Analysis of adverse drug reactions and renally inappropriate medication in patients with chronic kidney disease
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摘要:
背景 慢性肾病(chronic kidney disease，CKD)患者由于自身疾病和不适当用药等原因更易发生药品不良反应(adverse drug reaction，ADR)，减少CKD患者不适当用药，预防ADR的发生具有重要的临床意义。 目的 分析CKD患者ADR的发生特点和肾不适当用药(renally inappropriate medication，RIM)的发生率，为CKD患者临床合理用药提供参考。 方法 分析2009 - 2021年解放军总医院第一医学中心肾病科上报的ADR报告，统计患者基本情况、CKD分期、药物种类、ADR累及系统和器官等，并根据药品说明书及相关指南和专家共识评估ADR报告中RIM的发生情况。 结果 本研究共纳入629例CKD患者的ADR报告(严重ADR报告93例)，男女比例为1.18∶1，以40 ~ 59岁ADR例数最多。引发ADR频次较多的为心血管系统药物、抗感染药物、电解质/酸碱平衡/营养药物。累及系统-器官共849例，主要涉及胃肠道系统损害156例(18.37%)，皮肤及皮肤附件损害139例(16.37%)，全身性损害107例(12.60%)。ADR报告中共发现61例(9.69%)RIM，涉及严重ADR报告19例(31.15%)。RIM发生频次最高的药品和RIM涉及严重ADR最多的药品均为左氧氟沙星。 结论 CKD患者ADR涉及药物品种较多，累及多个系统和器官，部分ADR与RIM有关，应加强CKD患者用药监测，减少肾不适当用药，尤其关注抗感染药物和心血管系统药物，并谨慎使用肾毒性药物。 Abstract:Background Patients with chronic kidney disease (CKD) are more prone to have adverse drug reaction (ADR) due to their own diseases and inappropriate medication. It is of great clinical significance to reduce inappropriate medication and to prevent ADR for CKD. Objective To analyze ADRs occurred in CKD patients and the renally inappropriate medication (RIM) for providing reference to rational drug use in patients with CKD. Methods ADRs reported by the nephrology department in our hospital from 2009 to 2021 were analyzed, including the basic information of patients, CKD stages, drug types, and the involved system/organs. The occurrence of RIMs in ADR reports were evaluated according to the drug instructions, relevant guidelines and expert consensus. Results A total of 629 ADRs were included, including 93 severe ADRs, with a male to female ratio of 1.18:1, and they occurred most frequently in CKD with age of 40-59 years. The top three categories of ADRs were cardiovascular drugs, anti-infective drugs, electrolyte, acid-base balance and nutritional drugs. Many systemic/organs (849 cases) were involved, the top three were gastrointestinal disorders (156 cases, 18.37%), skin and appendages disorder (139 cases, 16.37%), body as a whole-general disorders (107 cases, 12.60%). A total of 61 (9.69%) RIMs were found in ADR reports, including 19 (31.15%) serious ADRs. Levofloxacin was the most common drug both of RIM and serious ADR in RIM. Conclusion There are multiple drugs and systems/organs involved in ADR of CKD patients, and part of them are related to RIM. Therefore, we should strengthen medication monitoring in CKD patients and reduce RIMs, especially when we use the anti-infective, cardiovascular, and nephrotoxic drugs. -
表 1 629例ADR患者基本情况
Table 1. Basic information of the 629 patients with ADR
因素 ADR报告/(例，%) 严重ADR
发生率/%P值 严重(93例) 总(629例) 性别 0.869 男 51(54.84) 340(54.05) 15.00 女 42(45.16) 289(45.95) 14.53 年龄 0.243 0 ~ 19岁 2(2.15) 22(3.50) 9.09 20 ~ 39岁 18(19.35) 168(26.71) 10.71 40 ~ 59岁 44(47.31) 253(40.22) 17.39 60 ~ 80岁 25(26.88) 170(27.03) 14.71 80 ~ 99岁 4(4.30) 16(2.54) 25.00 CKD分期 0.008 G1 ~ 3 37(39.78) 330(52.46) 11.21 G4 ~ 5 56(60.22) 299(47.54) 18.73 
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表 2 629例ADR报告中涉及的药物类别(例)
Table 2. Types of drugs involved in 629 ADR reports (n)
药物分类 严重ADR 总ADR 代谢及内分泌系统用药 10 48 电解质、酸碱平衡及营养药 6 62 呼吸系统用药 0 6 精神障碍用药 1 5 抗感染药 27 107 免疫系统用药 12 61 神经系统用药 2 52 生物制品 0 10 生殖系统用药 2 6 消化系统用药 3 19 心血管系统用药 12 125 血液系统用药 6 50 镇痛药 1 3 中药成方 6 30 肿瘤用药 3 23 酶类及其他生化药 2 19 其他药物 0 3 总计 93 629
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表 3 25例尿路损害报告中涉及的药物品种和表现
Table 3. Drug types and manifestations in 25 cases of urinary tract injury
序号 药品名称 药品类别 表现(频次) 1 苯溴马隆 代谢及内分泌
系统用药急性肾功能衰竭(1) 2 左卡尼汀 电解质、酸碱平
衡及营养药血肌酐升高(1) 3 阿米替林 精神障碍用药 排尿困难(1) 4 左氧氟沙星 抗感染药 血肌酐升高(1) 5 伏立康唑 抗感染药 血肌酐升高(1) 6 哌拉西林钠
他唑巴坦钠抗感染药 血肌酐升高(1) 7 利福喷丁 抗感染药 血肌酐升高(1) 8 阿昔洛韦 抗感染药 血肌酐升高(1) 9 阿莫西林克
拉维酸钾抗感染药 血肌酐升高伴血尿(1) 10 环孢素 免疫系统用药 血肌酐升高(1) 11 他克莫司 免疫系统用药 血肌酐升高(3) 12 马来酸桂哌齐特 心血管系统用药 血肌酐升高(1) 13 奥美沙坦酯片 心血管系统用药 血肌酐升高(1) 14 磷酸肌酸钠 心血管系统用药 血肌酐升高(1) 15 氯沙坦钾 心血管系统用药 血肌酐升高(3)、无尿症(1) 16 前列地尔 心血管系统用药 血尿(1) 17 那屈肝素钙 血液系统用药 血尿(1) 18 酚磺乙胺 血液系统用药 排尿困难(1) 19 对乙酰氨基酚 镇痛药 血肌酐升高(1) 20 环磷酰胺 肿瘤用药 血尿加重(1)
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表 4 629例ADR报告中涉及的RIM情况(例，%)
Table 4. RIM involved in 629 ADR reports (n, %)
药物品种 RIM频次 严重ADR 类别 抗感染药 33(54.10) 12(63.16) 左氧氟沙星(16)、复方磺胺甲噁唑(3)、美罗培南(3)、哌拉西林钠他唑巴坦钠(3)、头孢美唑钠(2)、
头孢哌酮钠舒巴坦钠(2)、阿莫西林克拉维酸钾(1)、恩替卡韦(1)、伏立康唑(1)、亚胺培南西司他丁钠(1)神经系统用药 2(3.28) 1(5.26) 加巴喷丁(1)、盐酸普拉克索(1) 生殖系统用药 3(4.92) 2(10.53) 垂体后叶素(3) 心血管系统用药 19(31.15) 3(15.79) 阿昔莫司(14)、瑞舒伐他汀钙(2)、苯扎贝特(1)、磷酸肌酸钠(1)、氯沙坦钾(1) 血液系统用药 1(1.64) - 那屈肝素钙(1) 镇痛药 2(3.28) 1(5.26) 对乙酰氨基酚(1)、氟比洛芬酯(1) 肿瘤用药 1(1.64) - 唑来膦酸(1) 总计 61 19
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表 5 肾不适当用药涉及的19例严重不良反应分布情况
Table 5. Distribution of RIM in 19 cases of severe adverse reactions
药品名称 ADR表现(频次) RIMs 左氧氟沙星 癫痫发作(2)、血肌酐升高(1)、意识丧失伴抽搐(1)、肝功能异常(1)、过敏性休克(1) CKD5期，未调整药物剂量 垂体后叶素 左心衰竭(1)、血压升高(1) CKD5期，禁用 对乙酰氨基酚 肝肾功能异常(1) CKD5期，禁用 头孢美唑钠 过敏性休克(1) CKD5期，未调整药物剂量 氯沙坦钾 无尿症(1) CKD5期，慎用 阿莫西林克拉维酸钾 肾功能异常伴血尿(1) CKD5期，未调整药物剂量 复方磺胺甲噁唑 血小板减少(1) CKD5期，不建议使用 哌拉西林钠他唑巴坦钠 血肌酐升高(1) CKD3期，未调整药物剂量 头孢哌酮钠舒巴坦钠 凝血障碍(1) CKD5期，未调整药物剂量 瑞舒伐他汀钙 肝功能异常(1) CKD4期，禁用 伏立康唑 血肌酐升高(1) CKD5期，慎用注射剂 加巴喷丁 低血压伴嗜睡(1) CKD5期，未调整药物剂量 苯扎贝特 肝损伤伴横纹肌溶解(1) CKD5期，禁用
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[1] Maříková M,Očovská Z,Nerad V,et al. Hospital admissions to geriatric ward related to adverse drug events:a cross-sectional study from the Czech Republic[J]. Int J Clin Pharm,2021,43(5): 1218-1226. doi: 10.1007/s11096-021-01237-y [2] Li R,Curtis K,Zaidi STR,et al. Prevalence,characteristics,and reporting of adverse drug reactions in an Australian hospital:a retrospective review of hospital admissions due to adverse drug reactions[J]. Expert Opin Drug Saf,2021,20(10): 1267-1274. doi: 10.1080/14740338.2021.1938539 [3] Mejía G,Saiz-Rodríguez M,Gómez de Olea B,et al. Urgent hospital admissions caused by adverse drug reactions and medication errors-A population-based study in Spain[J]. Front Pharmacol,2020,11: 734. doi: 10.3389/fphar.2020.00734 [4] Danial M,Hassali MA,Ong LM,et al. Survivability of hospitalized chronic kidney disease (CKD) patients with moderate to severe estimated glomerular filtration rate (eGFR) after experiencing adverse drug reactions (ADRs) in a public healthcare center:a retrospective 3 year study[J]. BMC Pharmacol Toxicol,2018,19(1): 52. doi: 10.1186/s40360-018-0243-0 [5] Kimura H,Tanaka K,Saito H,et al. Association of polypharmacy with kidney disease progression in adults with CKD[J]. Clin J Am Soc Nephrol,2021,16(12): 1797-1804. doi: 10.2215/CJN.03940321 [6] Deskur-Śmielecka E,Chudek J,Neumann-Podczaska A,et al. Use of renal risk drugs in a nation-wide Polish older adult population:an analysis of PolSenior database[J]. BMC Geriatr,2019,19(1): 70. doi: 10.1186/s12877-019-1075-5 [7] Kidney Disease:Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease[J]. Kidney Int,2020,98(4S): S1-S115. [8] 陈新谦, 金有豫, 汤光. 陈新谦新编药物学［M］. 18版. 北京: 人民卫生出版社, 2018. [9] 国家药品不良反应监测中心. 药品不良反应术语使用指南［M］. 北京: 国家药品不良反应监测中心, 2016. [10] 陈丽丹. 应用氟喹诺酮类药物治疗的不良反应发生情况探讨[J]. 中国实用医药,2021,16(25): 186-188. [11] Jin HY,Wang TS,Falcione BA,et al. Trough concentration of voriconazole and its relationship with efficacy and safety:a systematic review and meta-analysis[J]. J Antimicrob Chemother,2016,71(7): 1772-1785. doi: 10.1093/jac/dkw045 [12] Tsui L, Ye P, Xu S, et al. Adverse drug reactions of statin therapy in China from 1989 to 2019: a national database analysis［J/OL］. https://doi.org/10.1136/ejhpharm-2022-003333. [13] Perazella MA. Pharmacology behind common drug nephrotoxicities[J]. Clin J Am Soc Nephrol,2018,13(12): 1897-1908. doi: 10.2215/CJN.00150118 [14] Derungs A. Drug-induced acute kidney injury[J]. Ther Umsch,2015,72(11/12): 717-727. doi: 10.1024/0040-5930/a000742 [15] Cui Y,Yang Y,Lei WH,et al. The clinicopathological features of drug-induced acute kidney injury-a single-center retrospective analysis[J]. Ann Transl Med,2021,9(5): 400. doi: 10.21037/atm-20-3826 [16] 李超,李晨,单青,等. 老年慢性肾脏病患者肾脏不适当用药评价[J]. 中国医院药学杂志,2022,42(12): 1267-1270. [17] 陈婷婷. 左氧氟沙星导致的不良反应及危险因素分析[J]. 中国民康医学,2021,33(22): 159-160. doi: 10.3969/j.issn.1672-0369.2021.22.058 [18] Oreagba IA,Oshikoya KA,Ogar C,et al. Adverse reactions to fluoroquinolones in the Nigerian population:an audit of reports submitted to the National Pharmacovigilance Centre from 2004 to 2016[J]. Pharmacol Res Perspect,2017,5(2): e00297. doi: 10.1002/prp2.297 [19] 彭佳,陈志宏,刘丽华,等. 2015—2020年长沙市2478例左氧氟沙星致药品不良反应的报告分析[J]. 中国医院用药评价与分析,2021,21(10): 1269-1272. -
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