{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:50:49Z","timestamp":1782125449018,"version":"3.54.5"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Currently, uniform reference values for parameters of phosphate (Pi) homeostasis\u2014the phosphaturic hormone fibroblast growth factor 23 (FGF23) and its coreceptor, soluble Klotho (sKlotho)\u2014are used for women and men regardless of age. This may not be adequate, especially in older subjects. We established Lambda\u2013Mu\u2013Sigma (LMS)-based continuous age- and sex-specific reference values for key parameters of Pi homeostasis, FGF23 and sKlotho.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The HAnnover Reference values for Adults study included 504 participants (51% women) aged 18\u201370 years. Main outcome measures were serum Pi, intact (iFGF23) and total FGF23, sKlotho, tubular maximum phosphate reabsorption per glomerular filtration rate (TmP\/GFR), fractional tubular reabsorption of phosphate (TRP), and urinary calcium-to-creatinine (Ca\/Crea) and phosphate-to-creatinine ratios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All parameters examined showed statistically significant differences between the sexes. There was a constant decrease in renal Pi reabsorption capacity (TmP\/GFR, TRP) and serum Pi concentrations in older men, beginning around their sixth decade of life, whereas the parameters of Pi homeostasis in women hardly changed with age. Women had significantly lower iFGF23 but slightly higher total FGF23 concentrations. sKlotho concentrations decreased with age in both sexes, with women generally having higher concentrations than men regardless of the age-related decline in kidney function. Women taking estrogen-containing oral contraceptives had lower sKlotho concentrations than their peers. Women showed higher urine Ca\/Crea values than men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The presented LMS-based continuous reference values for key parameters of Pi homeostasis enable the calculation of standardized z-scores to facilitate test result interpretation in women and men.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ckj\/sfag147","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:49:23Z","timestamp":1778240963000},"source":"Crossref","is-referenced-by-count":0,"title":["Age- and sex-specific reference values for phosphate homeostasis parameters\u2014fibroblast growth factor 23 and soluble Klotho"],"prefix":"10.1093","volume":"19","author":[{"given":"Katharina","family":"Schermuly","sequence":"first","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tschirner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rebe","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9601-7813","authenticated-orcid":false,"given":"Dieter","family":"Haffner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9203-7622","authenticated-orcid":false,"given":"Maren","family":"Leifheit-Nestler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical School , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"2026062206121007000_bib1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1093\/ndt\/gfad188","article-title":"The basics of phosphate metabolism","volume":"39","author":"Wagner","year":"2024","journal-title":"Nephrol Dial Transplant"},{"key":"2026062206121007000_bib2","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/s41581-024-00926-x","article-title":"Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia","volume":"21","author":"Haffner","year":"2025","journal-title":"Nat Rev Nephrol"},{"key":"2026062206121007000_bib3","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1002\/jbmr.4702","article-title":"Determination of FGF23 levels for the diagnosis of FGF23-mediated hypophosphatemia","volume":"37","author":"Hartley","year":"2022","journal-title":"J Bone Miner Res"},{"key":"2026062206121007000_bib4","doi-asserted-by":"publisher","first-page":"4647","DOI":"10.1038\/s41598-024-52701-4","article-title":"The optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease: results from NHANES","volume":"14","author":"Liu","year":"2024","journal-title":"Sci Rep"},{"key":"2026062206121007000_bib5","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.3390\/ijms25031843","article-title":"Soluble Klotho, a potential biomarker of chronic kidney disease\u2013mineral bone disorders involved in healthy ageing: lights and shadows","volume":"25","author":"Mart\u00edn-V\u00edrgala","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2026062206121007000_bib6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1053\/j.ajkd.2008.07.036","article-title":"Serum phosphorus concentrations in the Third National Health and Nutrition Examination Survey (NHANES III)","volume":"53","author":"De\u00a0Boer","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"2026062206121007000_bib7","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1530\/EC-20-0509","article-title":"Age-dependent sex differences in calcium and phosphate homeostasis","volume":"10","author":"Koek","year":"2021","journal-title":"Endocr Connect"},{"key":"2026062206121007000_bib8","doi-asserted-by":"publisher","first-page":"e1885","DOI":"10.1210\/clinem\/dgae633","article-title":"Serum phosphate in the general population: a need for sex-specific reference intervals","volume":"110","author":"Bosman","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062206121007000_bib9","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1093\/ejendo\/lvaf093","article-title":"Soluble alpha klotho\u2014impact of biological variables and reference intervals for adults","volume":"192","author":"Schweizer","year":"2025","journal-title":"Eur J Endocrinol"},{"key":"2026062206121007000_bib10","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1053\/j.ajkd.2013.07.012","article-title":"Effects of sex and postmenopausal estrogen use on serum phosphorus levels: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2003\u20132006","volume":"63","author":"Zhang","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"2026062206121007000_bib11","doi-asserted-by":"publisher","first-page":"100040","DOI":"10.1016\/j.simpa.2020.100040","article-title":"RefCurv: a software for the construction of pediatric reference curves","volume":"6","author":"Winkler","year":"2020","journal-title":"Software Impacts"},{"key":"2026062206121007000_bib12","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1515\/cclm-2022-1077","article-title":"LMS-based continuous reference percentiles for 14 laboratory parameters in the CALIPER cohort of healthy children and adolescents","volume":"61","author":"Wilson","year":"2023","journal-title":"Clin Chem Lab Med"},{"key":"2026062206121007000_bib13","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2024","journal-title":"Kidney Int"},{"key":"2026062206121007000_bib14","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.kint.2025.02.025","article-title":"Age- and sex-specific reference values of estimated glomerular filtration rate for European adults","volume":"107","author":"Astley","year":"2025","journal-title":"Kidney Int"},{"key":"2026062206121007000_bib15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.7326\/M20-4366","article-title":"Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate: a cross-sectional analysis of pooled data","volume":"174","author":"Pottel","year":"2021","journal-title":"Ann Intern Med"},{"key":"2026062206121007000_bib16","doi-asserted-by":"publisher","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":"2026062206121007000_bib17","first-page":"125","article-title":"Direct measurement of TP\/GFR: a simple and reliable parameter of renal phosphate handling","volume":"44","author":"Stark","year":"1986","journal-title":"Nephron"},{"key":"2026062206121007000_bib18","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1097\/01.mnh.0000447020.74593.6f","article-title":"Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease","volume":"23","author":"Wolf","year":"2014","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2026062206121007000_bib19","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1002\/sim.4780111005","article-title":"Smoothing reference centile curves: the LMS method and penalized likelihood","volume":"11","author":"Cole","year":"1992","journal-title":"Stat Med"},{"key":"2026062206121007000_bib20","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1210\/jcem-20-3-364","article-title":"The normal range of serum inorganic phosphorus and its utility as a discriminant in the diagnosis of congenital hypophosphatemia","volume":"20","author":"Greenberg","year":"1960","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062206121007000_bib21","volume-title":"Clinical Methods: The History, Physical, and Laboratory Examinations","author":"Walker","year":"1990","edition":"3rd ed."},{"key":"2026062206121007000_bib22","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1309\/LMGLMZ8CIYMFNOGX","article-title":"Calcium, magnesium, and phosphate","volume":"45","author":"Bazydlo","year":"2014","journal-title":"Lab Med"},{"key":"2026062206121007000_bib23","article-title":"Kapitel 6.3-1 Referenzbereiche f\u00fcr Phosphat","volume-title":"Labor und Diagnose","author":"Thomas","year":"2020","edition":"9th ed."},{"key":"2026062206121007000_bib24","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1056\/NEJMc0800696","article-title":"Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults","volume":"359","author":"Cirillo","year":"2008","journal-title":"N Engl J Med"},{"key":"2026062206121007000_bib25","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1007\/s00467-021-05097-6","article-title":"Renal effects of growth hormone in health and in kidney disease","volume":"36","author":"Haffner","year":"2021","journal-title":"Pediatr Nephrol"},{"key":"2026062206121007000_bib26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1210\/edrv-14-1-20","article-title":"Human growth hormone and human aging","volume":"14","author":"Corpas","year":"1993","journal-title":"Endocr Rev"},{"key":"2026062206121007000_bib27","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.arr.2007.12.005","article-title":"Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men and somatotropic axes in men and women","volume":"7","author":"Veldhuis","year":"2008","journal-title":"Ageing Res Rev"},{"key":"2026062206121007000_bib28","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1093\/gerona\/glab337","article-title":"Do epigenetic clocks provide explanations for sex differences in life span? a cross-sectional twin study","volume":"77","author":"Kankaanp\u00e4\u00e4","year":"2022","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2026062206121007000_bib29","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1093\/ndt\/gfab331","article-title":"Tubular phosphate handling: references from child to adulthood in the era of standardized serum creatinine","volume":"37","author":"Derain","year":"2022","journal-title":"Nephrol Dial Transplant"},{"key":"2026062206121007000_bib30","doi-asserted-by":"publisher","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":"2026062206121007000_bib31","article-title":"Kapitel 6.3.2.2 Fraktionelle tubul\u00e4re Phosphatr\u00fcckresorption, TRP (%)","volume-title":"Labor und Diagnose","author":"Thomas","year":"2020","edition":"9th ed."},{"key":"2026062206121007000_bib32","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11255-015-1149-z","article-title":"Relationship between timed and spot urine collections for measuring phosphate excretion","volume":"48","author":"Tan","year":"2016","journal-title":"Int Urol Nephrol"},{"key":"2026062206121007000_bib33","doi-asserted-by":"publisher","first-page":"sfaf097","DOI":"10.1093\/ckj\/sfaf097","article-title":"Estimating 24-hour urine phosphate excretion from spot urine","volume":"18","author":"Li","year":"2025","journal-title":"Clin Kidney J"},{"key":"2026062206121007000_bib34","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s00198-020-05615-6","article-title":"Reference range for 24-h urine calcium, calcium\/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women","volume":"32","author":"Smith","year":"2021","journal-title":"Osteoporos Int"},{"key":"2026062206121007000_bib35","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1042\/cs0380601","article-title":"Urinary excretion of calcium and creatinine in relation to age and body weight in normal subjects and patients with renal calculus","volume":"38","author":"Bulusu","year":"1970","journal-title":"Clin Sci"},{"key":"2026062206121007000_bib36","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/jbmr.5650050407","article-title":"Effect of age on variables relating to calcium and phosphorus metabolism in women","volume":"5","author":"Kotowicz","year":"1990","journal-title":"J Bone Miner Res"},{"key":"2026062206121007000_bib37","doi-asserted-by":"publisher","first-page":"3357","DOI":"10.1210\/jc.2012-1811","article-title":"Biological variability of plasma intact and C-terminal FGF23 measurements","volume":"97","author":"Smith","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062206121007000_bib38","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1007\/s00223-017-0307-y","article-title":"Evaluation of a new fully automated assay for plasma intact FGF23","volume":"101","author":"Souberbielle","year":"2017","journal-title":"Calcif Tissue Int"},{"key":"2026062206121007000_bib39","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s00774-021-01258-7","article-title":"Performance evaluation of the new chemiluminescent intact FGF23 assay relative to the existing assay system","volume":"40","author":"Kato","year":"2022","journal-title":"J Bone Miner Metab"},{"key":"2026062206121007000_bib40","doi-asserted-by":"publisher","first-page":"e218","DOI":"10.1210\/clinem\/dgae502","article-title":"Cystinosis-associated metabolic bone disease across ages and CKD stages 1 to 5D\/T","volume":"110","author":"Lahring","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062206121007000_bib41","doi-asserted-by":"publisher","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":"Pedersen","year":"2013","journal-title":"Clin Biochem"},{"key":"2026062206121007000_bib42","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.3390\/jcm11092415","article-title":"References values of soluble \u03b1-Klotho serum levels using an enzyme-linked immunosorbent assay in healthy adults aged 18\u201385 years","volume":"11","author":"Espuch-Oliver","year":"2022","journal-title":"J Clin Med"},{"key":"2026062206121007000_bib43","doi-asserted-by":"publisher","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":"2026062206121007000_bib44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/872193","article-title":"Soluble \u03b1 -Klotho serum levels in chronic kidney disease","volume":"2015","author":"Rotondi","year":"2015","journal-title":"Int J Endocrinol"},{"key":"2026062206121007000_bib45","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.clinbiochem.2019.08.010","article-title":"Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: comparisons to traditionally partitioned reference intervals","volume":"73","author":"Asgari","year":"2019","journal-title":"Clin Biochem"},{"key":"2026062206121007000_bib46","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1210\/clinem\/dgad597","article-title":"LMS-based pediatric reference values for parameters of phosphate homeostasis in the HARP Cohort","volume":"109","author":"Pott","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"2026062206121007000_bib47","doi-asserted-by":"publisher","first-page":"383","DOI":"10.2215\/CJN.04730510","article-title":"Effects of dietary phosphate and calcium intake on fibroblast growth factor-23","volume":"6","author":"Vervloet","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026062206121007000_bib48","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1053\/j.jrn.2020.02.004","article-title":"Fibroblast growth factor-23 and vegetarian diet in India","volume":"30","author":"Anand","year":"2020","journal-title":"J Ren Nutr"},{"key":"2026062206121007000_bib49","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1007\/s00198-017-4162-5","article-title":"24-hour profile of serum sclerostin and its association with bone biomarkers in men","volume":"28","author":"Swanson","year":"2017","journal-title":"Osteoporos Int"},{"key":"2026062206121007000_bib50","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.kint.2021.07.013","article-title":"Iron status, fibroblast growth factor 23 and cardiovascular and kidney outcomes in chronic kidney disease","volume":"100","author":"Mehta","year":"2021","journal-title":"Kidney Int"},{"key":"2026062206121007000_bib51","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1097\/MNH.0000000000000614","article-title":"Simultaneous management of disorderd phosphate and iron homeostasis to correct fibroblast growth factor 23 and associated outcomes in chronic kidney disease","volume":"29","author":"Courbon","year":"2020","journal-title":"Curr Opin Nephrol Hypertens"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfag147\/68251445\/sfag147.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/6\/sfag147\/68251445\/sfag147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ckj\/article-pdf\/19\/6\/sfag147\/68251445\/sfag147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:12:30Z","timestamp":1782123150000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/doi\/10.1093\/ckj\/sfag147\/8673153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfag147","relation":{},"ISSN":["2048-8505","2048-8513"],"issn-type":[{"value":"2048-8505","type":"print"},{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,5,8]]},"article-number":"sfag147"}}