Lifestyle factors, serum parameters, metabolic comorbidities, and the risk of kidney stones: a Mendelian randomization study

Minghui Liu; Jian Wu; Meng Gao; Yongchao Li; Weiping Xia; Youjie Zhang; Jinbo Chen; Zhiyong Chen; Zewu Zhu; Hequn Chen

doi:10.3389/fendo.2023.1240171

Lifestyle factors, serum parameters, metabolic comorbidities, and the risk of kidney stones: a Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Sep 22:14:1240171. doi: 10.3389/fendo.2023.1240171. eCollection 2023.

Authors

Minghui Liu^{1

2}, Jian Wu^{1

2}, Meng Gao^{1

2}, Yongchao Li^{1

2}, Weiping Xia^{1

2}, Youjie Zhang^{1

2}, Jinbo Chen^{1

2}, Zhiyong Chen^{1

2}, Zewu Zhu^{1

2

3}, Hequn Chen^{1

2}

Affiliations

¹ Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Internal Medicine, Section Endocrinology, Yale University School of Medicine, New Haven, CT, United States.

Abstract

Background and objective: The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways.

Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones.

Results: The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%).

Conclusion: This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.

Keywords: Mendelian randomization; kidney stones; lifestyle factors; mediation Mendelian randomization; metabolic comorbidities.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Creatinine
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / etiology
Humans
Kidney Calculi* / etiology
Kidney Calculi* / genetics
Mendelian Randomization Analysis
Potassium
Sodium

Substances

Creatinine
Potassium
Sodium

Grants and funding

The study was supported by Fundamental Research Funds for the Central Universities of Central South University (2022ZZTS0294 to ML; 2021zzts0348 to ZZ), the National Natural Science Foundation of China (82170781 to HC), and the Natural Science Foundation of Hunan Province (2021JJ31050 to HC).