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Urolithiasis
Published in: Urolithiasis 1/2023

01-12-2023 | Research

Kidney function may partially mediated the protective effect of urinary uromodulin on kidney stone

Authors: Zhongyu Jian, Chi Yuan, Zheyu Xiong, Hong Li, Xi Jin, Kunjie Wang

Published in: Urolithiasis | Issue 1/2023

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Abstract

The causal links between urinary uromodulin (uUMOD) and kidney stone disease (KSD) are still not clarified in general population. We assessed their relationships combining 2-sample Mendelian randomization (MR) and multivariable (MVMR) designs among general population of European ancestry. The summary information for uUMOD indexed to creatinine levels (29,315 individuals) and KSD (395,044 individuals) were from 2 independent genome-wide association studies (GWAS). The primary causal effects of exposures on outcomes were evaluated using inverse variance-weighted (IVW) regression model. Multiple sensitivity analyses were also performed. In 2-sample MR, we found that 1-unit higher genetically predicted uUMOD levels were associated with a lower risk of KSD (OR = 0.62; 95% CI 0.55–0.71; P = 2.83E−13). In reverse, we did not find the effect of KSD on uUOMD using IVW (beta = 0.00; 95% CI − 0.06–0.05; P = 0.872) and other sensitivity analyses. In MVMR, uUMOD indexed to creatinine levels were directly associated with the risk of KSD after introducing eGFR, SBP, urinary sodium or all three factors (OR = 0.71; 95% CI 0.64–0.79; P = 1.57E−09). Furthermore, our study supported that the protective effect of uUMOD on KSD may be partially mediated by eGFR (beta = − 0.09; 95% CI − 0.13 to − 0.06; mediation proportion = 20%). Our study supported that the protective effect of genetically predicted higher uUMOD levels on KSD may be partially mediated by eGFR decline, but not via SBP or urinary sodium. uUMOD might be a treatment target in preventing KSD in general population.
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Metadata
Title
Kidney function may partially mediated the protective effect of urinary uromodulin on kidney stone
Authors
Zhongyu Jian
Chi Yuan
Zheyu Xiong
Hong Li
Xi Jin
Kunjie Wang
Publication date
01-12-2023
Publisher
Springer Berlin Heidelberg
Published in
Urolithiasis / Issue 1/2023
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI
https://doi.org/10.1007/s00240-023-01441-7

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