住院患者使用两性霉素B脱氧胆酸盐后发生急性肾损伤的危险因素分析与预测模型构建

Risk Factors Analysis and Predictive Model Construction for Acute Kidney Injury Following Amphotericin B Deoxycholate Use in Hospitalized Patients

  • 摘要:
    目的 探讨两性霉素B脱氧胆酸盐使用后发生急性肾损伤(acute kidney injury,AKI)的危险因素及构建预测模型以指导临床监测与干预。
    方法 采用回顾性分析,纳入2014年1月至2024年9月使用两性霉素B脱氧胆酸盐的住院患者,分为训练集和验证集。提取患者一般资料、实验室检查结果和药品医嘱,根据用药期间及停药后7 d内是否发生AKI,将患者分为AKI组与非AKI组。通过单因素分析筛选潜在危险因素,采用多因素Logistic回归构建预测模型,并通过受试者操作特征曲线下面积和Hosmer-Lemeshow检验评估模型性能。
    结果 训练集共纳入473例患者,其中男性255例(53.91%)、女性218例(46.09%),中位年龄为52(35,62)岁,AKI组191例(40.38%)、非AKI组282例(59.62%);验证集共纳入114例患者,其中男性80例(70.18%)、女性34例(29.82%),中位年龄为43.5(31.0,58.5)岁,AKI组42例(36.84%)、非AKI组72例(63.16%)。单因素分析显示两组患者一般资料(年龄、进入重症监护室治疗、死亡、住院时间)、实验室检查结果(血肌酐高于正常值、尿素高于正常值、中性粒细胞百分比低于正常值、中性粒细胞百分比高于正常值、淋巴细胞百分比低于正常值、血钠高于正常值)、合并用药(非甾体抗炎药、抗真菌药物、神经系统药物、肾上腺素类药物、碳酸氢钠片/注射液、苯海拉明/异丙嗪注射液、非甾体抗炎药+苯海拉明/异丙嗪、非甾体抗炎药+糖皮质激素、苯海拉明/异丙嗪+糖皮质激素、非甾体抗炎药+苯海拉明/异丙嗪+糖皮质激素)、合并症(糖尿病、肾病、心功能不全)共23个因素差异具有统计学意义(P均<0.05)。多因素分析显示,进入重症监护室治疗(OR=2.128,95% CI:1.415~3.201)、入院血肌酐高于正常值(OR=1.920,95% CI:1.235~2.985)、合并心功能不全(OR=3.394,95% CI:1.369~8.417)为危险因素,而预防性使用苯海拉明/异丙嗪注射液(OR=0.182,95% CI:0.083~0.399)或碳酸氢钠片/注射液(OR=0.512,95% CI:0.339~0.773)为保护因素。预测模型方程式为:logit(P)=lnP/(1-P)=-0.479+0.755Xs1+0.652X2+1.222X3-1.702X4-0.67X5(X1为进入重症监护室治疗,X2为入院血肌酐高于正常值,X3为合并心功能不全,X4为合并使用苯海拉明/异丙嗪注射液,X5为合并使用碳酸氢钠片/注射液,X根据是否满足条件取值“1”或者“0”)。该模型在训练集和验证集的AUC分别为0.735(95% CI:0.691~0.780)和0.699(95% CI:0.604~0.795),Hosmer-Lemeshow检验显示,χ2值为4.048,P=0.774,提示模型校准度良好。
    结论 进入重症监护室治疗、入院血肌酐升高以及合并心功能不全是AKI发生的潜在危险因素,而预防性使用苯海拉明/异丙嗪或碳酸氢钠则表现出保护性关联,所构建的预测模型具有良好区分度和校准度,可为临床早期识别高危患者以及治疗方案的及时调整提供参考。

     

    Abstract:
    Objective To investigate the risk factors for acute kidney injury (AKI) following the use of amphotericin B deoxycholate and to develop a predictive model to guide clinical monitoring and intervention.
    Methods A retrospective analysis was conducted on hospitalized patients who received amphotericin B deoxycholate between January 2014 and September 2024. Patients were divided into a training set and a validation set. Demographic data, laboratory findings, and medication orders were collected. Based on the occurrence of AKI during treatment and within 7 days after discontinuation, patients were classified into an AKI group and a non-AKI group. Univariate analysis was used to screen for potential risk factors, multivariate logistic regression was employed to construct a predictive model, and model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow test.
    Results The training set included 473 patients, comprising 255 males (53.91%) and 218 females (46.09%), with a median age of 52(35, 62) years. The AKI group consisted of 191 cases (40.38%), and the non-AKI group consisted of 282 cases (59.62%). The validation set included 114 patients, comprising 80 males (70.18%) and 34 females (29.82%), with a median age of 43.5 (31.0, 58.5) years. The AKI group consisted of 42 cases (36.84%), and the non-AKI group consisted of 72 cases (63.16%). Univariate analysis revealed statistically significant differences between the two groups in 23 factors (all P < 0.05), including demographic data (age, admission to intensive care unit (ICU), death, length of hospital stay), laboratory findings (serum creatinine above normal, urea above normal, neutrophil percentage below normal, neutrophil percentage above normal, lymphocyte percentage below normal, serum sodium above normal), concomitant medications (nonsteroidal anti-inflammatory drugs (NSAIDs), antifungal agents, neurological drugs, adrenergic drugs, sodium bicarbonate tablets/injection, diphenhydramine/promethazine injection, NSAIDs+ diphenhydramine/promethazine, NSAIDs+ corticosteroids, diphenhydramine/promethazine+corticosteroids, NSAIDs+ diphenhydramine/prome-thazine+corticosteroids), and comorbidities (diabetes mellitus, kidney disease, cardiac insufficiency)(all P < 0.05). Multivariate analysis identified admission to the ICU (OR=2.128, 95% CI: 1.415-3.201), elevated serum creatinine at admission (OR=1.920, 95% CI: 1.235-2.985), and comorbid cardiac insufficiency (OR=3.394, 95% CI: 1.369-8.417) as risk factors, while prophylactic use of diphenhydramine/promethazine injection (OR=0.182, 95% CI: 0.083-0.399) or sodium bicarbonate tablets/injection (OR=0.512, 95% CI: 0.339-0.773) were protective factors.The prediction model equation is as follows. logit(P)=lnP/(1-P)= -0.479+0.755X1+0.652X2+1.222X3-1.702X4-0.67X5 (X1 admitted to the intensive care unit, X2 admitted to the hospital with higher serum creatinine than the normal value, X3 complicated with cardiac insufficiency, X4 combined with diphenhydramine/promethazine injection, X5 was combined with sodium bicarbonate tablets/injection, X was taken as "1" or "0" according to whether the conditions were met). The AUC of the model was 0.735 (95% CI: 0.691-0.780) in the training set and 0.699 (95% CI: 0.604-0.795) in the validation set. The Hosmer-Lemeshow test yielded a χ2 value of 4.048 (P=0.774), indicating good model calibration.
    Conclusions Admission to the ICU, elevated serum creatinine at admission, and comorbid cardiac insufficiency as potential risk factors for AKI, while prophylactic use of diphenhydramine/promethazine or sodium bicarbonate showed a protective association. A predictive model with good discrimina-tion and calibration was developed, which may provide a basis for early identification of high-risk patients and timely adjustment of treatment strategies in clinical practice.

     

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