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造血干细胞移植后的急性肾损伤与肾小管生物标志物

[Acute kidney injury and tubular biomarkers after hematopoietic stem cell transplantation].

作者信息

Dobronravov V A, Smirnov K A, Afanasiev B V, Galkina O V, Smirnov A V

机构信息

I.P. Pavlov First Saint Petersburg Medical University, Ministry of Health of Russia, Saint Petersburg, Russia.

出版信息

Ter Arkh. 2016;88(6):14-20. doi: 10.17116/terarkh201688614-20.

Abstract

AIM

To determine the value of molecular biomarkers (BMs) associated with tubular epithelial damage in developing and predicting acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT).

SUBJECTS AND METHODS

The open-label observational prospective study enrolled 90 patients (46 males and 44 females) who had undergone HSCT. The concentrations of BMs (calbindin, clusterin, interleukin-18 (IL-18), kidney injury molecules-1 (KIM-1), glutathione S-transferase-π (GST-π), and monocyte chemoattractant protein-1 (MCP-1) were measured in urinary samples 7 days before HSCT (week 0) and at weeks 1, 2, 3, 4, and 5. Main clinical parameters were simultaneously monitored. AKI was diagnosed and stratified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines.

RESULTS

At weeks 1, 2, 3, 4, and 5 after HSCT, the proportion of AKI cases was 7.8, 8.9, 12.5, 27.3, and 35.9%, respectively. The elevated urinary levels of BMs (above the median) were found to be substantially more common than AKI cases. The urinary excretion of the majority of BMs dramatically increased in the early HSCT period. The median number of simultaneously elevated BMs was 3 (2; 5) during the entire follow-up period. Clusterin, MCP-1 and KIM-1 positively and significantly correlated with serum creatinine at the week following the determination of BMs in the multivariate linear regression models adjusted for other confounders. The higher urinary KIM-1 and/or MCP-1 excretion regardless of other clinical indicators was associated with the higher relative risk (RR) of AKI, which increased by 2.3 times with a rise in one of these indicators and by 3.4 times with a rise in both indicators.

CONCLUSION

Multiple renal toxic effects after HSCT result in a substantial and simultaneous elevation of urinary excretion of BMs for tubular damage. Among the BMs studied, KIM-1 and MCP-1 seem to be the most suitable molecules for assessing the risk of AKI in this cohort of patient within the predictive diagnostic approach.

摘要

目的

确定与造血干细胞移植(HSCT)后发生及预测急性肾损伤(AKI)相关的肾小管上皮损伤分子生物标志物(BMs)的价值。

对象与方法

这项开放标签的观察性前瞻性研究纳入了90例接受HSCT的患者(46例男性和44例女性)。在HSCT前7天(第0周)以及第1、2、3、4和5周时,检测尿样中BMs(钙结合蛋白、簇集素、白细胞介素-18(IL-18)、肾损伤分子-1(KIM-1)、谷胱甘肽S-转移酶-π(GST-π)和单核细胞趋化蛋白-1(MCP-1))的浓度。同时监测主要临床参数。根据改善全球肾脏病预后组织(KDIGO)指南对AKI进行诊断和分层。

结果

HSCT后第1、2、3、4和5周时,AKI病例的比例分别为7.8%、8.9%、12.5%、27.3%和35.9%。发现BMs尿水平升高(高于中位数)的情况比AKI病例更为常见。在HSCT早期,大多数BMs的尿排泄量显著增加。在整个随访期间,同时升高的BMs的中位数为3(2;5)。在针对其他混杂因素进行调整的多元线性回归模型中,簇集素、MCP-1和KIM-1在测定BMs后的第1周与血清肌酐呈正相关且具有显著相关性。无论其他临床指标如何,尿KIM-1和/或MCP-1排泄量较高与AKI的相对风险(RR)较高相关,其中一项指标升高时RR增加2.3倍,两项指标都升高时RR增加3.4倍。

结论

HSCT后的多种肾毒性作用导致肾小管损伤的BMs尿排泄量大幅同时升高。在所研究的BMs中,KIM-1和MCP-1似乎是在该患者队列的预测性诊断方法中评估AKI风险最合适的分子。

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