"1998","journal-title":"Journal of the American Society of Nephrology: JASN"},{"issue":"6","key":"ref2","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.semnephrol.2014.09.005","article-title":"New insights into the FGF23-Klotho axis","volume":"34","author":"H Olauson","year":"2014","journal-title":"Seminars in nephrology"},{"issue":"9784","key":"ref3","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/S0140-6736(11)60739-3","article-title":"The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial","volume":"377","author":"C Baigent","year":"2011","journal-title":"Lancet"},{"issue":"6655","key":"ref4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"M Kuro-o","year":"1997","journal-title":"Nature"},{"issue":"9","key":"ref5","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1096\/fj.10-154765","article-title":"Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule","volume":"24","author":"MC Hu","year":"2010","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1515\/BC.2008.028","article-title":"Klotho as a regulator of oxidative stress and senescence","volume":"389","author":"M Kuro-o","year":"2008","journal-title":"Biological chemistry"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1161\/01.HYP.0000013734.33441.EA","article-title":"In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage","volume":"39","author":"H Mitani","year":"2002","journal-title":"Hypertension"},{"issue":"7","key":"ref8","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/ki.2011.445","article-title":"Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation","volume":"81","author":"CY Sun","year":"2012","journal-title":"Kidney international"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1093\/ndt\/gfq537","article-title":"Angiotensin II blockade upregulates the expression of Klotho, the anti-ageing gene, in an experimental model of chronic cyclosporine nephropathy","volume":"26","author":"HE Yoon","year":"2011","journal-title":"Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association\u2014European Renal Association"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1053\/j.ajkd.2013.01.024","article-title":"Circulating alpha-klotho levels in CKD and relationship to progression. American journal of kidney diseases: the official journal of the","volume":"61","author":"HR Kim","year":"2013","journal-title":"National Kidney Foundation"},{"issue":"9","key":"ref11","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1111\/j.1532-5415.2011.03558.x","article-title":"Plasma klotho and cardiovascular disease in adults","volume":"59","author":"RD Semba","year":"2011","journal-title":"Journal of the American Geriatrics Society"},{"issue":"2","key":"ref12","doi-asserted-by":"crossref","first-page":"e56695","DOI":"10.1371\/journal.pone.0056695","article-title":"A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease","volume":"8","author":"M Kitagawa","year":"2013","journal-title":"PloS one"},{"issue":"1","key":"ref13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1681\/ASN.2009121311","article-title":"Klotho deficiency causes vascular calcification in chronic kidney disease","volume":"22","author":"MC Hu","year":"2011","journal-title":"Journal of the American Society of Nephrology: JASN"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1210\/me.2003-0048","article-title":"Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system","volume":"17","author":"H Tsujikawa","year":"2003","journal-title":"Molecular endocrinology (Baltimore, Md)"},{"issue":"3","key":"ref15","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.bbrc.2011.09.117","article-title":"Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells","volume":"414","author":"RE Forster","year":"2011","journal-title":"Biochemical and biophysical research communications"},{"issue":"1\u20132","key":"ref16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jsbmb.2010.03.019","article-title":"The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging","volume":"121","author":"MR Haussler","year":"2010","journal-title":"The Journal of steroid biochemistry and molecular biology"},{"issue":"6","key":"ref17","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/ki.2008.244","article-title":"Klotho is a target gene of PPAR-gamma","volume":"74","author":"H Zhang","year":"2008","journal-title":"Kidney international"},{"issue":"6","key":"ref18","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/ki.2008.382","article-title":"PPAR-gamma and aging: one link through klotho?","volume":"74","author":"R Zhang","year":"2008","journal-title":"Kidney international"},{"issue":"6","key":"ref19","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1291\/hypres.24.705","article-title":"Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors","volume":"24","author":"T Yamagishi","year":"2001","journal-title":"Hypertension research: official journal of the Japanese Society of Hypertension"},{"issue":"11","key":"ref20","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1681\/ASN.2008111138","article-title":"The PPARgamma agonist pioglitazone ameliorates aging-related progressive renal injury. Journal of the American Society of Nephrology","volume":"20","author":"HC Yang","year":"2009","journal-title":"JASN"},{"issue":"1\u20133","key":"ref21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S0014-5793(03)00894-9","article-title":"Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat","volume":"551","author":"K Saito","year":"2003","journal-title":"FEBS letters"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1159\/000086500","article-title":"Oxidative stress decreases klotho expression in a mouse kidney cell line","volume":"101","author":"M Mitobe","year":"2005","journal-title":"Nephron Experimental nephrology"},{"issue":"2","key":"ref23","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijcard.2007.02.029","article-title":"HMG-CoA reductase inhibition improves anti-aging klotho protein expression and arteriosclerosis in rats with chronic inhibition of nitric oxide synthesis","volume":"123","author":"N Kuwahara","year":"2008","journal-title":"International journal of cardiology"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.cardiores.2004.07.011","article-title":"HMG-CoA reductase inhibitors up-regulate anti-aging klotho mRNA via RhoA inactivation in IMCD3 cells","volume":"64","author":"H Narumiya","year":"2004","journal-title":"Cardiovascular research"},{"issue":"12","key":"ref25","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1001\/archinte.167.12.1262","article-title":"Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study","volume":"167","author":"PW Nanayakkara","year":"2007","journal-title":"Archives of internal medicine"},{"issue":"9","key":"ref26","first-page":"2283","article-title":"Laboratory aspects of circulating alpha-Klotho. Nephrology, dialysis, transplantation: official publication of the","volume":"28","author":"AC Heijboer","year":"2013","journal-title":"European Dialysis and Transplant Association\u2014European Renal Association"},{"issue":"Pt 4","key":"ref27","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1258\/acb.2009.009066","article-title":"Determination of fibroblast growth factor 23","volume":"46","author":"AC Heijboer","year":"2009","journal-title":"Annals of clinical biochemistry"},{"key":"ref28","first-page":"1","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","year":"2013","journal-title":"Kidney Int Suppl"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1006\/bbrc.1998.9246","article-title":"Downregulation of the Klotho gene in the kidney under sustained circulatory stress in rats","volume":"249","author":"H Aizawa","year":"1998","journal-title":"Biochemical and biophysical research communications"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1096\/fj.02-0448fje","article-title":"Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress","volume":"17","author":"T Nagai","year":"2003","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"4","key":"ref31","doi-asserted-by":"crossref","first-page":"e123","DOI":"10.1159\/000342117","article-title":"Statin Upregulates the Expression of Klotho, an Anti-Aging Gene, in Experimental Cyclosporine Nephropathy","volume":"120","author":"HE Yoon","year":"2012","journal-title":"Nephron Experimental nephrology"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1253\/circj.67.816","article-title":"Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in hypercholesterolemic patients","volume":"67","author":"A Tamura","year":"2003","journal-title":"Circulation journal: official journal of the Japanese Circulation Society"},{"issue":"2","key":"ref33","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3988\/jcn.2014.10.2.140","article-title":"Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease","volume":"10","author":"GJ Moon","year":"2014","journal-title":"Journal of clinical neurology (Seoul, Korea)"},{"issue":"1\u20132","key":"ref34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.cccn.2003.07.020","article-title":"The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients","volume":"338","author":"B Giray","year":"2003","journal-title":"Clinica chimica acta; international journal of clinical chemistry"},{"issue":"11","key":"ref35","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2215\/CJN.02700313","article-title":"Effect of renin-angiotensin system blockade on soluble Klotho in patients with type 2 diabetes, systolic hypertension, and albuminuria","volume":"8","author":"J Karalliedde","year":"2013","journal-title":"Clinical journal of the American Society of Nephrology: CJASN"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.clinbiochem.2013.05.046","article-title":"Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays","volume":"46","author":"L Pedersen","year":"2013","journal-title":"Clinical biochemistry"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0144121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:27:05Z","timestamp":1567556825000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0144121"}},"subtitle":[],"editor":[{"given":"Rosa Maria Affonso","family":"Moys\u00e9s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,1,25]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,1,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0144121","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,25]]}}}