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急性高胆红素血症导致早期亚临床肾脏损伤:胆源性肾病中肾小管生物标志物的评估。

Acute hyperbilirubinemia determines an early subclinical renal damage: Evaluation of tubular biomarkers in cholemic nephropathy.

机构信息

Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy.

出版信息

Liver Int. 2024 Sep;44(9):2341-2350. doi: 10.1111/liv.16005. Epub 2024 Jun 4.

Abstract

BACKGROUND AND AIMS

Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys).

METHODS

This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice.

RESULTS

Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes.

CONCLUSIONS

This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).

摘要

背景和目的

胆源性肾病是一种发生于黄疸患者的急性肾损伤病因。本研究旨在评估无临床常用参数(血清肌酐或尿素)改变且肾脏形态正常的轻度急性高胆红素血症患者的早期肾功能损害。我们研究了尿中性粒细胞明胶酶相关脂质运载蛋白(u-NGAL)、尿β2-微球蛋白(u-B2M)、尿骨桥蛋白(u-OPN)、尿三叶因子 3(u-TFF3)和尿胱抑素 C(u-Cys)等肾小管损伤的尿生物标志物。

方法

这是一项病例对照研究,调查了轻度急性高胆红素血症患者的这些肾小管损伤尿生物标志物:u-NGAL、u-B2M、u-OPN、u-TFF3 和 u-Cys。本研究纳入了 74 例患者:36 例黄疸患者和 38 例无黄疸患者。

结果

黄疸患者(总胆红素 12.4±7.3mg/dL)的 u-NGAL、u-B2M、u-OPN、u-TFF3 和 u-Cys 均高于对照组。在包括以下独立变量的逻辑回归分析后:年龄、估计肾小球滤过率(eGFR)、血红蛋白、糖尿病、高血压和黄疸,我们观察到黄疸患者 u-NGAL 值升高的风险更高(OR=3.8,95%CI 1.07-13.5,p=0.03)和 u-B2M(OR=9.4,95%CI 2.3-38.9,p=0.0018)。此外,尿生物标志物与血清胆汁淤积指标直接相关。

结论

本研究表明,与对照组相比,轻度高胆红素血症患者的尿肾小管损伤生物标志物(u-NGAL、u-B2M、u-OPN、u-TFF3 和 u-Cys)增加。这些发现提示在无临床常用参数(eGFR、血清尿素和肾脏形态)改变的情况下存在早期肾小管损伤。

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