Yazdani Babak, Delgado Graciela E, Berg Anders H, Wanner Christoph, Krämer Bernhard K, März Winfried, Kleber Marcus E, Drechsler Christiane
Fifth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology, Pneumology), University Medical Center Mannheim UMM, Faculty of Medicine of the University of Heidelberg, Mannheim, Germany.
European Center for Angioscience, Faculty of Medicine of the University of Heidelberg, Mannheim, Germany.
Clin Chem. 2025 May 2;71(5):587-598. doi: 10.1093/clinchem/hvaf021.
Urea is elevated in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and promotes the carbamylation of proteins, including human albumin, on multiple lysine side chains. Higher proportions of carbamylated albumin (C-Alb) have been associated with increased mortality risk in patients with ESRD. Whether C-Alb predicts mortality in patients with no or mild impairment of kidney function is unknown.
We measured C-Alb in 3197 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who had been referred to coronary angiography and followed-up for 10 years. Association of baseline C-Alb with all-cause and cause-specific mortality was investigated using Cox proportional hazards regression.
Higher quartiles of C-Alb were associated with a significantly increased risk of death from any cause, with hazard ratios (HRs, 95%CI) of 1.53 (1.26-1.85) and 2.52 (2.11-3.01) in the third and fourth quartiles, respectively. After adjustment for cardiovascular (CV) risk factors, including estimate glomerular filtration rate (eGFR), the association with mortality was attenuated with a HR of 1.25 (1.02-1.53) for the fourth quartile as compared to the first quartile. We observed the strongest association with death due to congestive heart failure (HF) with a HR of 7.19 (4.57-11.3) and 3.99 (2.40-6.63) per 1-unit increase of log-transformed C-Alb in unadjusted and multivariate adjusted analyses, respectively.
We observed a strong association of C-Alb with CV risk in patients with no or mild CKD. This association was independent of traditional CV risk factors including eGFR and particularly strong regarding death due to congestive HF.
慢性肾脏病(CKD)和终末期肾病(ESRD)患者体内尿素水平升高,可促使包括人白蛋白在内的多种蛋白质的赖氨酸侧链发生氨甲酰化。氨甲酰化白蛋白(C - Alb)比例较高与ESRD患者死亡风险增加有关。C - Alb能否预测肾功能未受损或轻度受损患者的死亡率尚不清楚。
我们在路德维希港风险与心血管健康(LURIC)研究的3197名参与者中测量了C - Alb,这些参与者均接受了冠状动脉造影检查并随访10年。使用Cox比例风险回归研究基线C - Alb与全因死亡率及特定病因死亡率之间的关联。
C - Alb较高四分位数与任何原因导致的死亡风险显著增加相关,第三和第四四分位数的风险比(HRs,95%CI)分别为1.53(1.26 - 1.85)和2.52(2.11 - 3.01)。在调整包括估计肾小球滤过率(eGFR)在内的心血管(CV)危险因素后,与死亡率的关联减弱,第四四分位数与第一四分位数相比,HR为1.25(1.02 - 1.53)。我们观察到与充血性心力衰竭(HF)导致的死亡关联最强,在未调整和多变量调整分析中,每增加1个对数转换后的C - Alb单位,HR分别为7.19(4.57 - 11.3)和3.99(2.40 - 6.63)。
我们观察到在无或轻度CKD患者中,C - Alb与CV风险之间存在强烈关联。这种关联独立于包括eGFR在内的传统CV危险因素,尤其在因充血性HF导致的死亡方面表现强烈。