{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:05:58Z","timestamp":1792436758855,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mineral bone disorders (MBD) are common in sickle cell anemia (SCA). Frequent vaso-occlusive crises (VOC) further impact MBD in children with SCA. We evaluated the prevalence of markers of SCA-related MBD (sMBD) in hospitalized children and assessed the relationship between sMBD and individual mineral abnormalities with kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We prospectively recruited 185 children with SCA hospitalized with a VOC. Serum measures of mineral bone metabolism (calcium, phosphate, parathyroid hormone, 25-hydroxy vitamin D, FGF23, osteopontin) were measured at enrollment. The primary outcome was markers of sMBD defined as a composite of hypocalcemia, hyperphosphatemia, hyperparathyroidism, or deficiency in 25-OH vitamin D. Secondary outcomes included individual abnormalities in mineral metabolism. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines were used to define SCA-associated acute kidney injury (AKI). AKI was further assessed using urine NGAL as a marker of tubular injury. Acute kidney disease (AKD) was defined as a composite of AKI, an eGFR\u2009&amp;lt;\u200990\u2005m\n                      <jats:underline>l<\/jats:underline>\n                      \/min per 1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      using the Cystatin C GFR equation, or evidence of structural injury (positive biomarker test or albuminuria).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The mean age of children was 8.9 years and 41.6% were female. The prevalence of sMBD was 47.6%, with hypocalcemia the most frequent abnormality (29.9%, 55\/184) followed by hyperphosphatemia (20.7%, 38\/184), hyperparathyroidism (8.7%, 16\/185), and vitamin D deficiency (5.4%, 10\/185). There was no association between sMBD and sKDIGO-defined AKI using serial changes in creatinine or when incorporating biomarkers to define AKI. However, the presence of AKD was associated with a 2.01-fold increased odds of sMBD (95% CI 1.05 to 3.83) and was driven by a decrease in eGFR (OR, 2.90 95% CI: 1.59 to 5.29). When evaluating individual mineral abnormalities, hypocalcemia was associated with AKD and low eGFR while hyperparathyroidism was associated with low eGFR, AKI and structural injury. Vitamin D deficiency was associated with structural kidney injury. Vitamin D deficiency, hyperparathryoidism, and increases in FGF23 and osteopontin predicted mortality (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05 for all).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MBD is common among children with SCA hospitalized with VOC. Biomarkers of kidney injury and bone health may help risk stratify children at risk of sMBD. Routine evaluation of sMBD in children with SCA may improve long-term bone health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2022.1078853","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:19:55Z","timestamp":1675333195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Mineral bone disorders and kidney disease in hospitalized children with sickle cell anemia"],"prefix":"10.3389","volume":"10","author":[{"given":"Anthony","family":"Batte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Kasirye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reagan","family":"Baluku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kiguli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kalyesubula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandy C.","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Schwaderer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik A.","family":"Imel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Conroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2018","DOI":"10.1016\/S0140-6736(10)61029-X","article-title":"Sickle-cell disease","volume":"376","author":"Rees","year":"2010","journal-title":"Lancet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle cell disease","volume":"376","author":"Piel","year":"2017","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/j.1365-2141.2005.05476.x","article-title":"Bone involvement in sickle cell disease","volume":"129","author":"Almeida","year":"2005","journal-title":"Br J Haematol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1002\/jbmr.412","article-title":"Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass","volume":"26","author":"Baxter-Jones","year":"2011","journal-title":"J Bone Miner Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1359\/jbmr.1999.14.10.1672","article-title":"A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study","volume":"14","author":"Bailey","year":"1999","journal-title":"J Bone Miner Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1001\/jama.285.6.785","article-title":"Osteoporosis prevention, diagnosis, and therapy","volume":"285","year":"2001","journal-title":"Jama."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1016\/j.jada.2008.06.433","article-title":"High risk of vitamin D deficiency in children with sickle cell disease","volume":"108","author":"Rovner","year":"2008","journal-title":"J Am Diet Assoc"},{"key":"B8","doi-asserted-by":"publisher","first-page":"120","DOI":"10.4314\/wajm.v24i2.28180","article-title":"Serum magnesium, phosphate and calcium in Nigerian children with sickle cell disease","volume":"24","author":"Oladipo","year":"2005","journal-title":"West Afr J Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1177\/000456329303000108","article-title":"Serum calcium, parathyroid hormone, and vitamin D status in children and young adults with sickle cell disease","volume":"30","author":"Mohammed","year":"1993","journal-title":"Ann Clin Biochem"},{"key":"B10","doi-asserted-by":"publisher","first-page":"8352","DOI":"10.1073\/pnas.140021997","article-title":"Phosphate is a specific signal for induction of osteopontin gene expression","volume":"97","author":"Beck","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1093\/qjmed\/95.1.3","article-title":"Osteopontin\u2014a molecule for all seasons","volume":"95","author":"Mazzali","year":"2002","journal-title":"QJM"},{"key":"B12","doi-asserted-by":"publisher","first-page":"S24","DOI":"10.1038\/ki.2011.27","article-title":"Phosphate and FGF-23","volume":"79","author":"J\u00fcppner","year":"2011","journal-title":"Kidney Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-022-02731-9","article-title":"Acute kidney injury in hospitalized children with sickle cell anemia","volume":"23","author":"Batte","year":"2022","journal-title":"BMC Nephrol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.2215\/CJN.01600211","article-title":"Chronic kidney disease and albuminuria in children with sickle cell disease","volume":"6","author":"Yee","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.kisu.2017.04.001","article-title":"KDIGO 2017 Clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) foreword","volume":"7","author":"Wheeler","year":"2017","journal-title":"Kidney Int Suppl (2011)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"635628","DOI":"10.3389\/fped.2020.635628","article-title":"Acute kidney injury and pediatric bone health","volume":"8","author":"Hegde","year":"2020","journal-title":"Front Pediatr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12882-018-1181-1","article-title":"Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes","volume":"20","author":"Yang","year":"2019","journal-title":"BMC Nephrol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1159\/000346815","article-title":"Urine catalytic iron and neutrophil gelatinase-associated lipocalin as companion early markers of acute kidney injury after cardiac surgery: a prospective pilot study","volume":"3","author":"Akrawinthawong","year":"2013","journal-title":"Cardiorenal Med"},{"key":"B19","first-page":"35","volume-title":"Survey sampling","author":"Kish","year":"1965"},{"key":"B20","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s00467-011-2081-9","article-title":"A simple height-independent equation for estimating glomerular filtration rate in children","volume":"27","author":"Pottel","year":"2012","journal-title":"Pediatr Nephrol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1186\/s12882-020-02076-1","article-title":"Methods to estimate baseline creatinine and define acute kidney injury in lean Ugandan children with severe malaria: a prospective cohort study","volume":"21","author":"Batte","year":"2020","journal-title":"BMC Nephrol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nrneph.2015.8","article-title":"Sickle cell disease: renal manifestations and mechanisms","volume":"11","author":"Nath","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1093\/bja\/aes357","article-title":"Novel biomarkers of acute kidney injury and failure: clinical applicability","volume":"109","author":"Martensson","year":"2012","journal-title":"Br J Anaesth"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.2215\/CJN.12851216","article-title":"Biomarkers for diagnosis and prognosis of AKI in children: one size does not fit all","volume":"12","author":"Greenberg","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e2019209","DOI":"10.1001\/jamanetworkopen.2020.19209","article-title":"Recommendations on acute kidney injury biomarkers from the acute disease quality initiative consensus conference: a consensus statement","volume":"3","author":"Ostermann","year":"2020","journal-title":"JAMA Netw Open."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jcrc.2019.05.017","article-title":"Integration of urinary neutrophil gelatinase-associated lipocalin with serum creatinine delineates acute kidney injury phenotypes in critically ill children","volume":"53","author":"Stanski","year":"2019","journal-title":"J Crit Care"},{"key":"B27","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.kint.2020.10.047","article-title":"Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease","volume":"99","author":"Pierce","year":"2021","journal-title":"Kidney Int"},{"key":"B28","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/kisup.2012.1","article-title":"KDIGO clinical practice guideline for acute kidney injury","volume":"2","year":"2012","journal-title":"Kidney Int"},{"key":"B29","volume-title":"Mosby's diagnostic and laboratory tests","author":"Pagana","year":"2021"},{"key":"B30","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1373\/clinchem.2011.177741","article-title":"Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children","volume":"58","author":"Colantonio","year":"2012","journal-title":"Clin Chem"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/kisup.2012.73","article-title":"KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","year":"2013","journal-title":"Kidney Int (Supplement)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1210\/jc.2015-2175","article-title":"Global consensus recommendations on prevention and management of nutritional rickets","volume":"101","author":"Munns","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B33","first-page":"169","article-title":"Chronic kidney disease: mineral and bone disorder in children","author":"Wesseling-Perry","year":"2013","journal-title":"Elsevier"},{"key":"B34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/1750-1172-9-67","article-title":"First evidence of subclinical renal tubular injury during sickle-cell crisis","volume":"9","author":"Audard","year":"2014","journal-title":"Orphanet J Rare Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s12916-021-01985-8","article-title":"Prevalence and predictors of vitamin D deficiency in young African children","volume":"19","author":"Mogire","year":"2021","journal-title":"BMC Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1172\/JCI116857","article-title":"Effects of deoxygenation on active and passive Ca2\u2009+\u2009transport and on the cytoplasmic Ca2+levels of sickle cell anemia red cells","volume":"92","author":"Etzion","year":"1993","journal-title":"J Clin Invest"},{"key":"B37","article-title":"Hyperphosphatemia","volume-title":"Statpearls","author":"Goyal","year":"2022"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1002\/pbc.25188","article-title":"Abnormalities in renal tubular phosphate handling in children with sickle cell disease","volume":"61","author":"Raj","year":"2014","journal-title":"Pediatr Blood Cancer"},{"key":"B39","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/j.1365-2141.2011.08853.x","article-title":"Sickle cell nephropathy\u2014a practical approach","volume":"155","author":"Sharpe","year":"2011","journal-title":"Br J Haematol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e537","DOI":"10.1542\/peds.2006-0337","article-title":"Primary hyperparathyroidism mimicking vaso-occlusive crises in sickle cell disease","volume":"118","author":"Krishnamoorthy","year":"2006","journal-title":"Pediatrics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3390\/jcm9020308","article-title":"Primary hyperparathyroidism in sickle cell disease: an unknown complication of the disease in adulthood","volume":"9","author":"Denoix","year":"2020","journal-title":"J Clin Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.kint.2015.12.035","article-title":"Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery","volume":"89","author":"Leaf","year":"2016","journal-title":"Kidney Int"},{"key":"B43","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cyto.2017.12.024","article-title":"C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality","volume":"103","author":"Rygasiewicz","year":"2018","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1681\/ASN.2016080836","article-title":"Fibroblast growth factor 23 levels associate with AKI and death in critical illness","volume":"28","author":"Leaf","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B45","doi-asserted-by":"publisher","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":"B46","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1182\/blood.V126.23.2171.2171","article-title":"Plasma FGF23 is a biomarker for left ventricular hypertrophy and mortality in adults with sickle cell anemia chronic kidney disease","volume":"126","author":"Liu","year":"2015","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ejim.2020.04.035","article-title":"Early osteopontin levels predict mortality in patients with septic shock","volume":"78","author":"Carbone","year":"2020","journal-title":"Eur J Intern Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1186\/s13054-015-0988-4","article-title":"Persistently elevated osteopontin serum levels predict mortality in critically ill patients","volume":"19","author":"Roderburg","year":"2015","journal-title":"Crit Care."},{"key":"B49","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1093\/ndt\/gfq498","article-title":"Osteopontin predicts survival in critically ill patients with acute kidney injury","volume":"26","author":"Lorenzen","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"B50","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1097\/SHK.0000000000000721","article-title":"Osteopontin blockade attenuates renal injury after ischemia reperfusion by inhibiting NK cell infiltration","volume":"47","author":"Cen","year":"2017","journal-title":"Shock"},{"key":"B51","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1161\/ATVBAHA.118.311577","article-title":"Osteopontin in vascular disease: friend or foe?","volume":"39","author":"Lok","year":"2019","journal-title":"Arterioscler, Thromb, Vasc Biol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"eabm5900","DOI":"10.1126\/sciadv.abm5900","article-title":"Identification of kidney injury\u2013released circulating osteopontin as causal agent of respiratory failure","volume":"8","author":"Khamissi","year":"2022","journal-title":"Sci Adv"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1038\/sj.ki.5002729","article-title":"Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review","volume":"73","author":"Coca","year":"2008","journal-title":"Kidney Int"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1078853\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T10:20:00Z","timestamp":1675333200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2022.1078853\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,2]]},"references-count":53,"alternative-id":["10.3389\/fped.2022.1078853"],"URL":"https:\/\/doi.org\/10.3389\/fped.2022.1078853","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,2]]},"article-number":"1078853"}}