{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:15:58Z","timestamp":1791483358619,"version":"4.3.4"},"reference-count":89,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Seminars in Nephrology"],"published-print":{"date-parts":[[2013,3]]},"DOI":"10.1016\/j.semnephrol.2012.12.013","type":"journal-article","created":{"date-parts":[[2013,3,6]],"date-time":"2013-03-06T15:39:13Z","timestamp":1362584353000},"page":"118-129","source":"Crossref","is-referenced-by-count":149,"title":["Renal and Extrarenal Actions of Klotho"],"prefix":"10.1016","volume":"33","author":[{"given":"Ming Chang","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuro-o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orson W.","family":"Moe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.semnephrol.2012.12.013_bib1","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":"Kuro-o","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib2","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone Klotho","volume":"309","author":"Kurosu","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1006\/bbrc.1999.2009","article-title":"Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys","volume":"267","author":"Kato","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib4","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":"Hu","year":"2010","journal-title":"FASEB J"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib5","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":"Forster","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib6","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":"Mitobe","year":"2005","journal-title":"Nephron Exp Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib7","doi-asserted-by":"crossref","first-page":"19796","DOI":"10.1073\/pnas.0709805104","article-title":"Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17","volume":"104","author":"Chen","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.febslet.2004.03.090","article-title":"Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane","volume":"565","author":"Imura","year":"2004","journal-title":"FEBS Lett"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib9","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":"Hu","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib10","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1073\/pnas.0902006107","article-title":"Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formation","volume":"107","author":"Goetz","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib11","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nature05315","article-title":"Klotho converts canonical FGF receptor into a specific receptor for FGF23","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib12","doi-asserted-by":"crossref","first-page":"6120","DOI":"10.1074\/jbc.C500457200","article-title":"Regulation of fibroblast growth factor-23 signaling by klotho","volume":"281","author":"Kurosu","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib13","doi-asserted-by":"crossref","first-page":"1483.e25","DOI":"10.1016\/j.neurobiolaging.2011.12.018","article-title":"Nuclear localization of Klotho in brain: an anti-aging protein","volume":"33","author":"German","year":"2012","journal-title":"Neurobiol Aging"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib14","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/ncb2167","article-title":"Klotho suppresses RIG-I-mediated senescence-associated inflammation","volume":"13","author":"Liu","year":"2011","journal-title":"Nat Cell Biol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib15","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1210\/en.143.2.683","article-title":"Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene","volume":"143","author":"Yoshida","year":"2002","journal-title":"Endocrinology"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib16","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":"Tsujikawa","year":"2003","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib17","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/ki.2009.24","article-title":"Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase","volume":"75","author":"Ohnishi","year":"2009","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib18","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1096\/fj.09-152488","article-title":"Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging","volume":"24","author":"Ohnishi","year":"2010","journal-title":"FASEB J"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib19","doi-asserted-by":"crossref","first-page":"F769","DOI":"10.1152\/ajprenal.00248.2006","article-title":"Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice","volume":"292","author":"Segawa","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib20","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1159\/000331737","article-title":"Downregulation of NaPi-IIa and NaPi-IIb Na-coupled phosphate transporters by coexpression of Klotho","volume":"28","author":"Dermaku-Sopjani","year":"2011","journal-title":"Cell Physiol Biochem"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib21","doi-asserted-by":"crossref","first-page":"9805","DOI":"10.1073\/pnas.0803223105","article-title":"Removal of sialic acid involving Klotho causes cell-surface retention of TRPV5 channel via binding to galectin-1","volume":"105","author":"Cha","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1126\/science.1114245","article-title":"The beta-glucuronidase klotho hydrolyzes and activates the TRPV5 channel","volume":"310","author":"Chang","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib23","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1124\/mol.109.055780","article-title":"Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho","volume":"76","author":"Cha","year":"2009","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib24","doi-asserted-by":"crossref","first-page":"9777","DOI":"10.1074\/jbc.M312392200","article-title":"Klotho is a novel beta-glucuronidase capable of hydrolyzing steroid beta-glucuronides","volume":"279","author":"Tohyama","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib25","doi-asserted-by":"crossref","first-page":"F689","DOI":"10.1152\/ajprenal.00007.2009","article-title":"PiT-2 coming out of the pits","volume":"296","author":"Moe","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib26","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1093\/jn\/131.12.3182","article-title":"The progression of aging in klotho mutant mice can be modified by dietary phosphorus and zinc","volume":"131","author":"Morishita","year":"2001","journal-title":"J Nutr"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1582-4934.2004.tb00274.x","article-title":"Inorganic phosphate homeostasis and the role of dietary phosphorus","volume":"8","author":"Takeda","year":"2004","journal-title":"J Cell Mol Med"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib28","first-page":"4003","article-title":"The parathyroid is a target organ for FGF23 in rats","volume":"117","author":"Ben-Dov","year":"2007","journal-title":"J Clin Invest"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib29","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1161\/01.CIR.0000124224.48962.32","article-title":"Sinoatrial node dysfunction and early unexpected death of mice with a defect of klotho gene expression","volume":"109","author":"Takeshita","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib30","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1681\/ASN.2009040427","article-title":"FGF23 fails to inhibit uremic parathyroid glands","volume":"21","author":"Canalejo","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib31","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1210\/en.139.4.1692","article-title":"Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands","volume":"139","author":"Tatsumi","year":"1998","journal-title":"Endocrinology"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib32","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1126\/science.1135901","article-title":"alpha-Klotho as a regulator of calcium homeostasis","volume":"316","author":"Imura","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib33","doi-asserted-by":"crossref","first-page":"F1466","DOI":"10.1152\/ajprenal.00279.2009","article-title":"Regulation of rat intestinal Na-dependent phosphate transporters by dietary phosphate","volume":"297","author":"Giral","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib34","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1126\/science.1143578","article-title":"Augmented Wnt signaling in a mammalian model of accelerated aging","volume":"317","author":"Liu","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib35","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1447-0594.2011.00699.x","article-title":"Klotho protein diminishes endothelial apoptosis and senescence via a mitogen-activated kinase pathway","volume":"11","author":"Maekawa","year":"2011","journal-title":"Geriatr Gerontol Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib36","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.1016\/j.febslet.2006.09.036","article-title":"Klotho RNAi induces premature senescence of human cells via a p53\/p21 dependent pathway","volume":"580","author":"de Oliveira","year":"2006","journal-title":"FEBS Lett"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib37","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.4161\/cc.6.24.5084","article-title":"High NaCl promotes cellular senescence","volume":"6","author":"Dmitrieva","year":"2007","journal-title":"Cell Cycle"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib38","doi-asserted-by":"crossref","first-page":"H1673","DOI":"10.1152\/ajpheart.00455.2009","article-title":"Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition","volume":"297","author":"Nakano-Kurimoto","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib39","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1073\/pnas.0611079104","article-title":"Amelioration of progressive renal injury by genetic manipulation of Klotho gene","volume":"104","author":"Haruna","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib40","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/ndt\/gfp451","article-title":"Klotho reduces apoptosis in experimental ischaemic acute kidney injury via HSP-70","volume":"25","author":"Sugiura","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib41","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1006\/bbrc.1998.8943","article-title":"Klotho protein protects against endothelial dysfunction","volume":"248","author":"Saito","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib42","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1007\/s000180050038","article-title":"Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases","volume":"57","author":"Nagai","year":"2000","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib43","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1161\/01.CIR.0000139854.74847.99","article-title":"Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse","volume":"110","author":"Shimada","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib44","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/S0006-291X(02)00216-4","article-title":"Regulation of angiogenesis by the aging suppressor gene klotho","volume":"293","author":"Fukino","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib45","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1172\/JCI200319270","article-title":"Targeted disruption of TGF-beta1\/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction","volume":"112","author":"Sato","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib46","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1055\/s-2002-36699","article-title":"Increased expression of plasminogen activator inhibitor-1 with fibrin deposition in a murine model of aging, \u201cKlotho\u201d mouse","volume":"28","author":"Takeshita","year":"2002","journal-title":"Semin Thromb Hemost"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib47","doi-asserted-by":"crossref","first-page":"F1252","DOI":"10.1152\/ajprenal.00294.2011","article-title":"Reduced klotho expression level in kidney aggravates renal interstitial fibrosis","volume":"302","author":"Sugiura","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib48","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1074\/jbc.M110.174037","article-title":"Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice","volume":"286","author":"Doi","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib49","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/nrendo.2012.47","article-title":"Cardiovascular risk in double diabetes mellitus-when two worlds collide","volume":"8","author":"Cleland","year":"2012","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib50","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1253\/circj.CJ-11-1519","article-title":"Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan","volume":"76","author":"Saito","year":"2012","journal-title":"Circ J"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib51","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1681\/ASN.2005010106","article-title":"Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults","volume":"16","author":"Kurella","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib52","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.cca.2011.02.034","article-title":"Association of exonic variants of Klotho with metabolic syndrome in Asian Indians","volume":"412","author":"Majumdar","year":"2011","journal-title":"Clin Chim Acta"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib53","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/ki.2011.423","article-title":"Decreased renal alpha-Klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion","volume":"81","author":"Asai","year":"2012","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib54","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.2337\/db10-1262","article-title":"Klotho depletion contributes to increased inflammation in kidney of the db\/db mouse model of diabetes via RelA (serine)536 phosphorylation","volume":"60","author":"Zhao","year":"2011","journal-title":"Diabetes"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib55","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":"Aizawa","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib56","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":"Yamagishi","year":"2001","journal-title":"Hypertens Res"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib57","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/HYPERTENSIONAHA.109.134320","article-title":"Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage","volume":"54","author":"Wang","year":"2009","journal-title":"Hypertension"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib58","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1006\/bbrc.2000.3470","article-title":"In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome","volume":"276","author":"Saito","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib59","doi-asserted-by":"crossref","first-page":"513853","DOI":"10.1155\/2010\/513853","article-title":"Decrease of Klotho in the kidney of streptozotocin-induced diabetic rats","volume":"2010","author":"Cheng","year":"2010","journal-title":"J Biomed Biotechnol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib60","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nm0106-56","article-title":"Klotho-induced insulin resistance: a blessing in disguise?","volume":"12","author":"Unger","year":"2006","journal-title":"Nat Med"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib61","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1124\/jpet.110.167635","article-title":"Pharmacogenomic, physiological, and biochemical investigations on safety and efficacy biomarkers associated with the peroxisome proliferator-activated receptor-gamma activator rosiglitazone in rodents: a translational medicine investigation","volume":"334","author":"Wang","year":"2010","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib62","doi-asserted-by":"crossref","first-page":"c54","DOI":"10.1159\/000228076","article-title":"Association of secondary hyperparathyroidism with CKD progression, health care costs and survival in diabetic predialysis CKD patients","volume":"113","author":"Schumock","year":"2009","journal-title":"Nephron Clin Pract"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib63","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib64","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/ki.2010.313","article-title":"Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease","volume":"78","author":"Hasegawa","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib65","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s10157-012-0621-7","article-title":"Serum levels of soluble secreted alpha-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis","volume":"16","author":"Shimamura","year":"2012","journal-title":"Clin Exp Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib66","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1210\/jc.2009-1603","article-title":"Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active","volume":"95","author":"Shimada","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib67","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000274483","article-title":"Involvement of alpha-klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism","volume":"31","author":"Kumata","year":"2010","journal-title":"Am J Nephrol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib68","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ki.2009.414","article-title":"Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients","volume":"77","author":"Komaba","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib69","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/ki.2010.260","article-title":"Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients","volume":"78","author":"Krajisnik","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib70","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/ki.2009.464","article-title":"Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease","volume":"77","author":"Galitzer","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib71","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/ki.2010.215","article-title":"Increased parathyroid expression of klotho in uremic rats","volume":"78","author":"Hofman-Bang","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib72","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1172\/JCI31330","article-title":"A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis","volume":"117","author":"Ichikawa","year":"2007","journal-title":"J Clin Invest"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib73","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1096\/fj.08-114397","article-title":"In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis","volume":"23","author":"Nakatani","year":"2009","journal-title":"FASEB J"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib74","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1093\/ndt\/gfr188","article-title":"Lack of association of Klotho gene variants with valvular and vascular calcification in Caucasians: a candidate gene study of the Framingham Offspring Cohort","volume":"26","author":"Tangri","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib75","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.bbrc.2005.11.094","article-title":"Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells","volume":"339","author":"Ikushima","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib76","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijcard.2011.08.850","article-title":"Expression of FGF23\/KLOTHO system in human vascular tissue","author":"Donate-Correa","year":"2011","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib77","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1161\/CIRCULATIONAHA.111.053405","article-title":"Vascular klotho deficiency potentiates the development of human artery calcification and mediates resistance to FGF23","volume":"125","author":"Lim","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib78","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.bbrc.2003.08.131","article-title":"Regulation of stanniocalcin 1 and 2 expression in the kidney by klotho gene","volume":"310","author":"Yahata","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib79","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.bone.2012.01.006","article-title":"Stanniocalcin 2 is associated with ectopic calcification in alpha-klotho mutant mice and inhibits hyperphosphatemia-induced calcification in aortic vascular smooth muscle cells","volume":"50","author":"Takei","year":"2012","journal-title":"Bone"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib80","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1111\/j.1523-1755.2005.09506.x","article-title":"The role of vitamin D in left ventricular hypertrophy and cardiac function","volume":"95","author":"Achinger","year":"2005","journal-title":"Kidney Int Suppl"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib81","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib82","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.atherosclerosis.2009.05.013","article-title":"Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population","volume":"207","author":"Mirza","year":"2009","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib83","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/ndt\/gfi165","article-title":"Klotho reduces apoptosis in experimental ischaemic acute renal failure","volume":"20","author":"Sugiura","year":"2005","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib84","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":"Mitani","year":"2002","journal-title":"Hypertension"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib85","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ki.2010.328","article-title":"Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective","volume":"78","author":"Hu","year":"2010","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib86","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":"Zhang","year":"2008","journal-title":"Kidney Int"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib87","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":"Narumiya","year":"2004","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib88","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":"Yoon","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.semnephrol.2012.12.013_bib89","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s10157-011-0511-4","article-title":"Circulating levels of soluble alpha-Klotho in patients with chronic kidney disease","volume":"15","author":"Sugiura","year":"2011","journal-title":"Clin Exp Nephrol"}],"container-title":["Seminars in Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0270929512002756?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0270929512002756?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T14:53:40Z","timestamp":1562770420000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0270929512002756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":89,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["S0270929512002756"],"URL":"https:\/\/doi.org\/10.1016\/j.semnephrol.2012.12.013","relation":{},"ISSN":["0270-9295"],"issn-type":[{"value":"0270-9295","type":"print"}],"subject":[],"published":{"date-parts":[[2013,3]]}}}