PDF(Pubmed)
Abstract：
UNASSIGNED: Soluble urokinase plasminogen activation receptor (suPAR) is an immune-derived pathogenic factor for kidney and atherosclerotic disease. Whether the association between suPAR and cardiovascular (CV) outcomes is dependent on the severity of underlying kidney disease is unclear.
UNASSIGNED: We measured serum suPAR levels in 4994 participants (mean age 60 years; 60% men; 36% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) 49 ml/min per 1.73 m2, SD 18) of the German Chronic Kidney Disease (GCKD) cohort and examined its association with all-cause death, CV death, and major CV events (MACE) across the range of eGFR and urine albumin-to-creatinine ratio (UACR).
UNASSIGNED: The median suPAR level was 1771 pg/ml (interquartile range [IQR] 1447-2254 pg/ml). SuPAR levels were positively and independently correlated with age, eGFR, UACR, and parathyroid hormone levels. There were 573 deaths, including 190 CV deaths and 683 MACE events at a follow-up time of 6.5 years. In multivariable analyses, suPAR levels (log2) were associated with all-cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.21-1.53), CV death (HR 1.27, 95% CI 1.03-1.57), and MACE (HR 1.13, 95% CI 1.00-1.28), and were not found to differ according to diabetes mellitus status, baseline eGFR, UACR, or parathyroid hormone levels. In mediation analysis, suPAR\'s direct effect on all-cause death, CV death, and MACE accounted for 77%, 67%, and 60% of the total effect, respectively; whereas the effect mediated through eGFR accounted for 23%, 34%, and 40%, respectively.
UNASSIGNED: In a large cohort of individuals with chronic kidney disease (CKD), suPAR levels were associated with mortality and CV outcomes independently of indices of kidney function, consistent with its independent role in the pathogenesis of atherosclerosis.
UNASSIGNED: We measured serum suPAR levels in 4994 participants (mean age 60 years; 60% men; 36% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) 49 ml/min per 1.73 m2, SD 18) of the German Chronic Kidney Disease (GCKD) cohort and examined its association with all-cause death, CV death, and major CV events (MACE) across the range of eGFR and urine albumin-to-creatinine ratio (UACR).
UNASSIGNED: The median suPAR level was 1771 pg/ml (interquartile range [IQR] 1447-2254 pg/ml). SuPAR levels were positively and independently correlated with age, eGFR, UACR, and parathyroid hormone levels. There were 573 deaths, including 190 CV deaths and 683 MACE events at a follow-up time of 6.5 years. In multivariable analyses, suPAR levels (log2) were associated with all-cause death (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.21-1.53), CV death (HR 1.27, 95% CI 1.03-1.57), and MACE (HR 1.13, 95% CI 1.00-1.28), and were not found to differ according to diabetes mellitus status, baseline eGFR, UACR, or parathyroid hormone levels. In mediation analysis, suPAR\'s direct effect on all-cause death, CV death, and MACE accounted for 77%, 67%, and 60% of the total effect, respectively; whereas the effect mediated through eGFR accounted for 23%, 34%, and 40%, respectively.
UNASSIGNED: In a large cohort of individuals with chronic kidney disease (CKD), suPAR levels were associated with mortality and CV outcomes independently of indices of kidney function, consistent with its independent role in the pathogenesis of atherosclerosis.
摘要：
■可溶性尿激酶纤溶酶原激活受体（suPAR）是肾脏和动脉粥样硬化疾病的免疫衍生致病因子。suPAR与心血管（CV）结局之间的关联是否取决于潜在肾脏疾病的严重程度尚不清楚。
■我们测量了德国慢性肾脏病（GCKD）队列的4994名参与者（平均年龄60岁；60％男性；36％患有糖尿病；平均估计肾小球滤过率（eGFR）每1.73m249ml/min，SD18）的血清suPAR水平，并检查了其与全因死亡的关系，CV死亡,eGFR和尿白蛋白/肌酐比值（UACR）范围内的主要CV事件（MACE）。
■中值suPAR水平为1771pg/ml（四分位距[IQR]1447-2254pg/ml）。SuPAR水平与年龄呈正相关，独立相关，eGFR,UACR,甲状旁腺激素水平.有573人死亡,包括190例CV死亡和683例MACE事件，随访时间为6.5年。在多变量分析中，suPAR水平（log2）与全因死亡相关（风险比[HR]1.36，95%置信区间[CI]1.21-1.53），CV死亡（HR1.27，95%CI1.03-1.57），和MACE（HR1.13，95%CI1.00-1.28），并没有发现不同的糖尿病状态，基线eGFR，UACR,或甲状旁腺激素水平。在调解分析中，suPAR对全因死亡的直接影响，CV死亡,MACE占77%，67%,总效应的60%，分别；而通过eGFR介导的效应占23%，34%,40%,分别。
■在大量慢性肾病（CKD）患者中，suPAR水平与死亡率和心血管结局相关，独立于肾功能指标，其在动脉粥样硬化发病机制中的独立作用。
■我们测量了德国慢性肾脏病（GCKD）队列的4994名参与者（平均年龄60岁；60％男性；36％患有糖尿病；平均估计肾小球滤过率（eGFR）每1.73m249ml/min，SD18）的血清suPAR水平，并检查了其与全因死亡的关系，CV死亡,eGFR和尿白蛋白/肌酐比值（UACR）范围内的主要CV事件（MACE）。
■中值suPAR水平为1771pg/ml（四分位距[IQR]1447-2254pg/ml）。SuPAR水平与年龄呈正相关，独立相关，eGFR,UACR,甲状旁腺激素水平.有573人死亡,包括190例CV死亡和683例MACE事件，随访时间为6.5年。在多变量分析中，suPAR水平（log2）与全因死亡相关（风险比[HR]1.36，95%置信区间[CI]1.21-1.53），CV死亡（HR1.27，95%CI1.03-1.57），和MACE（HR1.13，95%CI1.00-1.28），并没有发现不同的糖尿病状态，基线eGFR，UACR,或甲状旁腺激素水平。在调解分析中，suPAR对全因死亡的直接影响，CV死亡,MACE占77%，67%,总效应的60%，分别；而通过eGFR介导的效应占23%，34%,40%,分别。
■在大量慢性肾病（CKD）患者中，suPAR水平与死亡率和心血管结局相关，独立于肾功能指标，其在动脉粥样硬化发病机制中的独立作用。
