{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:06:37Z","timestamp":1793909197399,"version":"4.8.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Milk-alkali syndrome, which is characterized by hypercalcemia, metabolic alkalosis, and renal dysfunction, typically results from the ingestion of large amounts of calcium and absorbable alkaline products. However, these symptoms can also manifest when alkalosis and calcium loading occur simultaneously, owing to other factors. We report a case of milk-alkali syndrome caused by loop-diuretic-induced alkaline load and polypharmacy in an 85-year-old Japanese woman with multiple comorbidities, including osteoporosis, hypertension, type 2 diabetes, dyslipidemia, and Parkinson\u2019s disease. The patient regularly took 14 drugs, including calcium L-aspartate, eldecalcitol, celecoxib, and a fixed-dose combination of losartan and hydrochlorothiazide. Immediately before admission, furosemide was administered for the treatment of edema. The patient presented with chest discomfort, general malaise, and clinical signs of dehydration, hypercalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia, accompanied by electrocardiogram abnormalities, renal dysfunction, and chloride-resistant metabolic alkalosis. The hypercalcemia was specifically induced by calcium L-aspartate and eldecalcitol. The hypomagnesaemia and hypophosphatemia were caused by diuretics and hypercalcemia. Thus, all the oral medications were discontinued, and rehydration and electrolyte correction therapy were administered. The final diagnosis was milk-alkali syndrome caused by the concomitant use of loop diuretics and other medications, without absorbable alkaline preparation use. This case underscores the importance of considering drug-related factors, checking concomitant medications, and being aware of the benefits, harmful effects, and side effects of polypharmacy in older adults with multimorbidity.<\/jats:p>","DOI":"10.3390\/medicina59071345","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:57:30Z","timestamp":1690160250000},"page":"1345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Case of Milk-Alkali Syndrome Caused by Diuretic-Induced Alkalosis and Polypharmacy"],"prefix":"10.3390","volume":"59","author":[{"given":"Naoya","family":"Mizutani","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Tamba 669-3495, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Goda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Tamba 669-3495, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-6605","authenticated-orcid":false,"given":"Tsuneaki","family":"Kenzaka","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hyogo Prefectural Tamba Medical Center, Tamba 669-3495, Japan"},{"name":"Division of Community Medicine and Career Development, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2169\/internalmedicine.49.2601","article-title":"Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide","volume":"49","author":"Satoh","year":"2010","journal-title":"Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1445-5994.2004.00611.x","article-title":"Milk-alkali syndrome: Broadening the spectrum of causes to allow early recognition","volume":"34","author":"Kleinig","year":"2004","journal-title":"Intern. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1053\/j.ajkd.2008.11.015","article-title":"Calcium-alkali syndrome due to vitamin D administration and magnesium oxide administration","volume":"53","author":"Hanada","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"306","DOI":"10.2215\/CJN.10330818","article-title":"The use of selected urine chemistries in the diagnosis of kidney disorders","volume":"14","author":"Palmer","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1574886308666140109112730","article-title":"Diuretic-associated electrolyte disorders in the elderly: Risk factors, impact, management and prevention","volume":"9","author":"Khow","year":"2014","journal-title":"Curr. Drug Saf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3109\/00365515909060464","article-title":"Effect of chlorothiazide and hydrochlorothiazide on the excretion of calcium in urine","volume":"11","author":"Lamberg","year":"1959","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1056\/NEJM196907102810201","article-title":"Chlorothiazide-induced hypercalcemia in juvenile osteoporosis and hyperparathyrxoidism","volume":"281","author":"Parfitt","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"F973","article-title":"Peptide hormone effects on urinary acidification and acid-base balance: PTH, ADH, and glucagon","volume":"256","author":"Paillard","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1046\/j.1523-1755.2000.00323.x","article-title":"Chronic effect of parathyroid hormone on NHE3 expression in rat renal proximal tubules","volume":"58","author":"Girardi","year":"2000","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/ki.1979.67","article-title":"Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney","volume":"15","author":"Sutton","year":"1979","journal-title":"Kidney Int."},{"key":"ref_11","first-page":"F394","article-title":"Urine HCO3\u2212 augments renal Ca2+ absorption independent of systemic acid-base changes","volume":"238","author":"Peraino","year":"1980","journal-title":"Am. J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/j.0954-6820.1963.tb17426.x","article-title":"The milk-alkali syndrome. A report of three illustrative cases and a review of the literature","volume":"173","author":"Punsar","year":"1963","journal-title":"Acta Med. Scand."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1093\/ndt\/14.3.782","article-title":"Iatrogenic hypercalcaemia, hypokalaemia and metabolic alkalosis in a lady with vena cava thrombosis\u2014Beware of overzealous diuretic treatment","volume":"14","author":"Schmaldienst","year":"1999","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5049\/EBP.2010.8.2.92","article-title":"Hypercalcemia associated with acute kidney injury and metabolic alkalosis","volume":"8","author":"Jeong","year":"2010","journal-title":"Electrolyte Blood Press."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.4065\/84.6.562-b","article-title":"Use of furosemide for milk-alkali syndrome","volume":"84","author":"Homler","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/j.1365-2265.2005.02383.x","article-title":"Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients","volume":"63","author":"Picolos","year":"2005","journal-title":"Clin. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3325\/cmj.2019.60.42","article-title":"Hypercalcemia secondary to excessive self-medication with antacids causing acute pancreatitis: A case report","volume":"60","author":"Vassallo","year":"2019","journal-title":"Croat. Med. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2324709620922724","DOI":"10.1177\/2324709620922724","article-title":"Over-the-counter drug causing acute pancreatitis","volume":"8","author":"Parvataneni","year":"2020","journal-title":"J. Investig. Med. High Impact Case Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100278","DOI":"10.1016\/j.bonr.2020.100278","article-title":"A 39-year-old woman with milk-alkali syndrome complicated by posterior reversible encephalopathy syndrome","volume":"12","author":"Vu","year":"2020","journal-title":"Bone Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"The 2019 American Geriatrics Society Beers Criteria\u00ae Update Expert Panel (2019). American Geriatrics Society 2019 updated AGS beers Criteria\u00ae for potentially inappropriate medication use in older adults. J. Am. Geriatr. Soc., 67, 674\u2013694.","DOI":"10.1111\/jgs.15767"},{"key":"ref_21","first-page":"213","article-title":"STOPP\/START Criteria for Potentially Inappropriate Prescribing in Older People: Version 2","volume":"44","author":"Byrne","year":"2015","journal-title":"Age Ageing"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.14442\/general.15.117","article-title":"Risk factors and specific prescriptions related to inappropriate prescribing among Japanese elderly home care patients","volume":"15","author":"Hamano","year":"2014","journal-title":"Gen. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bories, M., Bouzill\u00e9, G., Cuggia, M., and Le Corre, P. (2021). Drug-drug interactions in elderly patients with potentially inappropriate medications in primary care, nursing home and hospital settings: A systematic review and a preliminary study. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020266"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.14442\/general.15.110","article-title":"Polypharmacy and adverse drug events leading to acute care hospitalization in Japanese elderly","volume":"15","author":"Fushiki","year":"2014","journal-title":"Gen. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s40266-018-0554-2","article-title":"International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP): Position statement and 10 recommendations for action","volume":"35","author":"Mangin","year":"2018","journal-title":"Drugs Aging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1007\/s11606-020-06089-2","article-title":"Deprescribing for community-dwelling older adults: A systematic review and meta-analysis","volume":"35","author":"Bloomfield","year":"2020","journal-title":"J. Gen. Intern. Med."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/7\/1345\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:16:58Z","timestamp":1760127418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/7\/1345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,22]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["medicina59071345"],"URL":"https:\/\/doi.org\/10.3390\/medicina59071345","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,22]]}}}