bstantial interaction. Although observational studies have suggested a potential for enhanced CKD risk after prior kidney stones, the exact relationship remains ambiguous. Methods Shared comorbidities between two diseases were identified using unbiased screening. Genome-wide association study summary statistics were obtained from the UK Biobank (UKBB), FinnGen, and CKDGen, followed by genetic association analyses across various traits. Bidirectional Mendelian randomization (MR) analyses were performed to define causal links, complemented by multivariable MR that included the shared comorbidities including hypertension, diabetes, and obesity. Observational analyses were undertaken using cohorts from the Mayo Clinic and a UKBB subset. Results Despite identifying a total of 123 conditions as shared comorbidities, there was no significant genetic correlation between kidney stones and CKD. Unadjusted MR analysis revealed no significant association between kidney stones and CKD risk (UKBB [exposure]/FinnGen [outcome]: odds ratio [OR]=0.97, 95% confidence interval [CI], 0.88 to 1.06; FinnGen/UKBB: OR=1.17, 95% CI, 0.98 to 1.39). Kidney stones did significantly associate with a higher urinary albumin-creatinine ratio (β=0.014, 95% CI, 0.002 to –0.025), but this association disappeared in the multivariable MR model (β=0.009, 95% CI, −0.003 to 0.020). Furthermore, in a cross-sectional analysis limited to the UKBB cohort, a robust regression model did not detect an independent association between kidney stones and urinary albumin-creatinine ratio (β=0.16, 95% CI, −0.04 to 0.35) or eGFR (β=0.10, 95% CI, −0.07 to 0.28). Conversely, CKD associated with a diminished risk of kidney stones in multivariable MR models (UKBB/FinnGen: OR=0.77, 95% CI, 0.69 to 0.87; FinnGen/UKBB: OR=0.73, 95% CI, 0.66 to 0.81). Furthermore, in the Mayo Clinic cohort with available urinary biochemistries, lower eGFR was associated with lower urinary calcium excretion and urinary calcium oxalate/phosphate supersaturation. Conclusions In this study, kidney stones were not independently associated with CKD. Conversely, CKD was associated with a lower risk of calcium kidney stones likely via changes in key urinary traits, including lower calcium excretion....

中文翻译：

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肾结石与 CKD 之间的关联：一项双向孟德尔随机化研究


bstantial 交互。尽管观察性研究表明，既往肾结石后 CKD 风险可能增加，但确切的关系仍不明确。方法 使用无偏倚筛查确定两种疾病之间的共同合并症。全基因组关联研究摘要统计数据来自英国生物样本库 （UKBB）、FinnGen 和 CKDGen，然后是各种性状的遗传关联分析。进行双向孟德尔随机化 （MR） 分析以确定因果关系，并辅以包括高血压、糖尿病和肥胖等共同合并症的多变量 MR。使用来自 Mayo Clinic 和 UKBB 子集的队列进行观察分析。结果 尽管共有 123 种疾病被确定为共同的合并症，但肾结石与 CKD 之间没有显着的遗传相关性。未经调整的 MR 分析显示肾结石与 CKD 风险之间没有显著关联 （UKBB [暴露]/FinnGen [结局]：比值比 [OR]=0.97,95% 置信区间 [CI]，0.88 至 1.06;FinnGen/UKBB：OR=1.17,95% CI，0.98 至 1.39）。肾结石确实与较高的尿白蛋白-肌酐比值显著相关 （β=0.014,95% CI，0.002 至 -0.025），但这种关联在多变量 MR 模型中消失了 （β=0.009,95% CI，-0.003 至 0.020）。此外，在仅限于 UKBB 队列的横断面分析中，稳健回归模型未检测到肾结石与尿白蛋白-肌酐比值 （β=0.16,95% CI，-0.04 至 0.35）或 eGFR （β=0.10,95% CI，-0.07 至 0.28）之间的独立关联。相反，在多变量 MR 模型中，CKD 与肾结石风险降低相关 （UKBB/FinnGen： OR=0.77,95% CI，0.69 至 0.87;FinnGen/UKBB：OR=0。73,95% CI，0.66 至 0.81）。此外，在具有可用尿液生化指标的 Mayo Clinic 队列中，较低的 eGFR 与较低的尿钙排泄和尿草酸钙/磷酸盐过饱和度相关。结论 在本研究中，肾结石与 CKD 不独立相关。相反，CKD 与钙肾结石风险降低有关，这可能是由于关键尿液特征的变化，包括钙排泄量降低。