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Genetically Predicted Associations of CX3CL1 and UMOD with Acute Kidney Injury Risk: Evidence from Mendelian
Liu Yang1, Yan Xu2, Yan Liang3
1Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Journal of Inflammation Research
|July 15, 2026
Summary
Two plasma proteins, CX3CL1 and uromodulin (UMOD), show a causal link to acute kidney injury (AKI) risk. These proteins may aid in understanding AKI and developing targeted therapies.
Area of Science:
- Genetics
- Proteomics
- Nephrology
Background:
- Acute kidney injury (AKI) presents a significant clinical challenge with limited therapeutic options.
- Identifying genetically supported protein biomarkers is crucial for understanding AKI pathogenesis.
Purpose of the Study:
- To systematically identify proteins causally linked to AKI risk using genetic data.
- To explore biological pathways and phenotypic associations of candidate proteins.
- To evaluate CX3CL1 and UMOD as potential diagnostic markers for AKI.
Main Methods:
- Utilized large-scale genetic and proteomic databases (UKB-PPP, FinnGen, IEU Open GWAS).
- Applied Mendelian randomization (SMR, two-sample MR), colocalization, mediation, and phenome-wide association studies (PheWAS).
- Measured plasma CX3CL1 and UMOD levels in patients with ischemia-reperfusion (I/R) induced AKI.
Main Results:
- CX3CL1 and uromodulin (UMOD) were identified as positively and causally associated with AKI risk.
- CX3CL1's effect on AKI may be mediated by metabolites; PheWAS linked proteins to hypertension, metabolic disorders, and infections.
- Elevated plasma CX3CL1 and UMOD levels were observed in I/R-induced AKI patients, correlating with serum creatinine.
Conclusions:
- CX3CL1 and UMOD are genetically supported candidate proteins for AKI.
- These findings enhance understanding of AKI pathogenesis and inform drug development safety.
- CX3CL1 and UMOD show potential diagnostic utility for AKI, with high specificity.
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