{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:22:06Z","timestamp":1790803326404,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007338","name":"Barnes-Jewish Hospital Foundation","doi-asserted-by":"publisher","award":["CTRFP1621"],"award-info":[{"award-number":["CTRFP1621"]}],"id":[{"id":"10.13039\/100007338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS\/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 \u00b5M. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) \u00b5M], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae097","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T13:11:17Z","timestamp":1722604277000},"page":"1172-1181","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Utility of LC-MS\/MS for Blood Myo-Inositol in Patients with Acute Kidney Injury and Chronic Kidney Disease"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-2129","authenticated-orcid":false,"given":"Catherine L","family":"Omosule","sequence":"first","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor J","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Herries","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Zaydman","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7169-3850","authenticated-orcid":false,"given":"Christopher","family":"Farnsworth","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Ladenson","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J","family":"Dietzen","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"},{"name":"Department of Pediatrics, Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P","family":"Gaut","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University School of Medicine , St. Louis, MO , United States"},{"name":"Department of Medicine (Nephrology), Washington University School of Medicine , St. Louis, MO , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"2024090223525904200_hvae097-B1","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1681\/ASN.2004090740","article-title":"Acute kidney injury, mortality, length of stay, and costs in hospitalized patients","volume":"16","author":"Chertow","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B2","doi-asserted-by":"crossref","first-page":"13225","DOI":"10.1038\/s41598-022-17599-w","article-title":"Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury","volume":"12","author":"Kakkanattu","year":"2022","journal-title":"Sci Rep"},{"key":"2024090223525904200_hvae097-B3","first-page":"1","article-title":"KDIGO clinical practice guideline for acute kidney injury","volume":"2","author":"Acute Kidney Injury Work Group","year":"2012","journal-title":"Kidney Inter Suppl"},{"key":"2024090223525904200_hvae097-B4","author":"KDIGO"},{"key":"2024090223525904200_hvae097-B5","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1373\/clinchem.2013.212993","article-title":"Development of an immunoassay for the kidney specific protein myo-inositol oxygenase, a potential biomarker of acute kidney injury","volume":"60","author":"Gaut","year":"2014","journal-title":"Clin Chem"},{"key":"2024090223525904200_hvae097-B6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/j.ajkd.2012.12.022","article-title":"Biomarkers in nephrology","volume":"62","author":"McMahon","year":"2013","journal-title":"Am J Kidney Dis"},{"key":"2024090223525904200_hvae097-B7","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1681\/ASN.2016070744","article-title":"Beneficial effects of myo-inositol oxygenase deficiency in cisplatin-induced AKI","volume":"28","author":"Dutta","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B8","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/aas.14100","article-title":"Acute kidney injury in intensive care patients: incidence, time course, and risk factors","volume":"66","author":"Mo","year":"2022","journal-title":"Acta Anaesthesiol Scand"},{"key":"2024090223525904200_hvae097-B9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000519536","article-title":"Under-recognition of acute kidney injury after cardiac surgery in the ICU impedes early detection and prevention","volume":"47","author":"Schanz","year":"2021","journal-title":"Kidney Blood Press Res"},{"key":"2024090223525904200_hvae097-B10","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00134-023-07138-0","article-title":"Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study","volume":"49","author":"White","year":"2023","journal-title":"Intensive Care Med"},{"key":"2024090223525904200_hvae097-B11","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2215\/CJN.04971107","article-title":"Evaluation and initial management of acute kidney injury","volume":"3","author":"Himmelfarb","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B12","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1093\/jalm\/jfab020","article-title":"AACC guidance document on laboratory investigation of acute kidney injury","volume":"6","author":"El-Khoury","year":"2021","journal-title":"J Appl Lab Med"},{"key":"2024090223525904200_hvae097-B13","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.2215\/CJN.15341121","article-title":"Low-flow acute kidney injury: the pathophysiology of prerenal azotemia, abdominal compartment syndrome, and obstructive uropathy","volume":"17","author":"Molitoris","year":"2022","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13054-022-04121-x","article-title":"Subphenotypes in acute kidney injury: a narrative review","volume":"26","author":"Vaara","year":"2022","journal-title":"Crit Care"},{"key":"2024090223525904200_hvae097-B15","doi-asserted-by":"crossref","first-page":"717","DOI":"10.2215\/CJN.14181021","article-title":"Overview of diagnostic criteria and epidemiology of acute kidney injury and acute kidney disease in the critically ill patient","volume":"17","author":"Birkelo","year":"2022","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0021-9258(18)70684-4","article-title":"Biochemical studies on inositol. IV. Conversion of inositol to glucuronic acid by rat kidney extracts","volume":"228","author":"Charalampous","year":"1957","journal-title":"J Biol Chem"},{"key":"2024090223525904200_hvae097-B17","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.2337\/db19-0935","article-title":"Myo-inositol oxygenase (MIOX) overexpression drives the progression of renal tubulointerstitial injury in diabetes","volume":"69","author":"Sharma","year":"2020","journal-title":"Diabetes"},{"key":"2024090223525904200_hvae097-B18","doi-asserted-by":"crossref","first-page":"8433","DOI":"10.3390\/ijms22168433","article-title":"Melatonin and myo-inositol: supporting reproduction from the oocyte to birth","volume":"22","author":"Russo","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2024090223525904200_hvae097-B19","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1002\/bmc.3470","article-title":"Quantification of myo-inositol, 1,5-anhydro-D-sorbitol, and D-chiro-inositol using high-performance liquid chromatography with electrochemical detection in very small volume clinical samples","volume":"29","author":"Schimpf","year":"2015","journal-title":"Biomed Chromatogr"},{"key":"2024090223525904200_hvae097-B20","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1016\/j.jchromb.2011.07.043","article-title":"Quantitative analysis of myo-inositol in urine, blood and nutritional supplements by high-performance liquid chromatography tandem mass spectrometry","volume":"879","author":"Leung","year":"2011","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2024090223525904200_hvae097-B21","doi-asserted-by":"crossref","first-page":"077","DOI":"10.4172\/2161-0444.1000246","article-title":"Inositol analysis by HPLC and its stability in scavenged sample conditions","volume":"5","author":"Ward","year":"2015","journal-title":"Med Chem (Los Angeles)"},{"key":"2024090223525904200_hvae097-B22","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1471-2105-7-123","article-title":"Detecting outliers when fitting data with nonlinear regression\u2014a new method based on robust nonlinear regression and the false discovery rate","volume":"7","author":"Motulsky","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2024090223525904200_hvae097-B23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4103\/aca.ACA_157_18","article-title":"Descriptive statistics and normality tests for statistical data","volume":"22","author":"Mishra","year":"2019","journal-title":"Ann Card Anaesth"},{"key":"2024090223525904200_hvae097-B24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1440-1797.2010.01291.x","article-title":"Functional renal reserve capacity in different stages of chronic kidney disease","volume":"15","author":"Barai","year":"2010","journal-title":"Nephrology"},{"key":"2024090223525904200_hvae097-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/jomb-2017-0027","article-title":"Myo-inositol oxygenase as a novel marker in the diagnosis of acute kidney injury","volume":"37","author":"Mertoglu","year":"2018","journal-title":"J Med Biochem"},{"key":"2024090223525904200_hvae097-B26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.33176\/AACB-18-00017","article-title":"Kidney injury biomarkers in an academic hospital setting: where are we now?","volume":"40","author":"van Duijl","year":"2019","journal-title":"Clin Biochem Rev"},{"key":"2024090223525904200_hvae097-B27","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0140-6736(05)74811-X","article-title":"Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery","volume":"365","author":"Mishra","year":"2005","journal-title":"Lancet"},{"key":"2024090223525904200_hvae097-B28","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1186\/cc6192","article-title":"Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study","volume":"11","author":"Dent","year":"2007","journal-title":"Crit Care Lond Engl"},{"key":"2024090223525904200_hvae097-B29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1053\/j.ackd.2008.04.003","article-title":"Biomarkers of acute kidney injury","volume":"15","author":"Edelstein","year":"2008","journal-title":"Adv Chronic Kidney Dis"},{"key":"2024090223525904200_hvae097-B30","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000268955","article-title":"The association of African ancestry and elevated creatinine in the coronary artery risk development in young adults (CARDIA) study","volume":"31","author":"Peralta","year":"2010","journal-title":"Am J Nephrol"},{"key":"2024090223525904200_hvae097-B31","first-page":"1","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","author":"Improving Global Outcomes (KDIGO) CKD Work Group","year":"2013","journal-title":"Kidney Int Suppl"},{"key":"2024090223525904200_hvae097-B32","doi-asserted-by":"crossref","first-page":"e1159","DOI":"10.1016\/S2214-109X(22)00239-X","article-title":"Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study","volume":"10","author":"Fabian","year":"2022","journal-title":"Lancet Glob Health"},{"key":"2024090223525904200_hvae097-B33","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.2215\/CJN.12791019","article-title":"Kidney disease, race, and GFR estimation","volume":"15","author":"Levey","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"2024090223525904200_hvae097-B34","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1053\/j.ajkd.2021.08.003","article-title":"A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease","volume":"79","author":"Delgado","year":"2022","journal-title":"Am J Kidney Dis"},{"key":"2024090223525904200_hvae097-B35","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/jalm\/jfad022","article-title":"AACC\/NKF guidance document on improving equity in chronic kidney disease care","volume":"8","author":"Pierre","year":"2023","journal-title":"J Appl Lab Med"},{"key":"2024090223525904200_hvae097-B36","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1172\/JCI108052","article-title":"Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes","volume":"55","author":"Greene","year":"1975","journal-title":"J Clin Invest"},{"key":"2024090223525904200_hvae097-B37","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1176\/ajp.154.8.1148","article-title":"Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder","volume":"154","author":"Shimon","year":"1997","journal-title":"Am J Psychiatry"},{"key":"2024090223525904200_hvae097-B38","first-page":"537","article-title":"The combined therapy myo-inositol plus D-chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients","volume":"17","author":"Minozzi","year":"2013","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2024090223525904200_hvae097-B39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/01.wad.0000213809.12553.fc","article-title":"Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging","volume":"20","author":"Zhu","year":"2006","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2024090223525904200_hvae097-B40","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.3389\/fphar.2019.01172","article-title":"Myo-inositol and its derivatives: their emerging role in the treatment of human diseases","volume":"10","author":"Chhetri","year":"2019","journal-title":"Front Pharmacol"},{"key":"2024090223525904200_hvae097-B41","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/ajkd.2002.34487","article-title":"Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis","volume":"40","author":"Dharnidharka","year":"2002","journal-title":"Am J Kidney Dis"},{"key":"2024090223525904200_hvae097-B42","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/096721090201000501","article-title":"The effect of age on serum creatinine levels in an aging population: relevance to vascular surgery","volume":"10","author":"Tiao","year":"2002","journal-title":"Cardiovasc Surg"},{"key":"2024090223525904200_hvae097-B43","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/ageing\/24.2.142","article-title":"Serum creatinine levels in older adults: relationship with health status and medications","volume":"24","author":"Salive","year":"1995","journal-title":"Age Ageing"},{"key":"2024090223525904200_hvae097-B44","doi-asserted-by":"crossref","first-page":"e21866","DOI":"10.1016\/j.heliyon.2023.e21866","article-title":"Muscle mass has a greater impact on serum creatinine levels in older males than in females","volume":"9","author":"Yim","year":"2023","journal-title":"Heliyon"},{"key":"2024090223525904200_hvae097-B45","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/00365590310015750","article-title":"Renal function in the elderly (&gt;70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance","volume":"38","author":"Fehrman-Ekholm","year":"2004","journal-title":"Scand J Urol Nephrol"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/70\/9\/1172\/58997259\/hvae097.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/70\/9\/1172\/58997259\/hvae097.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:41:07Z","timestamp":1725324067000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/70\/9\/1172\/7726119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,2]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,8,2]]},"published-print":{"date-parts":[[2024,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvae097","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,9]]},"published":{"date-parts":[[2024,8,2]]}}}