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IF 2 2区医学 Q2 UROLOGY & NEPHROLOGY

Urolithiasis Pub Date : 2025-04-01 DOI:10.1007/s00240-025-01738-9

Haotian Huang, Zhi Wen, Hongyuan Li, Chongjian Wang, Caixia Chen, Yang Liu, Jiao Qin, Song Cao, Xuesong Yang

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引用次数: 0

摘要

泌尿系统结石是一种以代谢循环问题和持续炎症为特征的全身性疾病。本研究的目的是探索血浆代谢物、生物标志物、炎症蛋白和泌尿系统结石之间的因果关系。我们首先进行了双样本孟德尔随机化（MR）分析，评估了233种血浆代谢物和35种与尿路结石相关的生物标志物之间可能存在的因果关系。有关血浆代谢物的遗传关联研究（GWAS）数据来自 2024 年发表在《自然》杂志上的一篇文章，而生物标志物的数据则来自英国生物库。为了确定因果关系，我们采用了多种分析技术，包括逆方差加权（IVW）、MR-Egger、加权中位数和加权模式。此外，我们还进行了多向性和异质性分析，以确保研究结果的稳健性。我们还使用了 Steiger 分析来探讨是否存在反向因果关系。最后，我们进行了中介分析，以阐明炎症蛋白是如何中介血浆代谢物、生物标志物和泌尿系统结石之间的关联的。我们的研究表明，六种血浆代谢物和六种与上尿路结石有关的生物标志物之间存在因果关系。此外，我们还发现了十种血浆代谢物与四种与下尿路结石有关的生物标志物之间的因果关系。这些代谢物大多属于脂质和脂蛋白类，表明血脂水平的变化可能会影响结石的形成。最后，中介分析显示了13种中介关系，包括六种炎症蛋白的中介效应。我们的研究结果提供了血浆代谢物、生物标志物和炎症蛋白之间与尿路结石相关的因果联系的证据。这为了解泌尿系统结石形成的潜在机制提供了新的视角，有助于结石的预防、诊断和治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Effect of the plasma metabolites, biomarkers, and inflammatory proteins on urolithiasis: insights from Mendelian randomization and mediation analysis.

Urolithiasis represents a systemic disorder characterized by metabolic circulation issues and ongoing inflammation. The purpose of this research is to explore the relationships of causation among plasma metabolites, biomarkers, inflammatory proteins, and stones within the urinary system. We initially carried out a two-sample Mendelian randomization (MR) analysis to evaluate possible causal connections between 233 plasma metabolites and 35 biomarkers related to urolithiasis. The genetic association study (GWAS) data concerning plasma metabolites were derived from a 2024 publication in Nature, while data for biomarkers were collected from the UK Biobank. To determine causal relationships, we utilized several analytical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Furthermore, we conducted analyses for pleiotropy and heterogeneity to ensure the findings' robustness. A Steiger analysis was used to explore the presence of any reverse causal relationships. Lastly, we conducted mediation analysis to elucidate how inflammatory proteins mediate the associations between plasma metabolites, biomarkers, and stones in the urinary system. Our research demonstrates causal connections between six plasma metabolites and six biomarkers related to upper urinary tract stones. Furthermore, we identified causal associations between ten plasma metabolites and four biomarkers linked to lower urinary tract stones. Most of these metabolites belong to lipid and lipoprotein classes, indicating that changes in blood lipid levels may influence stone formation. Finally, mediation analysis revealed 13 mediating relationships, including the mediating effects of six inflammatory proteins. Our results provide evidence for the causal links among plasma metabolites, biomarkers, and inflammatory proteins associated with urolithiasis. This provides new insights into the potential mechanisms underlying urinary system stone formation, contributing to their prevention, diagnosis, and treatment.

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来源期刊

Urolithiasis UROLOGY & NEPHROLOGY-

CiteScore

4.50

自引率

6.50%

发文量

期刊介绍： Official Journal of the International Urolithiasis Society The journal aims to publish original articles in the fields of clinical and experimental investigation only within the sphere of urolithiasis and its related areas of research. The journal covers all aspects of urolithiasis research including the diagnosis, epidemiology, pathogenesis, genetics, clinical biochemistry, open and non-invasive surgical intervention, nephrological investigation, chemistry and prophylaxis of the disorder. The Editor welcomes contributions on topics of interest to urologists, nephrologists, radiologists, clinical biochemists, epidemiologists, nutritionists, basic scientists and nurses working in that field. Contributions may be submitted as full-length articles or as rapid communications in the form of Letters to the Editor. Articles should be original and should contain important new findings from carefully conducted studies designed to produce statistically significant data. Please note that we no longer publish articles classified as Case Reports. Editorials and review articles may be published by invitation from the Editorial Board. All submissions are peer-reviewed. Through an electronic system for the submission and review of manuscripts, the Editor and Associate Editors aim to make publication accessible as quickly as possible to a large number of readers throughout the world.