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Kidney Week

Abstract: PO2249

Genetic Determinants of Interleukin-6 Levels and Risk of ESRD

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Wheless, Lee, Vanderbilt University, Nashville, Tennessee, United States
  • Pike, Mindy, Vanderbilt University, Nashville, Tennessee, United States
  • Chen, Hua-Chang, Vanderbilt University, Nashville, Tennessee, United States
  • Tao, Ran, Vanderbilt University, Nashville, Tennessee, United States
  • Shah, Shailja C., University of California San Diego, La Jolla, California, United States
  • Bick, Alexander, Vanderbilt University, Nashville, Tennessee, United States
  • Chung, Cecilia P., Vanderbilt University, Nashville, Tennessee, United States
  • Robinson-Cohen, Cassianne, Vanderbilt University, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University, Nashville, Tennessee, United States

Group or Team Name

  • Million Veteran Program
Background

Multiple observational studies indicate an association between circulating levels of interleukin-6 (IL-6) and end-stage renal disease (ESRD). However, these studies are prone to confounding and reverse causation, limiting their utility in identifying causal relationships. Mendelian Randomization (MR) studies can provide evidence for causality by examining the relationship between genetically-determined
biomarker levels and outcomes. We used MR to evaluate whether genetically predicted higher IL-6 levels are associated with the risk of ESRD.

Methods

We performed two-sample MR of the relationship between IL-6 and ESRD. We selected 5 single nucleotide polymorphisms (SNPs) robustly associated with IL-6 levels at genome-wide significance among 30,931 individuals in the SCALLOP consortium as instrumental variables and examined their association with the odds of ESRD in the Million Veteran Program (MVP) among 5,503 ESRD cases and 6,354 controls.

Results

A genetically-driven increase in IL-6 levels was associated with a 30% higher odds of ESRD (95% confidence interval [CI] 1.01 to 1.67; p = 0.04). In race stratified models, among 3,112 Caucasians and 3,170 controls, there was a weaker association (OR 1.17, 95% CI 0.86 – 1.59) compared to 2,062 African Americans (OR 1.30, 95% CI 0.83 – 2.04).

Conclusion

IL-6 levels might be causally associated with the risk of ESRD. This association was stronger among African Americans, although was underpowered. Additional studies are needed to clarify the role of IL-6 in ESRD, and if inhibition of this cytokine could be a target for delaying kidney disease progression to ESRD.
Co-seniors: Robinson Cohen & Hung

Funding

  • Veterans Affairs Support