AUTHOR=Huang Yong , Wang Hexi , Xu Chengwei , Zhou Fulin , Su Huiyi , Zhang Yao 

TITLE=Associations between smoke exposure and kidney stones: results from the NHANES (2007–2018) and Mendelian randomization analysis

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1218051

DOI=10.3389/fmed.2023.1218051

ISSN=2296-858X

ABSTRACT=Purpose: Whether smoke exposure is associated with the risk of kidney stones is currently controversial. Herein, publicly available databases were combined to explore relationships with the risk of nephrolithiasis in terms of smoking status and serum cotinine concentrations. Materials and methods: First, we conducted an observational study using data from 2007 to 2018, based on the National Health and Nutrition Examination Survey (NHANES) database. Univariate analysis, multivariate logistic regression, trend testing, restricted cubic spline (RCS) and multiple imputation (MI) were main analytical methods of our study. Then, Mendelian randomization (MR) analysis was performed to explore the causal relationship between serum cotinine and nephrolithiasis. Genetic instruments for serum cotinine and pooled data for kidney stones were derived from publicly available large-scale genome-wide association studies (GWAS). Inverse variance weighted (IVW) was the primary method for our MR analysis. Results: A total of 34657 and 31352 participants were included in the observational study based on smoking status and serum cotinine concentrations, respectively. Under full adjustment of covariates, current smokers had an increased risk of kidney stones compared to non smokers [OR = 1.17 (1.04-1.31), P = 0.009, P for trend = 0.010]. Compared with serum cotinine < 0.05 ng/ml, serum cotinine levels of 0.05-2.99 ng/ml [OR = 1.15 (1.03-1.29), P = 0.013] and ≥ 3.00 ng/ml [OR = 1.22 (1.10-1.37), P < 0.001] were observed to have a higher risk of nephrolithiasis (P for trend < 0.001). Besides, a nonlinear relationship between log2 transformed serum cotinine and the risk of nephrolithiasis was found (P for non-linearity = 0.028). Similar results were found when serum cotinine (log2 transformation) was used as a continuous variable [OR = 1.02 (1.01-1.03), P < 0.001] or complete data was used to analysis after MI. In MR analysis, genetically predicted high serum cotinine was causally related to the high risk of nephrolithiasis [IVW: OR = 1.09 (1.00-1.19), P = 0.044].Current smokers and high serum cotinine concentrations might be associated with an increased risk of kidney stones. Further research is needed to validate their relationship and explore underlying mechanisms.