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

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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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Data availability

All data generated or analyzed during this study are included in this published article and its Supplementary information files.

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Funding

This study was supported by the Foundation of Science & Technology Department of Sichuan Province [2021YFS0116, 2022YFS0304] and the Post-Doctor Research Project, West China Hospital, Sichuan University, Grant/Award Number: 2020HXBH016.

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Author notes

  1. Zhongyu Jian and Chi Yuan have contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, People’s Republic of China

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

  2. West China Biomedical Big Data Center, Sichuan University, Chengdu, People’s Republic of China

    Zhongyu Jian

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  1. Zhongyu Jian
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  2. Chi Yuan
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  5. Xi Jin
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  6. Kunjie Wang
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Contributions

Conceptualization and original draft preparation: ZJ and CY. Data collection: ZX. Data analysis: HL. Resources and supervision: XJ and KW. All authors read and agreed to the published version of the manuscript.

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Correspondence to Xi Jin or Kunjie Wang.

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Jian, Z., Yuan, C., Xiong, Z. et al. Kidney function may partially mediated the protective effect of urinary uromodulin on kidney stone. Urolithiasis 51, 65 (2023). https://doi.org/10.1007/s00240-023-01441-7

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