{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:55:09Z","timestamp":1781585709545,"version":"3.54.5"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"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. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To describe the severity, timing, etiology, and outcome of ionized hypocalcemia in a population of dogs and cats with all-cause azotemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Medical records of dogs and cats with concurrent ionized hypocalcemia and azotemia, in which ionized calcium (iCa) was measured within 24\u202fh of serum biochemistry testing were retrospectively reviewed from a single institution over a 10-year period (January 1st, 2014, to December 31st, 2023). Ionized hypocalcemia was defined as iCa\u202f&amp;lt;\u202f1.21\u202fmmol\/L in cats and &amp;lt; 1.30\u202fmmol\/L in dogs. Moderate hypocalcemia was defined as iCa\u202f&amp;lt;\u202f1.00\u202fmmol\/L and severe hypocalcemia as iCa\u202f&amp;lt;\u202f0.75\u202fmmol\/L. Azotemia was defined as a creatinine concentration \u2265 141\u202f\u03bcmol\/L (1.7\u202fmg\/dL). The primary cause of azotemia was determined by review of the medical record, and diagnostic criteria for acute kidney injury and chronic kidney disease were based on International Renal Interest Society guidelines. Data extracted included signalment, clinicopathologic variables, etiology of azotemia, and outcome. Outcome was defined as survival to discharge or non-survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      302 cats and 646 dogs met the inclusion criteria. Ionized hypocalcemia was mild in 229\/302 (75.8%) cats and 551\/646 (85.3%) dogs, moderate in 69\/302 (22.8%) cats and 83\/646 (12.8%) dogs, and severe in 4\/302 (1.3%) cats and 12\/646 (1.9%) dogs. The lowest iCa occurred within 48\u202fh of admission in 155\/223 (69.5%) cats and 338\/465 (72.7%) dogs hospitalized for at least 48\u202fh. In cats, both renal (176\/302, 58.3%) and postrenal (126\/302, 41.7%) causes of azotemia were common, whereas renal causes predominated in dogs (602\/646, 93.2%). Inflammatory\/ischemic etiologies were the most common cause of acute kidney injury in both cats (54\/90, 60.0%) and dogs (230\/383, 60.1%). Ionized calcium showed weak correlations with blood phosphorus (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.36 cats, \u22120.31 dogs), pH (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f0.21 cats, 0.15 dogs), and creatinine concentrations (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.30 cats, \u22120.26 dogs) (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Clinical signs potentially attributable to hypocalcemia were reported in 9\/16 (56.3%) severely hypocalcemic patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ionized hypocalcemia in azotemic cats and dogs is generally mild and occurs early in hospitalization. It is only weakly associated with higher blood phosphorus and creatinine concentrations and lower blood pH. Routine monitoring of iCa in azotemic patients is recommended. These findings may not be generalizable to all azotemic patients, as iCa measurement was performed at the discretion of the attending clinician.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1847148","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:27:52Z","timestamp":1781584072000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Severity, etiology and outcomes of ionized hypocalcemia in azotemic cats and dogs"],"prefix":"10.3389","volume":"13","author":[{"given":"Helen S.","family":"Philp","sequence":"first","affiliation":[{"name":"Department of Veterinary Surgical and Radiological Sciences, UC Davis Weill School of Veterinary Medicine, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgical and Radiological Sciences, UC Davis Weill School of Veterinary Medicine, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Hopper","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgical and Radiological Sciences, UC Davis Weill School of Veterinary Medicine, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fvets.2017.00135","article-title":"Electrolyte disturbances are associated with non-survival in dogs: a multivariable analysis","volume":"4","author":"Goggs","year":"2017","journal-title":"Front Vet Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.jcrc.2021.07.008","article-title":"Hypocalcemia is associated with hypotension during CRRT: a secondary analysis of the acute renal failure trial network study","volume":"65","author":"Kelly","year":"2021","journal-title":"J Crit Care"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1759091415578050","DOI":"10.1177\/1759091415578050","article-title":"Hypocalcemia-induced seizure: demystifying the calcium paradox","volume":"7","author":"Han","year":"2015","journal-title":"ASN Neuro"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3390\/medicina55050204","article-title":"The effect of serum calcium levels on uremic encephalopathy in patients with acute kidney injury in the emergency department","volume":"55","author":"Akman","year":"2019","journal-title":"Medicina (Kaunas)"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1177\/1098612X17743564","article-title":"Multivariable analysis of the association between electrolyte disturbances and mortality in cats","volume":"20","author":"Goggs","year":"2018","journal-title":"J Feline Med Surg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"12316","DOI":"10.1038\/s41598-020-69405-0","article-title":"Impact of admission serum ionized calcium levels on risk of acute kidney injury in hospitalized patients","volume":"10","author":"Thongprayoon","year":"2020","journal-title":"Sci Rep"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fvets.2019.00276","article-title":"Severity of ionized hypercalcemia and hypocalcemia is associated with etiology in dogs and cats","volume":"6","author":"Coady","year":"2019","journal-title":"Front Vet Sci."},{"key":"ref8","first-page":"209","article-title":"Prediction of serum ionized calcium concentration by serum total calcium measurement in cats","volume":"74","author":"Schenck","year":"2010","journal-title":"Can J Vet Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1111\/j.1939-165X.2006.tb00161.x","article-title":"Serum ionized calcium in dogs with chronic renal failure and metabolic acidosis","volume":"35","author":"Kogika","year":"2006","journal-title":"Vet Clin Pathol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/jvim.14653","article-title":"Association of vitamin D metabolites with parathyroid hormone, fibroblast growth factor-23, calcium, and phosphorus in dogs with various stages of chronic kidney disease","volume":"31","author":"Parker","year":"2017","journal-title":"J Vet Intern Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.2460\/ajvr.2005.66.1330","article-title":"Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs","volume":"66","author":"Schenck","year":"2005","journal-title":"Am J Vet Res"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1111\/j.1534-6935.2003.00100.x","article-title":"Characterization of clinical characteristics, electrolytes, acid\u2013base, and renal parameters in male cats with urethral obstruction","volume":"13","author":"Lee","year":"2003","journal-title":"J Vet Emerg Crit Care (San Antonio)"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.2460\/javma.1997.211.11.1392","article-title":"Concentration of ionized calcium in plasma from cats with urethral obstruction","volume":"211","author":"Drobatz","year":"1997","journal-title":"J Am Vet Med Assoc"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jfms.2010.10.006","article-title":"Urethral obstruction in cats: predisposing factors, clinical and clinicopathological characteristics and prognosis","volume":"13","author":"Segev","year":"2011","journal-title":"J Feline Med Surg"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.cca.2019.03.1616","article-title":"Association of serum total and ionized calcium with all-cause mortality in critically ill patients with acute kidney injury","volume":"494","author":"Wang","year":"2019","journal-title":"Clin Chim Acta"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.3109\/0886022X.2013.828258","article-title":"Effect of ionized serum calcium on outcomes in acute kidney injury needing renal replacement therapy: secondary analysis of the acute renal failure trial network study","volume":"35","author":"Afshinnia","year":"2013","journal-title":"Ren Fail"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1939-1676.2008.0063.x","article-title":"A novel clinical scoring system for outcome prediction in dogs with acute kidney injury managed by hemodialysis","volume":"22","author":"Segev","year":"2008","journal-title":"J Vet Intern Med"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1111\/jvim.13930","article-title":"Validation of a clinical scoring system for outcome prediction in dogs with acute kidney injury managed by hemodialysis","volume":"30","author":"Segev","year":"2016","journal-title":"J Vet Intern Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"728","DOI":"10.2460\/javma.232.5.728","article-title":"Acute intrinsic renal failure in cats: 32 cases (1997\u20132004)","volume":"232","author":"Worwag","year":"2008","journal-title":"J Am Vet Med Assoc"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.cvsm.2013.07.008","article-title":"Hypocalcemia of critical illness in dogs and cats","volume":"43","author":"Holowaychuk","year":"2013","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1111\/vec.12032","article-title":"The role of phosphorus in the pathophysiology of chronic kidney disease","volume":"23","author":"Geddes","year":"2013","journal-title":"J Vet Emerg Crit Care (San Antonio)"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.cvsm.2016.10.017","article-title":"A quick reference on hypocalcemia","volume":"47","author":"de Brito Galv\u00e3o","year":"2017","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/9781118785546.ch49","volume-title":"Nephrology and Urology of Small Animals","author":"Cowgill","year":"2011"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/ki.1974.62","article-title":"Divalent ion metabolism in patients with acute renal failure: studies on the mechanism of hypocalcemia","volume":"5","author":"Massry","year":"1974","journal-title":"Kidney Int"},{"key":"ref25","year":"2024"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3390\/vetsci7040147","article-title":"How ultrasound can be useful for staging chronic kidney disease in dogs: ultrasound findings in 855 cases","volume":"7","author":"Perondi","year":"2020","journal-title":"Vet Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/jvim.16375","article-title":"Acute kidney injury in dogs: etiology, clinical and clinicopathologic findings, prognostic markers, and outcome","volume":"36","author":"Rimer","year":"2022","journal-title":"J Vet Intern Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.tvjl.2019.02.008","article-title":"International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats","volume":"247","author":"Weese","year":"2019","journal-title":"Vet J"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1111\/jvim.16903","article-title":"Updated ACVIM consensus statement on leptospirosis in dogs","volume":"37","author":"Sykes","year":"2023","journal-title":"J Vet Intern Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.cvsm.2016.06.009","article-title":"Management of proteinuria in dogs and cats with chronic kidney disease","volume":"46","author":"Vaden","year":"2016","journal-title":"Vet Clin North Am Small Anim Pract"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/vec.13441","article-title":"Determination of reference intervals of venous blood gas and acid\u2013base parameters in clinically healthy awake cats","volume":"35","author":"Preteseille","year":"2025","journal-title":"J Vet Emerg Crit Care (San Antonio)"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"106068","DOI":"10.1016\/j.tvjl.2024.106068","article-title":"International renal interest society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs","volume":"305","author":"Segev","year":"2024","journal-title":"Vet J"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation coefficients: appropriate use and interpretation","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth Analg"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.21608\/zumj.2024.260994.3096","article-title":"Hypocalcemia in acute kidney injury patients admitted to intensive care unit and its relation to clinical outcome","author":"Samir","year":"2024","journal-title":"Zagazig Univ Med J"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"4418","DOI":"10.1038\/s41598-020-61459-4","article-title":"Hidden hypocalcemia as a risk factor for cardiovascular events and all-cause mortality among patients undergoing incident hemodialysis","volume":"10","author":"Yamaguchi","year":"2020","journal-title":"Sci Rep"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/1471-2369-15-183","article-title":"Low serum calcium is associated with poor renal outcomes in chronic kidney disease stages 3\u20134 patients","volume":"15","author":"Lim","year":"2014","journal-title":"BMC Nephrol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"353","DOI":"10.51253\/pafmj.v73i2.6534","article-title":"Evaluation of adjusted calcium levels in patients of chronic renal failure with hypoalbuminemia","volume":"73","author":"Habib","year":"2023","journal-title":"Pak Armed Forces Med J"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/j.1939-1676.1997.tb00074.x","article-title":"A retrospective case-control of acute renal failure in 99 dogs","volume":"11","author":"Vaden","year":"1997","journal-title":"J Vet Intern Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/jvim.14867","article-title":"Regional citrate anticoagulation for intermittent hemodialysis in dogs","volume":"32","author":"Francey","year":"2018","journal-title":"J Vet Intern Med"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1186\/s40064-015-1387-7","article-title":"Calcium supplementation improves clinical outcome in intensive care unit patients: a propensity score matched analysis of a large clinical database MIMIC-II","volume":"4","author":"Zhang","year":"2015","journal-title":"Springerplus"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1097\/MCC.0000000000001059","article-title":"Management of hypocalcaemia in the critically ill","volume":"29","author":"Melchers","year":"2023","journal-title":"Curr Opin Crit Care"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1847148\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:27:54Z","timestamp":1781584074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1847148\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":41,"alternative-id":["10.3389\/fvets.2026.1847148"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1847148","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"article-number":"1847148"}}