Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study
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Updated: Jun 26, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Hailang Liu1, Wei Xiang1, Wei Wu1
1Department of Urology, Wuhan Integrated TCM & Western Medicine Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan No.1 Hospital, Wuhan, China.
Insights
This study used Mendelian randomization to investigate causal links between inflammatory regulators and chronic kidney disease (CKD). Findings support a causal relationship between these factors and CKD or kidney function.
Area of Science:
- Genetics
- Nephrology
- Immunology
Background:
- Observational studies suggest a link between systemic inflammation and chronic kidney disease (CKD).
- The causal nature of this association has remained unclear.
- Investigating causal relationships is crucial for understanding CKD development.
Purpose of the Study:
- To determine the potential causal relationships between 41 systemic inflammatory regulators and CKD.
- To assess the impact of these regulators on kidney function, including estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN).
- To explore bidirectional causal associations using Mendelian randomization.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analyses were employed.
- Inverse-variance weighting (IVW) was the primary analysis method.
- Sensitivity analyses included MR-PRESSO and weighted median tests to ensure robustness.
Main Results:
- Forward analyses identified 12 suggestive associations between 11 inflammatory regulators and CKD or kidney function.
- Significant causal associations were found in reverse analyses, including CKD with granulocyte-colony stimulating factor (GCSF) and stem cell factor (SCF).
- Specific regulators like SCF, GCSF, interferon gamma (IFNg), and vascular endothelial growth factor (VEGF) showed causal links with eGFRcrea and eGFRcys.
Conclusions:
- The study provides evidence supporting causal links between systemic inflammatory regulators and CKD.
- Causal associations were observed in both forward and reverse Mendelian randomization analyses.
- These findings highlight the role of specific inflammatory markers in kidney disease pathogenesis.
Background:
Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function.
Method:
We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test.
Results:
The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW β = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW β = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10- 6), eGFRcrea with SCF (IVW β =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10- 8), eGFRcys with GCSF (IVW β =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW β =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW β =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10- 4).
Conclusions:
Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.
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