Associations of systemic inflammatory regulators with CKD and kidney function: evidence from the bidirectional mendelian randomization study

TL;DR

This study finds causal links between systemic inflammatory regulators and chronic kidney disease or kidney function using genetic data.

Contribution

The study provides causal evidence for the role of inflammatory regulators in kidney disease using bidirectional Mendelian randomization.

Findings

Eleven systemic inflammatory regulators showed suggestive associations with CKD or kidney function.

CKD was causally linked to granulocyte-colony stimulating factor and stem cell factor.

eGFRcys was causally associated with several inflammatory regulators like GCSF, IFNg, and VEGF.

Abstract

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.

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.

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).

Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.

The online version contains supplementary material available at 10.1186/s12882-024-03590-2.

Figures