Xu Katherine, Shang Ning, Levitman Abraham, Corker Alexa, Kudose Satoru, Yaeh Andrew, Neupane Uddhav, Stevens Jacob, Sampogna Rosemary, Mills Angela M, D'Agati Vivette, Mohan Sumit, Kiryluk Krzysztof, Barasch Jonathan
Department of Medicine, Columbia University, New York, New York, USA.
Department of Pathology, Columbia University, New York, New York, USA.
Kidney Int Rep. 2021 Dec;6(12):2979-2992. doi: 10.1016/j.ekir.2021.09.005. Epub 2021 Oct 8.
Loss of kidney function is a common feature of COVID-19 infection, but serum creatinine (SCr) is not a sensitive or specific marker of kidney injury. We tested whether molecular biomarkers of tubular injury measured at hospital admission were associated with acute kidney injury (AKI) in those with COVID-19 infection.
This is a prospective cohort observational study consisting of 444 consecutive patients with SARS-CoV-2 enrolled in the Columbia University emergency department (ED) at the peak of the pandemic in New York (March 2020-April 2020). Urine and blood were collected simultaneously at hospital admission (median time: day 0, interquartile range: 0-2 days), and urine biomarkers were analyzed by enzyme-linked immunosorbent assay (ELISA) and a novel dipstick. Kidney biopsies were probed for biomarker RNA and for histopathologic acute tubular injury (ATI) scores.
Admission urinary neutrophil gelatinase-associated lipocalin (uNGAL) level was associated with AKI diagnosis (267 ± 301 vs. 96 ± 139 ng/ml, < 0.0001) and staging; uNGAL levels >150 ng/ml had 80% specificity and 75% sensitivity to diagnose AKI stages 2 to 3. Admission uNGAL level quantitatively associated with prolonged AKI, dialysis, shock, prolonged hospitalization, and in-hospital death, even when admission SCr level was not elevated. The risk of dialysis increased almost 4-fold per SD of uNGAL independently of baseline SCr, comorbidities, and proteinuria (odds ratio [OR] [95% CI]: 3.59 [1.83-7.45], < 0.001). In the kidneys of those with COVID-19, NGAL mRNA expression broadened in parallel with severe histopathologic injury (ATI). Conversely, low uNGAL levels at admission ruled out stages 2 to 3 AKI (negative predictive value: 0.95, 95% CI: 0.92-0.97) and the need for dialysis (negative predictive value: 0.98, 95% CI: 0.96-0.99). Although proteinuria and urinary (u)KIM-1 were implicated in tubular injury, neither was diagnostic of AKI stages.
In the patients with COVID-19, uNGAL level was quantitatively associated with histopathologic injury (ATI), loss of kidney function (AKI), and severity of patient outcomes.
肾功能丧失是新型冠状病毒肺炎（COVID-19）感染的常见特征，但血清肌酐（SCr）并非肾损伤的敏感或特异性标志物。我们测试了入院时测量的肾小管损伤分子生物标志物是否与COVID-19感染患者的急性肾损伤（AKI）相关。
这是一项前瞻性队列观察性研究，纳入了纽约疫情高峰期（2020年3月至2020年4月）在哥伦比亚大学急诊科（ED）连续收治的444例严重急性呼吸综合征冠状病毒2（SARS-CoV-2）患者。入院时（中位时间：第0天，四分位间距：0 - 2天）同时采集尿液和血液，通过酶联免疫吸附测定（ELISA）和一种新型试纸条分析尿液生物标志物。对肾活检组织进行生物标志物RNA检测和组织病理学急性肾小管损伤（ATI）评分。
入院时尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）水平与AKI诊断（267±301 vs. 96±139 ng/ml，<0.0001）及分期相关；uNGAL水平>150 ng/ml对诊断2至3期AKI的特异性为80%，敏感性为75%。入院时uNGAL水平与AKI持续时间延长、透析、休克、住院时间延长及院内死亡在数量上相关，即使入院时SCr水平未升高。uNGAL每增加1个标准差，透析风险增加近4倍，独立于基线SCr、合并症和蛋白尿（比值比[OR][95%可信区间]：3.59[1.83 - 7.45]，<0.001）。在COVID-19患者的肾脏中，NGAL mRNA表达与严重组织病理学损伤（ATI）平行增加。相反，入院时uNGAL水平低可排除2至3期AKI（阴性预测值：0.95，95%可信区间：0.92 - 0.97）及透析需求（阴性预测值：0.98，95%可信区间：0.96 - 0.�9）。虽然蛋白尿和尿（u）KIM-1与肾小管损伤有关，但两者均不能诊断AKI分期。
在COVID-19患者中，uNGAL水平与组织病理学损伤（ATI）、肾功能丧失（AKI）及患者预后严重程度在数量上相关。
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