探索肾损伤分子-1和HAVCR1基因多态性作为慢性肾脏病的预测生物标志物

Exploring Kidney Injury Molecule-1 and HAVCR1 Polymorphisms as Predictive Biomarkers in Chronic Kidney Disease.

作者信息

Chaiyagot Nachayada, Silsirivanit Atit, Cha'on Ubon, Jusakul Apinya, Techasen Anchalee, Nahok Kanokwan, Chamdam Angkor, Anutrakulchai Sirirat, Lert-Itthiporn Worachart

机构信息

Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Chronic Kidney Disease Prevention in Northeast Thailand: CKDNET, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Kidney Dis (Basel). 2025 Apr 14;11(1):342-355. doi: 10.1159/000545831. eCollection 2025 Jan-Dec.

Abstract

INTRODUCTION

Kidney injury molecule-1 (KIM-1), encoded by the Hepatitis A Virus Cellular Receptor 1 () gene, plays a crucial role in kidney injury progression. Although serum and urinary KIM-1 levels are established biomarkers for kidney damage, the relationship between KIM-1 levels, gene polymorphism, and chronic kidney disease (CKD) stages remains unclear. This study aimed to investigate KIM-1 as a potential biomarker for CKD progression in the Thai population and explore its association with genetic polymorphisms in the gene.

METHODS

A total of 250 patients with CKD were recruited from Khon Kaen, Thailand. Serum and urinary KIM-1 levels were measured using an indirect enzyme-linked immunosorbent assay. Single-nucleotide polymorphism (SNP) genotyping was conducted using the TaqMan assay to assess the associations between KIM-1 levels, SNPs, and CKD progression. Statistical analyses were conducted to assess the correlations between estimated glomerular filtration rate (eGFR), KIM-1 levels, and SNPs.

RESULTS

Serum and urinary KIM-1 levels showed a significant negative correlation with eGFR, indicating higher KIM-1 levels in patients with more advanced CKD. However, the rs6555820 SNP in the gene did not show a significant association with KIM-1 levels or eGFR. Interestingly, a significant association between rs6555820 and gender was observed, implying a potential gender-dependent genetic impact.

CONCLUSION

Serum and urinary KIM-1 levels have been found to be associated with CKD stages and eGFR, suggesting their potential as biomarkers for assessing CKD severity. However, no direct associations were observed between the SNP rs6555820 and KIM-1 levels or eGFR. Further research is required to elucidate the genetic mechanisms underlying CKD progression.

摘要

引言

由甲型肝炎病毒细胞受体1(HAVCR1)基因编码的肾损伤分子-1(KIM-1)在肾损伤进展中起关键作用。尽管血清和尿液中的KIM-1水平是已确立的肾损伤生物标志物,但KIM-1水平、HAVCR1基因多态性与慢性肾脏病(CKD)分期之间的关系仍不清楚。本研究旨在调查KIM-1作为泰国人群CKD进展潜在生物标志物的情况,并探讨其与HAVCR1基因遗传多态性的关联。

方法

从泰国孔敬招募了总共250例CKD患者。使用间接酶联免疫吸附测定法测量血清和尿液中的KIM-1水平。采用TaqMan测定法进行单核苷酸多态性(SNP)基因分型,以评估KIM-1水平、SNP与CKD进展之间的关联。进行统计分析以评估估计肾小球滤过率(eGFR)、KIM-1水平和SNP之间的相关性。

结果

血清和尿液中的KIM-1水平与eGFR呈显著负相关,表明CKD病情越严重的患者KIM-1水平越高。然而,HAVCR1基因中的rs6555820 SNP与KIM-1水平或eGFR未显示出显著关联。有趣的是,观察到rs6555820与性别之间存在显著关联,这意味着可能存在性别依赖性遗传影响。

结论

已发现血清和尿液中的KIM-1水平与CKD分期和eGFR相关,表明它们作为评估CKD严重程度生物标志物的潜力。然而,未观察到SNP rs6555820与KIM-1水平或eGFR之间存在直接关联。需要进一步研究以阐明CKD进展的遗传机制。

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