{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:47:47Z","timestamp":1789764467245,"version":"4.0.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Nephrol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to \u22653.5\u2009mEq\/L or remained &lt;\u20093.5\u2009mEq\/L, respectively) before or after L-AMB treatment initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%;<jats:italic>P<\/jats:italic>\u2009=\u20090.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%;<jats:italic>P<\/jats:italic>\u2009=\u20090.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584\u20132.852,<jats:italic>P<\/jats:italic>\u2009=\u20090.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400\u20132.275,<jats:italic>P<\/jats:italic>\u2009=\u20090.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (<jats:italic>P<\/jats:italic>\u2009=\u20090.358).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12882-021-02450-7","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T08:02:55Z","timestamp":1625040175000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Association between potassium supplementation and the occurrence of acute kidney injury in patients with hypokalemia administered liposomal amphotericin B: a nationwide observational study"],"prefix":"10.1186","volume":"22","author":[{"given":"Yuki","family":"Ota","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Obata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Takazono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Tashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaro","family":"Wakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Shiozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiga","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Izumikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"2450_CR1","doi-asserted-by":"publisher","first-page":"S289","DOI":"10.1080\/13693780400025237","volume":"43","author":"M Kleinberg","year":"2005","unstructured":"Kleinberg M. Aspergillosis in the CLEAR outcomes trial: working toward a real-world clinical perspective. Med Mycol. 2005;43:S289\u201394.","journal-title":"Med Mycol"},{"key":"2450_CR2","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1086\/339202","volume":"34","author":"KA Marr","year":"2002","unstructured":"Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909\u201317.","journal-title":"Clin Infect Dis"},{"key":"2450_CR3","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s40265-016-0538-7","volume":"76","author":"NR Stone","year":"2016","unstructured":"Stone NR, Bicanic T, Salim R, Hope W. Liposomal amphotericin B (AmBisome): a review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 2016;76:485\u2013500.","journal-title":"Drugs."},{"key":"2450_CR4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.riam.2009.06.003","volume":"26","author":"R Laniado-Labor\u00edn","year":"2009","unstructured":"Laniado-Labor\u00edn R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009;26:223\u20137.","journal-title":"Rev Iberoam Micol"},{"key":"2450_CR5","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1517\/14740338.2013.827168","volume":"12","author":"AS Loo","year":"2013","unstructured":"Loo AS, Muhsin SA, Walsh TJ. Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B. Expert Opin Drug Saf. 2013;12:881\u201395.","journal-title":"Expert Opin Drug Saf"},{"key":"2450_CR6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.diagmicrobio.2017.10.018","volume":"90","author":"H Yamazaki","year":"2018","unstructured":"Yamazaki H, Kondo T, Aoki K, Yamashita K, Takaori-Kondo A. Occurrence and improvement of renal dysfunction and serum potassium abnormality during administration of liposomal amphotericin B in patients with hematological disorders: a retrospective analysis. Diagn Microbiol Infect Dis. 2018;90:123\u201331.","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2450_CR7","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1038\/ki.1992.229","volume":"41","author":"RA Zager","year":"1992","unstructured":"Zager RA, Bredl CR, Schimpf BA. Direct amphotericin B-mediated tubular toxicity: assessments of selected cytoprotective agents. Kidney Int. 1992;41:1588\u201394.","journal-title":"Kidney Int"},{"key":"2450_CR8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1681\/ASN.V4169","volume":"4","author":"SN Heyman","year":"1993","unstructured":"Heyman SN, Stillman IE, Brezis M, Epstein FH, Spokes K, Rosen S. Chronic amphotericin nephropathy: morphometric, electron microscopic, and functional studies. J Am Soc Nephrol. 1993;4:69\u201380.","journal-title":"J Am Soc Nephrol"},{"key":"2450_CR9","doi-asserted-by":"publisher","first-page":"111","DOI":"10.5049\/EBP.2007.5.2.111","volume":"5","author":"YW Kim","year":"2007","unstructured":"Kim YW. Antimicrobial-induced electrolyte and acid-base disturbances. Electrolyte Blood Press. 2007;5:111\u20135.","journal-title":"Electrolyte Blood Press"},{"key":"2450_CR10","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1172\/JCI115240","volume":"87","author":"BP Sawaya","year":"1991","unstructured":"Sawaya BP, Weihprecht H, Campbell WR, Lorenz JN, Webb RC, Briggs JP, et al. Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats. J Clin Invest. 1991;87:2097\u2013107.","journal-title":"J Clin Invest"},{"key":"2450_CR11","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/j.ekir.2018.07.014","volume":"3","author":"HB Yalamanchili","year":"2018","unstructured":"Yalamanchili HB, Calp-Inal S, Zhou XJ, Choudhury D. Hypokalemic nephropathy. Kidney Int Rep. 2018;3:1482\u20138.","journal-title":"Kidney Int Rep."},{"key":"2450_CR12","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1056\/NEJM199002083220601","volume":"322","author":"VE Torres","year":"1990","unstructured":"Torres VE, Young WF, Offord KP, Hattery RR. Association of hypokalemia, aldosteronism, and renal cysts. N Engl J Med. 1990;322:345\u201351.","journal-title":"N Engl J Med"},{"key":"2450_CR13","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1093\/ndt\/14.9.2216","volume":"14","author":"SA Menahem","year":"1999","unstructured":"Menahem SA, Perry GJ, Dowling J, Thomson NM. Hypokalaemia-induced acute renal failure. Nephrol Dial Transplant. 1999;14:2216\u20138.","journal-title":"Nephrol Dial Transplant"},{"key":"2450_CR14","doi-asserted-by":"publisher","first-page":"15033","DOI":"10.1038\/s41598-020-72135-y","volume":"10","author":"T Takazono","year":"2020","unstructured":"Takazono T, Tashiro M, Ota Y, Obata Y, Wakamura T, Miyazaki T, et al. Factor analysis of acute kidney injury in patients administered liposomal amphotericin B in a real-world clinical setting in Japan. Sci Rep. 2020;10:15033.","journal-title":"Sci Rep"},{"key":"2450_CR15","doi-asserted-by":"publisher","first-page":"487","DOI":"10.5649\/jjphcs.37.487","volume":"37","author":"T Matsuoka","year":"2011","unstructured":"Matsuoka T, Usami E, Yoshimura T, Takada H, Yasuda T. Risk factors contributing to occurrence of hypokalemia after liposomal-amphotericin B administration. J Pharm Health Care Sci. 2011;37:487\u201393.","journal-title":"J Pharm Health Care Sci"},{"key":"2450_CR16","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3892\/etm.2014.1534","volume":"7","author":"E Usami","year":"2014","unstructured":"Usami E, Kimura M, Kanematsu T, Yoshida S, Mori T, Nakashima K, et al. Evaluation of hypokalemia and potassium supplementation during administration of liposomal-amphotericin B. Exp Ther Med. 2014;7:941\u20136.","journal-title":"Exp Ther Med"},{"key":"2450_CR17","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.ekir.2017.02.008","volume":"2","author":"H Izzedine","year":"2017","unstructured":"Izzedine H, Perazella MA. Anticancer drug-induced acute kidney injury. Kidney Int Rep. 2017;2:504\u201314.","journal-title":"Kidney Int Rep"},{"key":"2450_CR18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40264-019-00873-8","volume":"43","author":"TM Patek","year":"2020","unstructured":"Patek TM, Teng C, Kennedy KE, Alvarez CA, Frei CR. Comparing acute kidney injury reports among antibiotics: a pharmacovigilance study of the FDA adverse event reporting system (FAERS). Drug Saf. 2020;43:17\u201322.","journal-title":"Drug Saf"},{"key":"2450_CR19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.jiac.2020.10.005","volume":"27","author":"M Yoshida","year":"2021","unstructured":"Yoshida M, Tamura K, Masaoka T, Nakajo E. A real-world prospective observational study on the efficacy and safety of liposomal amphotericin B in 426 patients with persistent neutropenia and fever. J Infect Chemother. 2021;27:277\u201383.","journal-title":"J Infect Chemother"},{"key":"2450_CR20","doi-asserted-by":"crossref","unstructured":"Sterns RH. Hypokalemia-induced renal dysfunction. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA: https:\/\/www.uptodate.com Accessed 16 Mar 2021.","DOI":"10.1097\/01.COT.0000805568.18162.e3"},{"key":"2450_CR21","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/j.mayocp.2016.05.018","volume":"91","author":"Y Chen","year":"2016","unstructured":"Chen Y, Chang AR, McAdams DeMarco MA, Inker LA, Matsushita K, Ballew SH, et al. Serum potassium, mortality, and kidney outcomes in the atherosclerosis risk in communities study. Mayo Clin Proc. 2016;91:1403\u201312.","journal-title":"Mayo Clin Proc"},{"key":"2450_CR22","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1515\/cclm-2016-0973","volume":"55","author":"K Kashani","year":"2017","unstructured":"Kashani K, Cheungpasitporn W, Ronco C. Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med. 2017;55:1074\u201389.","journal-title":"Clin Chem Lab Med"}],"container-title":["BMC Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-021-02450-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12882-021-02450-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-021-02450-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:44:07Z","timestamp":1672627447000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcnephrol.biomedcentral.com\/articles\/10.1186\/s12882-021-02450-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2450"],"URL":"https:\/\/doi.org\/10.1186\/s12882-021-02450-7","relation":{},"ISSN":["1471-2369"],"issn-type":[{"value":"1471-2369","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,30]]},"assertion":[{"value":"8 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki. The data herein were anonymously processed by the database provider in accordance with the Act on the Protection of Personal Information of Japan and other related regulations. For the usage of unlinkable de-identified data, ethical approval and informed consent were waived according to the Japanese Ethical Guidelines for Medical and Health Research Involving Human Subjects by the Ministry of Education, Culture, Sports, Science, and Technology and the Ministry of Health, Labour, and Welfare of Japan. The study received ethical approval from Nagasaki University School of Medicine Research Ethics Committee (approval number 18033038\u20135).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"K.I. received honorarium and research grant from Sumitomo Dainippon Pharma Co., Ltd. T.W. is a full-time employee of Sumitomo Dainippon Pharma Co., Ltd. A.T. and Y.S. are full-time employees of Deloitte Tohmatsu Consulting LLC. Deloitte Tohmatsu Consulting LLC receives consulting fees from Sumitomo Dainippon Pharma Co., Ltd. Other authors do not have any competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"240"}}