Analysis of Nephrotoxicity and Hypokalemia during the Use of Liposomal Amphotericin B in Children with Febrile Neutropenia

Z. Özdemir, Meral Barış, Y. D. Kar, Ersin Töret, Hülya Özen, Özcan Bör
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Abstract

Purpose: Invasive fungal infections are an important cause of morbidity and mortality in children with febrile neutropenia. Although liposomal amphotericin B (L-AMB) is used safely due to its broad antifungal activity, it causes important side effects such as nephrotoxicity and hypokalemia. Methods: Medical records of 45 children with hematological malignancies who were given empirical L-AMB for febrile neutropenia between November 2011 and December 2019 were reviewed retrospectively. The estimated glomerular filtration rate (eGFR), serum creatinine and potassium levels were compared before and after 7th day of L-AMB treatment. Results: 62 febrile neutropenic attacks of 45 children were evaluated. The median age of the patients was 8.25 (3.5-13) years, and the number of attacks per patient was between 1-5. The median duration of treatment with L-AMB was 14 (range 9-21) days. Nephrotoxicity developed in 16 attacks (26%), and hypokalemia developed in 26 attacks (42%). In those who developed nephrotoxicity, eGFR was lower and creatinine level was higher after 7th day of L-AMB treatment, compared to their values before treatment. The frequency of hypokalemia was low in attacks where nephrotoxicity has been developed. High eGFR, and low creatinine level were risk factors with borderline significance from the point of development of nephrotoxicity. Conclusion: Potassium level should be carefully monitored and appropriate replacement therapy should be administered in febrile neutropenic children with hematological malignancy receiving L-AMB therapy. Parenteral hydration before L-AMB administration does not prevent nephrotoxicity, however it positively affects the frequency of nephrotoxicity.
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两性霉素B脂质体治疗发热性中性粒细胞减少症的肾毒性和低钾血症分析
目的:侵袭性真菌感染是发热性中性粒细胞减少症患儿发病和死亡的重要原因。尽管脂质体两性霉素B (L-AMB)由于其广泛的抗真菌活性而被安全使用,但它会引起严重的副作用,如肾毒性和低钾血症。方法:回顾性分析2011年11月至2019年12月45例血液系统恶性肿瘤患儿经验性L-AMB治疗发热性中性粒细胞减少症的病历。比较L-AMB治疗第7天前后的肾小球滤过率(eGFR)、血清肌酐和钾水平。结果:对45例患儿62例发热性中性粒细胞减少症进行了评价。患者年龄中位数为8.25(3.5 ~ 13)岁,发作次数1 ~ 5次/例。L-AMB治疗的中位持续时间为14天(范围9-21天)。16次发作发生肾毒性(26%),26次发作发生低钾血症(42%)。在发生肾毒性的患者中,与治疗前相比,L-AMB治疗第7天后eGFR较低,肌酐水平较高。在已发生肾毒性的发作中,低钾血症的发生率较低。高eGFR和低肌酐水平从肾毒性的发展角度来看是具有临界意义的危险因素。结论:血液学恶性肿瘤发热性中性粒细胞减少患儿接受L-AMB治疗时应密切监测钾水平,并给予适当的替代治疗。L-AMB给药前的静脉补水不能预防肾毒性,但可以积极影响肾毒性的发生频率。
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