血清和尿液生物标志物在 Hypnale spp. 中毒后急性肾损伤的早期检测中的应用。
Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.
机构信息
Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
出版信息
PLoS Negl Trop Dis. 2021 Dec 6;15(12):e0010011. doi: 10.1371/journal.pntd.0010011. eCollection 2021 Dec.
BACKGROUND
Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites.
METHODS
We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming.
RESULTS
There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1-2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0-4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85-1.0) and no biomarker performed better than sCr at later time points.
CONCLUSIONS
sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.
背景
烙铁头蛇（HNV; Hypnale spp.）咬伤是斯里兰卡最常见的毒蛇咬伤。急性肾损伤（AKI）是烙铁头蛇咬伤后最严重的全身表现（1-10%）。我们旨在确定功能和损伤生物标志物在预测烙铁头蛇咬伤后早期 AKI 发展中的价值。
方法
我们对斯里兰卡两家大型三级保健医院就诊的确诊烙铁头蛇咬伤患者进行了前瞻性队列研究。前瞻性收集人口统计学、咬伤细节、临床效果、并发症和治疗数据。在咬伤后 0-4h、4-8h、8-16h 和 16-24h 以及每天直至出院时采集患者的血液和尿液样本进行凝血和肾生物标志物检测。出院后 1 个月和 3 个月时采集随访样本。在血清中测量肌酐（sCr）和胱抑素 C（sCysC），在尿液中测量肾损伤分子-1（uKIM-1）、簇蛋白（uClu）、白蛋白（uAlb）、β2-微球蛋白（uβ2M）、胱抑素 C（uCysC）、中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）、骨桥蛋白（uOPN）和三叶因子-3（uTFF-3）。确定的烙铁头蛇咬伤基于血清毒液特异性酶免疫测定。采用肾脏病：改善全球结局（KDIGO）标准对 AKI 进行分期。两名患者在 3 个月随访时患有慢性肾脏病，均有先前存在的异常 sCr，其中一名患者在烙铁头蛇咬伤后发生 AKI。
结果
共有 52 例确诊的烙铁头蛇咬伤患者；中位年龄为 48 岁（四分位间距 [IQR]：40-59 岁），29 例（56%）为男性。中位入院时间为 1.87 小时（IQR：1-2.75 小时）。12 名患者（23%）发生 AKI（AKI 1 期=7，AKI 2 期=1，AKI 3 期=4）。在发生中重度急性肾损伤的患者中，五种新型生物标志物（功能性标志物血清胱抑素 C 和损伤标志物尿 NGAL、胱抑素 C、β2-微球蛋白和簇蛋白）水平升高。在咬伤后 0-4 小时，血清胱抑素 C 预测中重度 AKI 的表现最佳（AUC-ROC 0.95；95%CI：0.85-1.0），没有任何生物标志物在后期时间点的表现优于 sCr。
结论
sCysC 似乎是一种比 sCr 更好的标志物，可用于预测烙铁头蛇咬伤后中重度 AKI。
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