{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:05:21Z","timestamp":1784657121372,"version":"3.55.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"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"],"abstract":"\n Background<\/jats:title>\n Albumin-adjusted calcium is widely used despite uncertainty about its accuracy in critically ill adults. We prospectively evaluated the diagnostic performance of total calcium and of multiple published albumin-correction formulae against ionised calcium, the physiological reference standard, in an intensive care unit (ICU) cohort.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective observational cohort study, ionised calcium (iCa), total calcium, albumin, venous pH, creatinine, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), procalcitonin, magnesium, phosphate and vitamin D were measured simultaneously. The primary outcome was the diagnostic accuracy (area under the ROC curve [AUC]; sensitivity\/specificity) of total calcium and of corrected calcium for detecting hypocalcaemia, defined a priori by the reference standard as iCa\u2009<\u20091.12 mmol\/L; the pre-specified contrast was the difference between the two correlated AUCs. Twelve published measures were compared (total calcium; Payne; simplified Payne; Orrell; Berry; James; Jain; Thode; and the Pekar and Antonio estimators). Agreement, formal subgroup interaction tests, an explanatory multivariable model with collinearity diagnostics, and an exploratory internally-validated ICU equation were assessed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In total, 250 patients were enrolled (median age 70 years; 147 men, 58.8%). Hypocalcaemia prevalence was 58.0% (n\u2009=\u2009145). Payne-corrected calcium correctly identified only 15.2% of truly hypocalcaemic patients (Cohen \u03ba\u2009=\u20090.08), versus 62.8% for total calcium (\u03ba\u2009=\u20090.40). No simple albumin-correction formula significantly outperformed unadjusted total calcium (AUC 0.69\u20130.75; all DeLong p\u2009>\u20090.05 vs total calcium AUC 0.74). Only the four-variable Pekar estimator achieved a higher AUC (0.78; p\u2009=\u20090.005). In the explanatory model, only total calcium, pH, and sex independently predicted iCa (all variance inflation factors\u2009<\u20091.8); albumin, phosphate and vitamin D were not significant. An exploratory ICU-specific equation reached an optimism-corrected R\u00b2 of only 0.17.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Albumin-corrected calcium, including all established formulae tested, provides no diagnostic benefit over total calcium in the ICU and frequently masks true hypocalcaemia. Direct ionised-calcium measurement should be prioritised when accurate calcium status affects management. These are diagnostic-accuracy findings; their clinical-outcome implications require outcome-anchored study.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0354233","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:27:31Z","timestamp":1784654851000},"page":"e0354233","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limited diagnostic utility of albumin-corrected calcium in the intensive care unit: A prospective comparison with ionised calcium"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-952X","authenticated-orcid":true,"given":"Erdo\u011fan","family":"\u00d6zdemir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Turgay","family":"Y\u0131lmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deccane","family":"D\u00fczenci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"3","key":"pone.0354233.ref001","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/ndt\/gfae204","article-title":"Biology of calcium homeostasis regulation in intestine and kidney","volume":"40","author":"AL Deluque","year":"2025","journal-title":"Nephrol Dial Transplant"},{"issue":"2","key":"pone.0354233.ref002","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1053\/j.ajkd.2023.04.017","article-title":"Calcium and phosphate disorders: core curriculum 2024","volume":"83","author":"SL Murray","year":"2024","journal-title":"Am J Kidney Dis"},{"issue":"9","key":"pone.0354233.ref003","article-title":"Predictive accuracy of serum total calcium for both critically high and critically low ionized calcium in critical illness","volume":"32","author":"Z-D Hu","year":"2018","journal-title":"J Clin Lab Anal"},{"issue":"5893","key":"pone.0354233.ref004","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1136\/bmj.4.5893.643","article-title":"Interpretation of serum calcium in patients with abnormal serum proteins","volume":"4","author":"RB Payne","year":"1973","journal-title":"Br Med J"},{"issue":"5","key":"pone.0354233.ref005","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1373\/clinchem.2018.300392","article-title":"Albumin-adjusted calcium and ionized calcium for assessing calcium status in hospitalized patients","volume":"65","author":"G Grzych","year":"2019","journal-title":"Clin Chem"},{"issue":"1","key":"pone.0354233.ref006","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.55251","article-title":"Use of albumin-adjusted calcium measurements in clinical practice","volume":"8","author":"N Desgagn\u00e9s","year":"2025","journal-title":"JAMA Netw Open"},{"issue":"8","key":"pone.0354233.ref007","doi-asserted-by":"crossref","first-page":"499","DOI":"10.12788\/jhm.3619","article-title":"Things we do for no reason\u2122: calculating a \u201ccorrected calcium\u201d level","volume":"16","author":"CM Kenny","year":"2021","journal-title":"J Hosp Med"},{"issue":"9","key":"pone.0354233.ref008","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1093\/ndt\/gfn186","article-title":"A formula to predict corrected calcium in haemodialysis patients","volume":"23","author":"A Jain","year":"2008","journal-title":"Nephrol Dial Transplant"},{"issue":"2","key":"pone.0354233.ref009","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1515\/cclm-2019-0568","article-title":"Calcium state estimation by total calcium: the evidence to end the never-ending story","volume":"58","author":"J-D Pekar","year":"2020","journal-title":"Clin Chem Lab Med"},{"issue":"3","key":"pone.0354233.ref010","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.amjsurg.2004.11.017","article-title":"A comparison of corrected serum calcium levels to ionized calcium levels among critically ill surgical patients","volume":"189","author":"MC Byrnes","year":"2005","journal-title":"Am J Surg"},{"issue":"4","key":"pone.0354233.ref011","article-title":"Discrepancies in corrected calcium versus ionised calcium in a geriatric population: an observational study","volume":"53","author":"APSP Suryapranata","year":"2024","journal-title":"Age Ageing"},{"key":"pone.0354233.ref012","doi-asserted-by":"crossref","first-page":"1070443","DOI":"10.3389\/fendo.2023.1070443","article-title":"Derivation and comparison of formulae for the adjustment of total calcium","volume":"14","author":"M Phylactou","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"5","key":"pone.0354233.ref013","doi-asserted-by":"crossref","first-page":"108","DOI":"10.14740\/jem757","article-title":"Total calcium and ionized calcium (pH = 7.4) tests are equal when screening patients for hypercalcemia at admission in the emergency department: a retrospective descriptive study","volume":"11","author":"R Wittenberg","year":"2021","journal-title":"J Endocrinol Metab"},{"issue":"4","key":"pone.0354233.ref014","first-page":"355","article-title":"Overestimation of albumin measured by bromocresol green vs bromocresol purple method: influence of acute-phase globulins","volume":"49","author":"V Garcia Moreira","year":"2018","journal-title":"Lab Med"},{"key":"pone.0354233.ref015","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.cca.2011.01.008","article-title":"Is the accuracy of serum albumin measurements suitable for clinical application of the test?","volume":"412","author":"I Infusino","year":"2011","journal-title":"Clin Chim Acta"},{"issue":"4","key":"pone.0354233.ref016","first-page":"203","article-title":"Bias assessment of general chemistry analytes using commutable samples","volume":"35","author":"G Koerbin","year":"2014","journal-title":"Clin Biochem Rev"},{"key":"pone.0354233.ref017","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1177\/0004563215593561","article-title":"Age and sex variation in serum albumin concentration: an observational study","volume":"53","author":"G Weaving","year":"2016","journal-title":"Ann Clin Biochem"},{"key":"pone.0354233.ref018","doi-asserted-by":"crossref","first-page":"22","DOI":"10.21037\/jlpm-20-60","article-title":"Ionized calcium: analytical challenges and clinical relevance","volume":"5","author":"A Hamroun","year":"2020","journal-title":"J Lab Precis Med"},{"key":"pone.0354233.ref019","doi-asserted-by":"crossref","first-page":"117353","DOI":"10.1016\/j.cca.2023.117353","article-title":"Reconsideration of \u201cAlbumin corrected total calcium\u201d Determinations: potential errors in the Clinical management of disorders of calcium metabolism","volume":"544","author":"SG Albert","year":"2023","journal-title":"Clin Chim Acta"},{"issue":"1","key":"pone.0354233.ref020","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.lers.2024.02.001","article-title":"Identification of clinical subphenotypes of sepsis after laparoscopic surgery","volume":"7","author":"J Yang","year":"2024","journal-title":"Laparosc Endosc Robot Surg"},{"issue":"8","key":"pone.0354233.ref021","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/aje\/kwv254","article-title":"Using big data to emulate a target trial when a randomized trial is not available","volume":"183","author":"MA Hern\u00e1n","year":"2016","journal-title":"Am J Epidemiol"},{"key":"pone.0354233.ref022","article-title":"A comprehensive step-by-step approach for the implementation of target trial emulation: evaluating fluid resuscitation strategies in post-laparoscopic septic shock as an example","author":"J Yang","year":"2025","journal-title":"Laparosc Endosc Robot Surg"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0354233","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:27:43Z","timestamp":1784654863000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0354233"}},"subtitle":[],"editor":[{"given":"Ahmet","family":"\u00c7a\u011flar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":22,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0354233","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}