Department of Urology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
School of Basic Medical Sciences, Peking University, Beijing, China.
Front Endocrinol (Lausanne). 2023 Dec 1;14:1301163. doi: 10.3389/fendo.2023.1301163. eCollection 2023.
Previous studies have yielded conflicting findings regarding the association between circulating lipids and lipid-lowering drugs with urinary stones, and the causal relationship between the two remains inconclusive.
This study aimed to assess the causal relationship between circulating lipids (Triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], apolipoprotein A [APOA], apolipoprotein B [APOB] and Pure hypercholesterolaemia), lipid-lowering drugs (HMGCR [HMG-CoA reductase] inhibitors and PCSK9[Proprotein Convertase Subtilisin/Kexin Type 9] inhibitors) and the risk of urinary stones, using genetic data.
Genetic instrumental variables (GIVs) for circulating lipids and lipid-lowering drugs were obtained from the UK Biobank and existing literature. Outcome data were extracted from a genetic association database with 3,625 urinary stone cases and 459,308 controls. Two-sample MR analysis, employing the TwoSampleMR software package in R 4.2.3, was conducted to assess the associations between multiple exposures. The primary outcome was determined using the inverse variance weighted (IVW) method for the causal relationship between exposure and outcome, while additional methods such as MR-Egger, weighted median, simple mode, and weighted mode were utilized as supplementary analyses. Robustness of the Mendelian Randomization (MR) analysis results was assessed through leave-one-out analysis and funnel plots.
The MR analysis revealed a significant association between elevated TG levels per 1 standard deviation and the occurrence of urinary stones (odds ratio [OR]: 1.002, 95% confidence interval [CI]: 1.000-1.003, P = 0.010). However, no significant association was observed between factors other than TG exposure and the risk of urinary stone occurrence across all methods(LDL-C: [OR], 1.001; 95% [CI], 1.000-1.003, P=0.132;HDL-C: [OR], 0.999; 95% [CI], 0.998-1.000, P=0.151;APOA:[OR] being 1.000 (95% [CI], 0.999-1.001, P=0.721;APOB: [OR] of 1.001 (95% [CI], 1.000-1.002, P=0.058;Pure hypercholesterolaemia: [OR] of 1.015 (95% [CI], 0.976-1.055, P=0.455) and lipid-lowering drugs (HMGCR inhibitors: [OR], 0.997; 95% [CI], 0.990-1.003, P=0.301 and PCSK9 inhibitors:[OR], 1.002; 95% [CI], 1.000-1.005, P=0.099).
Our findings provide conclusive evidence supporting a causal relationship between an increased risk of urinary stones and elevated serum TG levels. However, we did not find a significant association between urinary stone occurrence and the levels of LDL-C, HDL-C, APOA, APOB, Pure hypercholesterolaemia and lipid-lowering drugs.
先前的研究在循环脂质和降脂药物与尿路结石之间的关联方面得出了相互矛盾的结果，两者之间的因果关系仍不确定。
本研究旨在使用遗传数据评估循环脂质（甘油三酯[TG]、低密度脂蛋白胆固醇[LDL-C]、高密度脂蛋白胆固醇[HDL-C]、载脂蛋白 A [APOA]、载脂蛋白 B [APOB]和纯高胆固醇血症）、降脂药物（HMGCR[HMG-CoA 还原酶]抑制剂和 PCSK9[蛋白水解酶 9]抑制剂）与尿路结石风险之间的因果关系。
从英国生物银行和现有文献中获得了循环脂质和降脂药物的遗传工具变量（GIV）。从一个具有 3625 例尿路结石病例和 459308 例对照的遗传关联数据库中提取了结果数据。使用 R 4.2.3 中的 TwoSampleMR 软件包进行两样本 MR 分析，以评估多种暴露因素之间的关联。主要结果是使用暴露与结局之间的逆方差加权（IVW）方法来确定因果关系，同时还使用 MR-Egger、加权中位数、简单模式和加权模式等其他方法作为补充分析。通过单样本缺失分析和漏斗图评估 Mendelian Randomization（MR）分析结果的稳健性。
MR 分析表明，血清 TG 水平每升高 1 个标准差与尿路结石的发生呈显著正相关（优势比[OR]：1.002，95%置信区间[CI]：1.000-1.003，P=0.010）。然而，在所有方法中，除了 TG 暴露之外的其他因素与尿路结石发生风险之间没有显著关联（LDL-C：[OR]，1.001；95%[CI]，1.000-1.003，P=0.132；HDL-C：[OR]，0.999；95%[CI]，0.998-1.000，P=0.151；APOA：[OR]为 1.000（95%[CI]，0.999-1.001，P=0.721；APOB：[OR]为 1.001（95%[CI]，1.000-1.002，P=0.058；纯高胆固醇血症：[OR]为 1.015（95%[CI]，0.976-1.055，P=0.455）和降脂药物（HMGCR 抑制剂：[OR]，0.997；95%[CI]，0.990-1.003，P=0.301 和 PCSK9 抑制剂：[OR]，1.002；95%[CI]，1.000-1.005，P=0.099）。
我们的研究结果提供了确凿的证据，支持血清 TG 水平升高与尿路结石风险增加之间存在因果关系。然而，我们没有发现 LDL-C、HDL-C、APOA、APOB、纯高胆固醇血症和降脂药物与尿路结石发生之间存在显著关联。
