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

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

doi:10.3389/fendo.2023.1240171

Frontiers in Endocrinology (Sep 2023)

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

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

Affiliations

Minghui Liu: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Minghui Liu: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Jian Wu: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Jian Wu: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Meng Gao: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Meng Gao: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Yongchao Li: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Yongchao Li: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Weiping Xia: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Weiping Xia: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Youjie Zhang: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Youjie Zhang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Jinbo Chen: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Jinbo Chen: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Zhiyong Chen: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Zhiyong Chen: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Zewu Zhu: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Zewu Zhu: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Zewu Zhu: Department of Internal Medicine, Section Endocrinology, Yale University School of Medicine, New Haven, CT, United States
Hequn Chen: Department of Urology, Xiangya Hospital, Central South University, Changsha, China
Hequn Chen: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

DOI: https://doi.org/10.3389/fendo.2023.1240171
Journal volume & issue: Vol. 14

Abstract

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Background and objectiveThe 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.MethodsWe 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.ResultsThe 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%).ConclusionThis 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.

Published in Frontiers in Endocrinology

ISSN: 1664-2392 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the endocrine glands. Clinical endocrinology
Website: https://www.frontiersin.org/journals/endocrinology

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