Association between genetic risk and renal function for developing venous thromboembolism

Abstract

Background Kidney disease is regarded as a risk factor for venous thromboembolism (VTE), but the association between renal function and the risk of VTE remains unclear. Methods This study was conducted using a sample of 358,723 participants from the UK Biobank. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of VTE incidence associated with renal function levels were estimated using the Cox proportional hazards model based on the baseline exposure measurements. Additionally, the relationship between renal function and cumulative risk of VTE was visualized using Kaplan-Meier curves as well as restricted cubic spline (RCS). Furthermore, this study investigated the combined effects and interactions between renal function biomarkers and genetic predisposition in relation to the risk of VTE onset. Results Biomarkers of renal function in the highest quartile levels (lowest quartile levels for eGFR) were associated with an elevated risk of VTE onset, with HR (95% CI) of 1.21 (1.12–1.30) for urine creatinine, 1.23 (1.13–1.34) for serum creatinine, 1.12 (1.04–1.2) for urea, 1.15 (1.06–1.26) for urate, 1.59 (1.46–1.73) for cystatin C, 1.28 (1.14–1.43) for urine microalbumin, and 1.47 (1.36–1.60) for eGFR. For the joint associations, participants with both high levels of renal function biomarkers (low levels of eGFR) and high genetic risk had the highest risk of developing VTE, with 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 eGFR. Conclusions Elevated levels of urine creatinine, serum creatinine, urea, urate, cystatin C, urine microalbumin, and reduced eGFR would increase the risk of VTE, and there were positive additive effect of renal function and genetic susceptibility on the risk of VTE.