Association between Genetic Risk and the Renal Function for Developing Venous Thromboembolism

Aims: The impact of a reduced renal function on the risk of venous thromboembolism (VTE) remains controversial. The association between VTE and the renal function, as well as genetic susceptibility, requires further clarification in a large population.

Methods: This study included 358,723 participants with non-renal failure from the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of VTE incidence associated with the renal function at baseline were estimated using the Cox proportional hazards model. In addition, the relationship between the renal function and cumulative risk of VTE was visualized using Kaplan-Meier curves and restricted cubic spline (RCS). Furthermore, this study investigated the combined effects and interactions between the renal function and genetic susceptibility on the risk of VTE onset.

Results: Renal function biomarkers in the highest quartile levels for urine creatinine, serum creatinine, urea, urate, cystatin C, and urine microalbumin and lowest quartile levels for the estimated glomerular filtration rate (eGFR) were associated with an elevated risk of VTE onset. For the joint analysis with genetic susceptibility, participants with both high levels of renal function biomarkers (a low eGFR) and high genetic risk had the highest risk of developing VTE, with an HR (95% CI) of 2.83 (2.46-3.26) for urine creatinine, 2.72 (2.37-3.13) for serum creatinine, 2.49 (2.18-2.84) for urea, and 2.63 (2.26-3.05) for urate, 3.52 (3.01-4.13) for cystatin C, 2.90 (2.33-3.60) for urine microalbumin, and 3.37 (2.86-3.98) for the eGFR.

Conclusions: A decreased renal function increases the risk of VTE and genetic susceptibility has a positive additive effect on VTE risk. This suggests that biomarkers of the renal function may be used as predictors of VTE, especially in populations with genetic susceptibility to VTE.