Gao Shang, Tian Renli
Department of Urology, General Hospital of Northern Theater Command, Shenyang, China.
Department of Graduate School, China Medical University, Shenyang, China.
Transl Androl Urol. 2024 Nov 30;13(11):2430-2438. doi: 10.21037/tau-24-379. Epub 2024 Nov 28.
Upper urinary tract calculi (UUTC) are major risk factors for renal insufficiency and nephrectomy with psychological distress, notably depression and anxiety, being common among affected patients. Depression and anxiety are associated with heightened neuroticism. Individuals with neuroticism frequently exhibit a range of urological disorders. Given the limited research on UUTC and neuroticism, this study aims to explore this relationship using Mendelian randomization (MR) analysis.
We assessed the effects of neuroticism and associated psychological traits on UUTC using a two-sample MR approach, primarily employing the inverse variance weighted (IVW) method, with additional analysis via MR-Egger and weighted median methods. To ensure robustness, we conducted sensitivity analyses using Cochran's Q test, MR-Egger intercept, and MR-pleiotropy residual sum and outlier (PRESSO). At the same time, we selected the neuroticism score for verification queue of the exposure. Furthermore, to explore the independent effects of neuroticism traits on UUTC, we performed multivariable MR analyses on phenotypes with no pleiotropy, IVW P values below 0.05, and consistent directions across all three MR methods.
Our MR analysis revealed a significant causal impact of neuroticism on UUTC using the IVW [odds ratio (OR) =1.15, 95% confidence interval (CI): 1.02 to 1.29, P=0.03) and weighted median (OR =1.22, 95% CI: 1.03 to 1.44, P=0.02) methods. Verification queue similarly confirmed that the neuroticism score was a risk factor for UUTC (IVW, OR =1.11, 95% CI: 1.03 to 1.19, P=0.007). Sensitivity analyses indicated no heterogeneity or pleiotropy. Additionally, IVW analyses identified experiencing mood swings (OR =1.41, P=0.047), feeling lonely (OR =6.03, P<0.001), and feeling worry (OR =1.58, P=0.03) as significantly associated with UUTC. Multivariate MR analysis showed that experiencing mood swings is a stand-alone risk factor for UUTC (OR =1.75, P=0.03).
Our MR analysis has pinpointed neuroticism as a risk factor for UUTC, with experiencing mood swings identified as an independent risk factor for UUTC, offering new insights into the brain-kidney connection. The exact pathways driving this relationship require further study. These results highlight the necessity of vigilant urinary stone surveillance in individuals exhibiting neurotic traits.
上尿路结石（UUTC）是导致肾功能不全和肾切除术的主要危险因素，心理困扰，尤其是抑郁和焦虑，在受影响的患者中很常见。抑郁和焦虑与神经质增加有关。神经质的个体经常表现出一系列泌尿系统疾病。鉴于关于UUTC和神经质的研究有限，本研究旨在使用孟德尔随机化（MR）分析来探索这种关系。
我们使用两样本MR方法评估神经质及相关心理特征对UUTC的影响，主要采用逆方差加权（IVW）方法，并通过MR-Egger和加权中位数方法进行额外分析。为确保稳健性，我们使用Cochran's Q检验、MR-Egger截距和MR多效性残差和异常值（PRESSO）进行敏感性分析。同时，我们选择神经质评分用于暴露验证队列。此外，为了探索神经质特征对UUTC的独立影响，我们对无多效性、IVW P值低于0.05且在所有三种MR方法中方向一致的表型进行多变量MR分析。
我们的MR分析显示，使用IVW[比值比（OR）=1.15，95%置信区间（CI）：1.02至1.29，P = 0.03]和加权中位数（OR = 1.22，95%CI：1.03至1.44，P = 0.02）方法时，神经质对UUTC有显著的因果影响。验证队列同样证实神经质评分是UUTC的危险因素（IVW，OR = 1.11，95%CI：1.03至1.19，P = 0.007）。敏感性分析表明没有异质性或多效性。此外，IVW分析确定情绪波动（OR = 1.41，P = 0.047）、感到孤独（OR = 6.03，P < 0.001）和感到担忧（OR = 1.58，P = 0.03）与UUTC显著相关。多变量MR分析表明情绪波动是UUTC的独立危险因素（OR = 1.75，P = 0.03）。
我们的MR分析已确定神经质是UUTC的危险因素，情绪波动被确定为UUTC的独立危险因素，为脑-肾联系提供了新见解。驱动这种关系的确切途径需要进一步研究。这些结果突出了对表现出神经质特征的个体进行警惕的尿路结石监测的必要性。
