Gan Zeyu, Guan Yunlong, Li Si, Kong Yifan, Deng Jun, Hao Xingjie
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.
School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology.
J Atheroscler Thromb. 2025 Jun 1;32(6):703-722. doi: 10.5551/jat.65328. Epub 2024 Nov 30.
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.
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.
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.
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.
肾功能降低对静脉血栓栓塞症（VTE）风险的影响仍存在争议。VTE与肾功能以及遗传易感性之间的关联，需要在大量人群中进一步阐明。
本研究纳入了英国生物银行中358,723名无肾衰竭的参与者。使用Cox比例风险模型估计基线时与肾功能相关的VTE发病风险的风险比（HRs）和95%置信区间（CIs）。此外，使用Kaplan-Meier曲线和受限立方样条（RCS）直观显示肾功能与VTE累积风险之间的关系。此外，本研究调查了肾功能与遗传易感性对VTE发病风险的联合效应和相互作用。
尿肌酐、血清肌酐、尿素、尿酸、胱抑素C和尿微量白蛋白处于最高四分位数水平以及估算肾小球滤过率（eGFR）处于最低四分位数水平的肾功能生物标志物与VTE发病风险升高相关。对于与遗传易感性的联合分析，肾功能生物标志物水平高（eGFR低）且遗传风险高的参与者发生VTE的风险最高，尿肌酐的HR（95%CI）为2.83（2.46 - 3.26），血清肌酐为2.72（2.37 - 3.13），尿素为2.49（2.18 - 2.84），尿酸为2.63（2.26 - 3.05），胱抑素C为3.52（3.01 - 4.13），尿微量白蛋白为2.90（2.33 - 3.60），eGFR为3.37（2.86 - 3.98）。
肾功能下降会增加VTE风险，遗传易感性对VTE风险有正向累加效应。这表明肾功能生物标志物可作为VTE的预测指标，尤其是在对VTE具有遗传易感性的人群中。
