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Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study

  • Urology – Original Paper
  • Published:
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Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis.


In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results.


91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01–1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00–1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78–0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88–0.98), STAM-binding protein (OR 0.83, 95% CI 0.69–0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger’s intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05.


Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD.

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Data availability

The original contributions presented in this study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.



Kidney stone disease


Neutrophil-to-lymphocyte ratio


Percutaneous nephrolithotomy


Fibroblast growth factor 5


STAM-binding protein


Genome-wide association studies


Instrumental variable


Inverse variance weighted


Mendelian randomization


MR-Pleiotropy Residual Sum and Outlier method


Odds ratio


Single nucleotide polymorphism


Delta and Notch-like epidermal growth factor-related receptor


Macrophage inflammatory protein 1α


Renal tubular epithelial cells


Monocyte chemoattractant protein 1


Colony-stimulating factor 1


CD5 antigen-like


Short chain fatty acids


Potassium sodium hydrogen citrate


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We express our gratitude to all SCALLOP Consortium studies for providing open access to the summary association statistics data. Genetic association estimates for kidney stone disease were obtained from the FinnGen consortium ( We thank all investigators for sharing these data.


This work was supported by the National Natural Science Foundation of China (Grant No. 81974092).

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Authors and Affiliations



D.F. Yuan and J.Y. Yang prepared and drafted the manuscript. X. Yu obtained funding for the study and provided critical revision of the manuscript for important intellectual content. W.S. Wu, Y. Amier, X.M. Li, and W.L. Wan assisted in obtaining data for the review article and revised the manuscript. Y.S. Huang and J.B. Li confirmed the authenticity of all the raw data.

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Correspondence to Xiao Yu.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Our analysis used publicly available GWAS summary statistics. No new data were collected, and no new ethical approval was required.

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Yuan, D., Yang, J., Wu, W. et al. Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study. Int Urol Nephrol (2024).

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