Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Am J Kidney Dis. 2021 Aug;78(2):210-218. doi: 10.1053/j.ajkd.2020.11.018. Epub 2021 Jan 2.
RATIONALE & OBJECTIVE: The association between hyperuricemia and urolithiasis has been previously reported. However, this association is based on observational data, which are prone to residual confounding. The aim of this work was to use Mendelian randomization (MR) to evaluate if this relationship represents a causal effect of hyperuricemia.
MR analysis using 2 approaches: 2-stage MR and 2-sample MR.
SETTING & PARTICIPANTS: Participants aged 40-69 years from the UK Biobank Resource.
Serum urate.
Urolithiasis.
An observational analysis testing for an association between serum urate level and urolithiasis was performed using logistic regression. For MR analyses, serum urate-associated single-nucleotide polymorphisms, identified from genome-wide association data, were used as instrumental variables for serum urate. In the 2-stage MR analysis, a weighted genetic urate score was calculated from the instrumental variables, and a control function estimation model was fit. In the 2-sample MR analysis, multiple-instrument MR via the inverse-variance weighted method was performed.
Individual-level data were available for 359,827 participants, of whom 6,398 (1.8%) reported urolithiasis. In the observational analysis, serum urate was positively associated with urolithiasis in an unadjusted analysis (odds ratio [OR], 1.47 [95% CI, 1.42-1.51]); however, after adjustment for relevant confounders, no association was observed (OR, 1.03 [95% CI, 0.99-1.08]). In the 2-stage MR analysis, no significant causal effect of serum urate level on urolithiasis was observed in the unadjusted (OR, 0.93 [95% CI, 0.81-1.08]) or adjusted (OR, 0.94 [95% CI, 0.80-1.09]) models. In the 2-sample MR analysis, multiple-instrument MR did not indicate a causal effect of serum urate on urolithiasis.
Stone composition and urinalysis data, including urine pH, were not available for this study.
Our analyses do not support a causal effect of serum urate level on urolithiasis. The association between serum urate level and urolithiasis reported in observational studies is likely due to residual confounding.
高尿酸血症与尿路结石之间的关联此前已有报道。然而，这种关联基于观察性数据，而观察性数据容易受到残余混杂因素的影响。本研究旨在使用孟德尔随机化（MR）来评估这种关系是否代表高尿酸血症的因果效应。
使用两种方法进行 MR 分析：两阶段 MR 和两样本 MR。
来自英国生物库资源的年龄在 40-69 岁的参与者。
血清尿酸。
尿路结石。
使用逻辑回归对血清尿酸水平与尿路结石之间的关联进行了观察性分析。对于 MR 分析，使用全基因组关联数据确定的与血清尿酸相关的单核苷酸多态性作为血清尿酸的工具变量。在两阶段 MR 分析中，从工具变量中计算加权遗传尿酸评分，并拟合控制函数估计模型。在两样本 MR 分析中，通过逆方差加权法进行多变量 MR。
共有 359827 名参与者提供了个体水平数据，其中 6398 名（1.8%）报告患有尿路结石。在未调整分析中，血清尿酸与尿路结石呈正相关（比值比[OR]，1.47[95%置信区间，1.42-1.51]）；然而，在调整了相关混杂因素后，未观察到相关性（OR，1.03[95%置信区间，0.99-1.08]）。在两阶段 MR 分析中，在未调整（OR，0.93[95%置信区间，0.81-1.08]）或调整（OR，0.94[95%置信区间，0.80-1.09]）模型中，血清尿酸水平对尿路结石无显著因果效应。在两样本 MR 分析中，多变量 MR 并未表明血清尿酸对尿路结石有因果影响。
本研究未提供结石成分和尿分析数据，包括尿 pH 值。
我们的分析不支持血清尿酸水平对尿路结石的因果效应。在观察性研究中报告的血清尿酸水平与尿路结石之间的关联可能是由于残余混杂因素所致。
