{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:56:25Z","timestamp":1790268985870,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>We tested the hypothesis that high plasma FGF23 is an independent risk factor for CKD progression in 419 children, aged 1\u201316 years, enrolled in the Chronic Kidney Disease in Children (CKiD) cohort study. We measured plasma FGF23 concentrations at baseline and determined GFR annually using plasma disappearance of iohexol or the CKiD study estimating equation. We analyzed the association of baseline FGF23 with risk of progression to the composite end point, defined as start of dialysis or kidney transplantation or 50% decline from baseline GFR, adjusted for demographics, baseline GFR, proteinuria, other CKD-specific factors, and other mineral metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At enrollment, median age was 11 years [interquartile range (IQR), 8\u201315], GFR was 44 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      (IQR, 33\u201357), and FGF23 was 132 RU\/ml (IQR, 88\u2013200). During a median follow-up of 5.5 years (IQR, 3.5\u20136.6), 32.5% of children reached the progression end point. Higher FGF23 concentrations were independently associated with higher risk of the composite outcome (fully adjusted hazard ratio, 2.52 in the highest versus lowest FGF23 tertile; 95% confidence interval, 1.44 to 4.39,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.002; fully adjusted hazard ratio, 1.33 per doubling of FGF23; 95% confidence interval, 1.13 to 1.56,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001). The time to progression was 40% shorter for participants in the highest compared with the lowest FGF23 tertile. In contrast, serum phosphorus, vitamin D metabolites, and parathyroid hormone did not consistently associate with progression in adjusted analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High plasma FGF23 is an independent risk factor for CKD progression in children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.02110216","type":"journal-article","created":{"date-parts":[[2016,8,25]],"date-time":"2016-08-25T21:41:33Z","timestamp":1472161293000},"page":"1989-1998","source":"Crossref","is-referenced-by-count":68,"title":["Fibroblast Growth Factor 23 and Risk of CKD Progression in Children"],"prefix":"10.2215","volume":"11","author":[{"given":"Anthony A.","family":"Portale","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myles S.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Messinger","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzana","family":"Perwad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Warady","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Furth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro B.","family":"Salusky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Los Angeles, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,8,25]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1681\/ASN.2005010052","article-title":"Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease.","volume":"16","author":"Gutierrez","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B2-20230813","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":"B3-20230813","doi-asserted-by":"crossref","first-page":"344","DOI":"10.2215\/CJN.05840513","article-title":"Disordered FGF23 and mineral metabolism in children with CKD.","volume":"9","author":"Portale","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1074\/jbc.M207872200","article-title":"Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1\u03b1,25-dihydroxyvitamin D3 production.","volume":"278","author":"Saito","year":"2003","journal-title":"J Biol Chem"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.","volume":"19","author":"Shimada","year":"2004","journal-title":"J Bone Miner Res"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"F1577","DOI":"10.1152\/ajprenal.00463.2006","article-title":"Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro.","volume":"293","author":"Perwad","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"B7-20230813","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/jbmr.1846","article-title":"Sex and age modify biochemical and skeletal manifestations of chronic hyperparathyroidism by altering target organ responses to Ca2+ and parathyroid hormone in mice.","volume":"28","author":"Cheng","year":"2013","journal-title":"J Bone Miner Res"},{"key":"B8-20230813","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.","volume":"359","author":"Guti\u00e9rrez","year":"2008","journal-title":"N Engl J Med"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1001\/jama.2011.826","article-title":"Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease.","volume":"305","author":"Isakova","year":"2011","journal-title":"JAMA"},{"key":"B10-20230813","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1161\/CIRCULATIONAHA.108.844506","article-title":"Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease.","volume":"119","author":"Guti\u00e9rrez","year":"2009","journal-title":"Circulation"},{"key":"B11-20230813","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":"B12-20230813","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1681\/ASN.2013050465","article-title":"Fibroblast growth factor-23 and cardiovascular events in CKD.","volume":"25","author":"Scialla","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1681\/ASN.2006080936","article-title":"Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study.","volume":"18","author":"Fliser","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B14-20230813","doi-asserted-by":"crossref","first-page":"727","DOI":"10.2215\/CJN.10331011","article-title":"FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy.","volume":"7","author":"Lundberg","year":"2012","journal-title":"Clin J Am Soc Nephrol"},{"key":"B15-20230813","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1681\/ASN.2012070713","article-title":"Mineral metabolites and CKD progression in African Americans.","volume":"24","author":"Scialla","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1093\/ndt\/gfr126","article-title":"Mineral abnormalities and long-term graft function in pediatric renal transplant recipients: a role for FGF-23?","volume":"26","author":"Wesseling-Perry","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1681\/ASN.2010080894","article-title":"Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality.","volume":"22","author":"Wolf","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B18-20230813","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1056\/NEJMoa031643","article-title":"Long-term survival of children with end-stage renal disease.","volume":"350","author":"McDonald","year":"2004","journal-title":"N Engl J Med"},{"key":"B19-20230813","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s00467-006-0410-1","article-title":"Chronic kidney disease in children: the global perspective.","volume":"22","author":"Warady","year":"2007","journal-title":"Pediatr Nephrol"},{"key":"B20-20230813","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1001\/jama.2013.4208","article-title":"Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010.","volume":"309","author":"Mitsnefes","year":"2013","journal-title":"JAMA"},{"issue":"Suppl","key":"B21-20230813","doi-asserted-by":"crossref","first-page":"A7","DOI":"10.1053\/j.ajkd.2013.11.001","article-title":"US Renal Data System 2013 Annual Data Report.","volume":"63","author":"Collins","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"B22-20230813","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1053\/j.ajkd.2015.01.008","article-title":"Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and Adolescents: The\u00a0Chronic Kidney Disease in Children (CKiD) Cohort.","volume":"65","author":"Warady","year":"2015","journal-title":"Am J Kidney Dis"},{"key":"B23-20230813","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.2215\/CJN.01941205","article-title":"Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study.","volume":"1","author":"Furth","year":"2006","journal-title":"Clin J Am Soc Nephrol"},{"key":"B24-20230813","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1542\/peds.58.2.259","article-title":"A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine.","volume":"58","author":"Schwartz","year":"1976","journal-title":"Pediatrics"},{"key":"B25-20230813","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1038\/sj.ki.5000385","article-title":"Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children.","volume":"69","author":"Schwartz","year":"2006","journal-title":"Kidney Int"},{"key":"B26-20230813","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/ki.2012.169","article-title":"Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C.","volume":"82","author":"Schwartz","year":"2012","journal-title":"Kidney Int"},{"key":"B27-20230813","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.clinbiochem.2009.07.013","article-title":"An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D.","volume":"42","author":"Wagner","year":"2009","journal-title":"Clin Biochem"},{"key":"B28-20230813","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.clinbiochem.2004.06.006","article-title":"Analytical and clinical validation of the 25 OH vitamin D assay for the LIAISON automated analyzer.","volume":"37","author":"Ersfeld","year":"2004","journal-title":"Clin Biochem"},{"key":"B29-20230813","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1093\/clinchem\/42.4.586","article-title":"Quantification of circulating 1,25-dihydroxyvitamin D by radioimmunoassay with 125I-labeled tracer.","volume":"42","author":"Hollis","year":"1996","journal-title":"Clin Chem"},{"issue":"Suppl 4th Report","key":"B30-20230813","first-page":"555","article-title":"The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents.","volume":"114","year":"2004","journal-title":"Pediatrics"},{"key":"B31-20230813","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1093\/clinchem\/34.8.1625","article-title":"Age- and sex-specific pediatric reference intervals and correlations for zinc, copper, selenium, iron, vitamins A and E, and related proteins.","volume":"34","author":"Lockitch","year":"1988","journal-title":"Clin Chem"},{"key":"B32-20230813","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1681\/ASN.2010121224","article-title":"FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.","volume":"22","author":"Kendrick","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B33-20230813","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2215\/CJN.04250510","article-title":"FGF-23 as a predictor of renal outcome in diabetic nephropathy.","volume":"6","author":"Titan","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B34-20230813","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1681\/ASN.2014020218","article-title":"Serum fibroblast growth factor-23 is associated with incident kidney disease.","volume":"26","author":"Rebholz","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B35-20230813","doi-asserted-by":"crossref","DOI":"10.1681\/ASN.2014090947","article-title":"Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD.","author":"Shroff","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B36-20230813","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2215\/CJN.07480714","article-title":"Progression of pediatric CKD of nonglomerular origin in the CKiD cohort.","volume":"10","author":"Fathallah-Shaykh","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B37-20230813","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1046\/j.1523-1755.1998.00951.x","article-title":"Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats.","volume":"53","author":"Schwarz","year":"1998","journal-title":"Kidney Int"},{"key":"B38-20230813","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/ki.2008.408","article-title":"Suppression of renin-angiotensin gene expression in the kidney by paricalcitol.","volume":"74","author":"Freundlich","year":"2008","journal-title":"Kidney Int"},{"key":"B39-20230813","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1111\/j.1523-1755.2005.00755.x","article-title":"Antiproteinuric effect of oral paricalcitol in chronic kidney disease.","volume":"68","author":"Agarwal","year":"2005","journal-title":"Kidney Int"},{"key":"B40-20230813","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0140-6736(10)61032-X","article-title":"Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial.","volume":"376","author":"de Zeeuw","year":"2010","journal-title":"Lancet"},{"key":"B41-20230813","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.2215\/CJN.07851109","article-title":"Association between clinical risk factors and progression of chronic kidney disease in children.","volume":"5","author":"Staples","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B42-20230813","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1681\/ASN.2005101101","article-title":"Baseline predictors of renal disease progression in the African American Study of Hypertension and Kidney Disease.","volume":"17","author":"Norris","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B43-20230813","doi-asserted-by":"crossref","first-page":"825","DOI":"10.2215\/CJN.02101205","article-title":"Association of disorders in mineral metabolism with progression of chronic kidney disease.","volume":"1","author":"Schwarz","year":"2006","journal-title":"Clin J Am Soc Nephrol"},{"key":"B44-20230813","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/ki.2013.145","article-title":"No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease.","volume":"84","author":"Mehrotra","year":"2013","journal-title":"Kidney Int"},{"key":"B45-20230813","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1093\/ndt\/gfu190","article-title":"Treatment of established left ventricular hypertrophy with fibroblast growth factor receptor blockade in an animal model of CKD.","volume":"29","author":"Di Marco","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"B46-20230813","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.cmet.2015.09.002","article-title":"Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy.","volume":"22","author":"Grabner","year":"2015","journal-title":"Cell Metab"},{"key":"B47-20230813","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.2215\/CJN.07100810","article-title":"Metabolic abnormalities, cardiovascular disease risk factors, and GFR decline in children with chronic kidney disease.","volume":"6","author":"Furth","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B48-20230813","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1053\/j.ajkd.2015.08.020","article-title":"Discordance Between Iothalamate and Iohexol Urinary\u00a0Clearances.","volume":"67","author":"Seegmiller","year":"2016","journal-title":"Am J Kidney Dis"},{"key":"B49-20230813","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1053\/j.ajkd.2014.04.010","article-title":"Measuring GFR: a systematic review.","volume":"64","author":"Soveri","year":"2014","journal-title":"Am J Kidney Dis"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201611000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:46:46Z","timestamp":1786369606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201611000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,25]]},"references-count":49,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.02110216","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,25]]}}}