#3913 GENETIC SUSCEPTIBILITY AS AN EFFECT MODIFIER FOR THE ASSOCIATION BETWEEN CHRONIC KIDNEY DISEASE AND RISK OF VENOUS THROMBOEMBOLISM

Abstract

Abstract Background and Aims The association between chronic kidney disease (CKD) and the risk of developing venous thromboembolism (VTE) is still controversial. Further, it is unknown if genetic predisposition modifies this relationship. This study was conducted to investigate plausible effect modification of genetic factors on the association between CKD and incident VTE. Method Population-based cohort study of the UK Biobank, including 397,658 participants of European ancestry that were free of VTE at recruitment. We used cystatin C combining creatinine estimated glomerular filtration rate (eGFR) and albuminuria to classify participants with CKD stages 1-5 according to the low, intermediate, and high/very high-risk groups suggested by KDIGO (Kidney Disease: Improving Global Outcomes). Cox proportional hazards model was applied to evaluate the associations of CKD with incident VTE. In addition, we used externally validated polygenic risk score (PRS) for VTE to evaluate whether the genetic predisposition modified the associations of interest. Results During median follow-up of 12.7 years, 11,372 participants developed VTE. As compared with low KDIGO risk category, covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for future VTE risk with intermediate and high/very high KDIGO risk categories at baseline were 1.278 (1.191-1.372) and 1.892 (1.658-2.159), respectively. Participants at high/very high risk of CKD prognosis and in the highest tertile of PRS had the highest risk of developing VTE (HR, 4.397; 95% CI, 3.639-5.313), and this group had shown the most conspicuous additive interactions between CKD and the genetic predisposition, which responsible for 1.389-fold relative excess risk and accounted for 31.6% of incident VTE. Also, when either eGFR or urine albumin-creatinine ratio (ACR) was treated as the exposure, similar associations and supra-additive interactions were yielded. Conclusion CKD is associated with future VTE, especially in those with high genetic risk.