基于文献病例的万古霉素致急性肾损伤严重程度和预后影响因素分析

Analysis of factors influencing the severity and prognosis of vancomycin-induced acute kidney injury based on literature cases

目的探讨万古霉素相关急性肾损伤(AKI)严重程度和预后的影响因素。方法检索国内外相关数据库(截至2020年6月),收集万古霉素相关AKI的病例报告类文献,记录患者的一般情况、基础疾病、感染菌种、万古霉素应用情况、基线血清肌酐(Scr)、基线估算肾小球滤过率(eGFR)、AKI发生时间、Scr升高率、eGFR下降率、AKI处理及预后等信息进行描述性分析,采用稳健回归分析法分析患者Scr升高程度和eGFR下降程度的影响因素,通过比较Scr水平基本恢复与好转患者的主要临床特征,分析万古霉素相关AKI预后的影响因素。结果纳入分析的文献共81篇,包括109例患者,男性65例,女性44例;年龄1~84岁,中位年龄49岁,≤15岁儿童20例;61例(56.0%)有慢性基础疾病。万古霉素中位日剂量89例成人患者为2.00(0.75,6.00)g,20例患儿为40.0(10.3,240.0)mg/kg。开始应用万古霉素至发生AKI的中位时间为7(1,135)d,其中80例(73.4%)发生在用药14 d以内;75例(68.8%)合并应用了有潜在肾毒性的药物。发生AKI后Scr的中位峰值为408(53,1000)μmol/L,中位eGFR为44.3(4.2,280.7)ml/(min·1.73 m^(2))。57例患者有稳态血药谷浓度的描述,发生AKI前或发生AKI时万古霉素中位血药谷浓度为46.2(11.8,284.0)mg/L。50例患者Scr水平基本恢复,51例好转,3例未恢复需持续肾替代治疗,4例死亡,1例失访。稳健回归分析结果显示,万古霉素血药谷浓度及合并应用肾毒性药物种数与AKI发生后Scr升高和eGFR下降程度明显相关(均P<0.05)。Scr水平基本恢复的患者年龄和Scr峰值明显低于好转的患者(均P<0.001),而eGFR最低值明显高于好转的患者(P=0.036)。结论万古霉素血药谷浓度越高,合并使用肾毒性药物种数越多,Scr升高及eGFR下降幅度越大;患者年龄越大,AKI发生后Scr峰值越高,eGFR越低,肾功能恢复越差。

Objective Toexplore the factors influencing the severity and prognosis of vancomycinassociated acute kidney injury(AKI).Methods Case reports on vancomycin-associated AKI were collected by searching the relevant databases home and abroad up to June 2020.Patients′relevant information such as general condition,underlying diseases,infecting species,treatment of vancomycin,baseline serum creatinine(Scr),baseline estimated glomerular filtration rate(eGFR),time from medication to onset of AKI,Scr elevation rate,eGFR decline rate,management of AKI,and outcomes were recorded and descriptively analyzed.The influence factors of the rates of Scr elevation and eGFR decline in patients were analyzed using robust regression method and the influence factors of the prognosis of vancomycin-associated AKI were analyzed by comparing the main clinical features of patients with basic recovery and improvement of Scr level.Results A total of 81 reports involving 109 patients were enrolled in the analysis,including 65 males and 44 females,aged from 1 to 84 years with a median age of 49 years,of which 20 were≤15 years old and 61(56.0%)suffered from underlying chronic diseases.The median daily dose of vancomycin was 2.00(0.75,6.00)g in 89 adult patients and 40.0(10.3,240.0)mg/kg in 20 pediatric patients.The median time from medication to onset of AKI was 7(1,135)days,and 80(73.4%)occurred within 14 days after first medication.Seventy-five patients(68.8%)had concomitant use of drugs with potential nephrotoxicity.The median value of peak Scr was 408(53,1000)μmol/L,and the median eGFR was 44.3(4.2,280.7)ml/(min·1.73 m^(2))after developing AKI.Steady-state trough concentration of vancomycin was recorded in 57 patients,which was 46.2(11.8,284.0)mg/L before or at onset of AKI.Except 4 patients died and 1 patient was lost to follow-up,the Scr level basically recovered in 50 patients,were improved in 51 patients,and did not recover in 3 patients,which required continuous renal replacement therapy.Robust regression analysis showed that the trough concentration of vancomycin and the number of concomitant nephrotoxic drugs were significantly correlated with the rates of Scr elevation and eGFR decline after AKI(all P<0.05).The age and peak Scr in patients with basic recovery of renal function were significantly lower than those in patients with improved renal function(all P<0.001),while the lowest eGFR value was significantly higher(P=0.036).Conclusions Patients with higher trough concentration of vancomycin and more nephrotoxic drugs would have greater elevation of Scr and the decline of eGFR.Older age,higher Scr peak value,and lower eGFR was associated with worse recovery of the renal function.