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应用肾损伤生物标志物对圆斑蝰蛇(Daboia russelii)咬伤后急性肾损伤的早期识别。

Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers.

机构信息

South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.

TACT, Department of Pharmacology, Sydney Medical School, University of Sydney, Sydney, Australia.

出版信息

PLoS Negl Trop Dis. 2019 Jul 1;13(7):e0007486. doi: 10.1371/journal.pntd.0007486. eCollection 2019 Jul.

Abstract

BACKGROUND

Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites.

METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7).

CONCLUSIONS/SIGNIFICANCE: AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.

摘要

背景

急性肾损伤(AKI)是蛇咬伤的主要并发症,但早期诊断仍存在问题。我们旨在研究眼镜蛇(Daboia russelii)咬伤后 AKI 中新型肾脏生物标志物的时间过程。

方法/主要发现:我们招募了一组明确的眼镜蛇咬伤患者,并在入院时(<4 小时后咬伤)、4-8 小时、8-16 小时、16-24 小时、1 个月和 3 个月收集了一系列血样和尿样。AKI 分期(1-3 期)采用急性肾损伤网络标准定义。AKI 分期(1-3 期)由急性肾损伤网络(AKIN)标准定义。共有 65 例眼镜蛇咬伤患者,其中 49 例发生 AKI:24 例 AKIN 分期 1 期,13 例分期 2 期,12 例分期 3 期。毒液浓度与 AKI 分期(p=0.007)和 AKI 分期与 6 个峰值生物标志物浓度之间存在显著相关性。虽然大多数生物标志物浓度在 8 小时内升高,但没有生物标志物在 4 小时内对 AKI 进行良好诊断。在 4-8 小时内,三种生物标志物优于血清肌酐(sCr)预测 AKI(2/3 期):血清胱抑素 C(sCysC)的曲线下面积(AUC-ROC)为 0.78(95%CI:0.64-0.93),尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)为 0.74(95%CI:0.59-0.87),尿簇蛋白(uClu)为 0.81(95%CI:0.69-0.93)。在 8 小时后,没有生物标志物优于 sCr。其他 6 种尿液生物标志物,如尿液白蛋白、尿液β2-微球蛋白、尿液肾损伤分子 1、尿液胱抑素 C、尿液三叶因子 3 和尿液骨桥蛋白,其水平升高有限,并且/或者对 AKI 2/3 期的预测作用有限(AUC-ROC<0.7)。

结论/意义:眼镜蛇咬伤后 AKI 很常见,有时很严重。三种生物标志物 uClu、uNGAL 和 sCysC,似乎比 sCr 更早出现异常,可能有助于早期识别蛇毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec0f/6625728/8950a07962fd/pntd.0007486.g001.jpg

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