{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:53:33Z","timestamp":1789786413355,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Fibroblast growth factor 23 (FGF23) levels are elevated in patients with autosomal dominant polycystic kidney disease (ADPKD) and X-linked hypophosphatemia (XLH), but only the latter is characterized by a renal phosphate wasting phenotype. This study explored potential mechanisms underlying resistance to FGF23 in ADPKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      FGF23 and Klotho levels were measured, and renal phosphate transport was evaluated by calculating the ratio of the maximum rate of tubular phosphate reabsorption to GFR (TmP\/GFR) in 99 ADPKD patients, 32 CKD patients, 12 XLH patients, and 20 healthy volunteers. ADPKD and CKD patients were classified by estimated GFR (CKD stage 1, \u226590 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ; CKD stage 2, 60\u201389 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ADPKD patients had 50% higher FGF23 levels than did XLH patients; TmP\/GFR was near normal in most ADPKD patients and very low in XLH patients. Serum Klotho levels were lowest in the ADPKD group, whereas the CKD and XLH groups and volunteers had similar levels. ADPKD patients with an apparent renal phosphate leak had two-fold higher Klotho levels than those without. Serum Klotho values correlated inversely with cyst volume and kidney growth.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Loss of Klotho might be a consequence of cyst growth and constrain the phosphaturic effect of FGF23 in most patients with ADPKD. Normal serum Klotho levels were associated with normal FGF23 biologic activity in all XLH patients and a minority of ADPKD patients. Loss of Klotho and FGF23 increase appear to exceed and precede the changes that can be explained by loss of GFR in patients with ADPKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.09020911","type":"journal-article","created":{"date-parts":[[2011,12,22]],"date-time":"2011-12-22T23:47:06Z","timestamp":1324597626000},"page":"248-257","source":"Crossref","is-referenced-by-count":69,"title":["Soluble Klotho and Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.2215","volume":"7","author":[{"given":"Ivana","family":"Pavik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Jaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Ebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Poster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Krauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas D.","family":"Kistler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Rentsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav","family":"Andreisek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten A.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Devuyst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf P.","family":"W\u00fcthrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas L.","family":"Serra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-9-20230811","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1038\/ki.1994.354","article-title":"Hereditary and acquired cystic disease of the kidney.","volume":"46","author":"Fick","year":"1994","journal-title":"Kidney Int"},{"key":"R2-9-20230811","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/S0140-6736(07)60601-1","article-title":"Autosomal dominant polycystic kidney disease.","volume":"369","author":"Torres","year":"2007","journal-title":"Lancet"},{"key":"R4-9-20230811","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1053\/j.ajkd.2009.03.020","article-title":"Kidney function and volume progression in unilateral autosomal dominant polycystic kidney disease with contralateral renal agenesis or hypoplasia: A case series.","volume":"54","author":"Poster","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"R5-9-20230811","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1053\/j.ajkd.2003.12.026","article-title":"Patients with autosomal dominant polycystic kidney disease hyperfiltrate early in their disease.","volume":"43","author":"Wong","year":"2004","journal-title":"Am J Kidney Dis"},{"key":"R6-9-20230811","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/jmicro\/dfp032","article-title":"FGF23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling.","volume":"58","author":"Ubaidus","year":"2009","journal-title":"J Electron Microsc (Tokyo"},{"key":"R7-9-20230811","doi-asserted-by":"crossref","first-page":"E38","DOI":"10.1152\/ajpendo.00008.2006","article-title":"Pathogenic role of Fgf23 in Hyp mice.","volume":"291","author":"Liu","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"R8-9-20230811","doi-asserted-by":"crossref","first-page":"6500","DOI":"10.1073\/pnas.101545198","article-title":"Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.","volume":"98","author":"Shimada","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"R9-9-20230811","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1056\/NEJMoa020881","article-title":"Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia.","volume":"348","author":"Jonsson","year":"2003","journal-title":"N Engl J Med"},{"key":"R10-9-20230811","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.","volume":"26","author":"White","year":"2000","journal-title":"Nat Genet"},{"key":"R11-9-20230811","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1046\/j.1523-1755.2001.00064.x","article-title":"Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23.","volume":"60","author":"White","year":"2001","journal-title":"Kidney Int"},{"key":"R12-9-20230811","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/ng1868","article-title":"DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.","volume":"38","author":"Lorenz-Depiereux","year":"2006","journal-title":"Nat Genet"},{"key":"R13-9-20230811","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1038\/ng1905","article-title":"Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism.","volume":"38","author":"Feng","year":"2006","journal-title":"Nat Genet"},{"key":"R14-9-20230811","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/ng1095-130","article-title":"A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets.","volume":"11","author":"Francis","year":"1995","journal-title":"Nat Genet"},{"key":"R15-9-20230811","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/ki.2008.643","article-title":"Latest findings in phosphate homeostasis.","volume":"75","author":"Pri\u00e9","year":"2009","journal-title":"Kidney Int"},{"key":"R16-9-20230811","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":"R17-9-20230811","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":"R18-9-20230811","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/ki.2010.375","article-title":"Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate.","volume":"79","author":"Pavik","year":"2011","journal-title":"Kidney Int"},{"key":"R19-9-20230811","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":"R20-9-20230811","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1006\/bbrc.1997.8019","article-title":"Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein.","volume":"242","author":"Matsumura","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"R21-9-20230811","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":"R22-9-20230811","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.bbrc.2010.06.110","article-title":"Establishment of sandwich ELISA for soluble alpha-Klotho measurement: Age-dependent change of soluble alpha-Klotho levels in healthy subjects.","volume":"398","author":"Yamazaki","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"R23-9-20230811","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2369-8-13","article-title":"Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study.","volume":"8","author":"Serra","year":"2007","journal-title":"BMC Nephrol"},{"key":"R24-9-20230811","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa0907419","article-title":"Sirolimus and kidney growth in autosomal dominant polycystic kidney disease.","volume":"363","author":"Serra","year":"2010","journal-title":"N Engl J Med"},{"key":"R25-9-20230811","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1148\/radiology.211.3.r99jn19623","article-title":"Renal volume measurements: Accuracy and repeatability of US compared with that of MR imaging.","volume":"211","author":"Bakker","year":"1999","journal-title":"Radiology"},{"key":"R26-9-20230811","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":"R27-9-20230811","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00862587","article-title":"Assessment of maximal tubular phosphate reabsorption: Comparison of direct measurement with the nomogram of Bijvoet.","volume":"2","author":"Brodehl","year":"1988","journal-title":"Pediatr Nephrol"},{"key":"R28-9-20230811","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1177\/000456329803500203","article-title":"Renal tubular reabsorption of phosphate (TmP\/GFR): Indications and interpretation.","volume":"35","author":"Payne","year":"1998","journal-title":"Ann Clin Biochem"},{"key":"R29-9-20230811","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate.","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"R30-9-20230811","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":"R31-9-20230811","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":"R32-9-20230811","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":"R33-9-20230811","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1046\/j.1523-1755.1999.00370.x","article-title":"New insights into the molecular pathophysiology of polycystic kidney disease.","volume":"55","author":"Murcia","year":"1999","journal-title":"Kidney Int"},{"key":"R34-9-20230811","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1046\/j.1523-1755.2001.00473.x","article-title":"The pck rat: a new model that resembles human autosomal dominant polycystic kidney and liver disease.","volume":"59","author":"Lager","year":"2001","journal-title":"Kidney Int"},{"key":"R35-9-20230811","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":"R36-9-20230811","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 USA"},{"key":"R37-9-20230811","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"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201202000-00009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:41:41Z","timestamp":1786369301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201202000-00009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.09020911","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13988975.15445087","asserted-by":"object"}]},"ISSN":["1555-9041"],"issn-type":[{"value":"1555-9041","type":"print"}],"subject":[],"published":{"date-parts":[[2012,2]]}}}