Sampaio de Souza Garms Durval, Cardoso Eid Karina Zanchetta, Burdmann Emmanuel A, Marçal Lia Junqueira, Antonângelo Leila, Dos Santos Adriano, Ponce Daniela
Department of Internal Medicine, University of São Paulo State, São Paulo, Brazil.
LIM 12, Nephrology Discipline of University of São Paulo, São Paulo, Brazil.
Front Pharmacol. 2021 Sep 23;12:705636. doi: 10.3389/fphar.2021.705636. eCollection 2021.
The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown. The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin. A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5. Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16-38.22, = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096-1.290, = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11-22.02, = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98-1.06, = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10-1.62, = 0.02; OR 1.19, CI 1.09-1.39, = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge. AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.
与万古霉素相关的急性肾损伤（AKI）的发生率各不相同，一些与治疗及患者相关的风险因素可能解释其肾毒性。尿生物标志物在与万古霉素相关的AKI中的作用尚不清楚。本研究的目的是评估尿白细胞介素-18（IL-18）、肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、金属蛋白酶组织抑制因子-2（TIMP-2）和胰岛素样生长因子结合蛋白7（IGFBP7）作为与万古霉素相关的AKI的诊断和预后预测指标的作用。对2019年7月至2020年5月期间在一所公立大学医院病房接受万古霉素治疗的患者进行了一项前瞻性队列研究。我们排除了在开始使用万古霉素前就患有AKI、血流动力学不稳定、无法收集尿液以及慢性肾脏病5期的患者。共纳入94例患者，AKI的患病率为24.5%，总体死亡率为8.7%。AKI发生在首次使用万古霉素后11±2天。最常见的肾脏病改善全球预后（KDIGO）分期为1期（61%）。因性别、住院时间、剂量和使用万古霉素的时间不同，发生和未发生AKI的患者之间没有差异。逻辑回归分析确定年龄（比值比[OR]6.6，95%置信区间[CI]1.16 - 38.22，P = 0.03）、96至144小时的血浆万古霉素浓度（OR 1.18，CI 1.04 - 1.40，P = 0.04）以及96至144小时的尿NGAL水平（OR 1.123，CI 1.096 - 1.290，P = 0.03）为AKI的预测指标。使用万古霉素的时间（OR 4.61，CI 1.11 - 22.02，P = 0.03）、192至240小时较高的血浆万古霉素浓度（OR 1.02，CI 0.98 - 1.06，P = 0.26）以及144至192小时较高的细胞周期阻滞尿生物标志物TIMP-2乘以IGFBP-7（分别为OR 1.33，CI 1.10 - 1.62，P = 0.02；OR 1.19，CI 1.09 - 1.39，P = 0.04）被确定为出院时肾功能未恢复的预后因素。在病房住院的患者中，与万古霉素相关的AKI很常见。年龄、血浆万古霉素浓度以及96至144小时的NGAL被确定为与使用万古霉素相关的AKI的预测指标。血浆万古霉素浓度和尿NGAL是未来5天内AKI诊断的预测指标。细胞周期阻滞的尿生物标志物TIMP-2和IGFBP-7以及万古霉素的使用时间与出院时肾功能未恢复有关。
