Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Medicine, New York University, New York, NY, USA.
BMC Nephrol. 2024 May 30;25(1):185. doi: 10.1186/s12882-024-03619-6.
Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies.
Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker.
Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics.
C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.
蛋白质碳化，一种主要由尿素驱动的翻译后蛋白质修饰，与 CKD 患者的不良临床结局独立相关。用于量化碳化负担的生物标志物主要包括碳化白蛋白（C-Alb）和同型瓜氨酸（HCit，碳化赖氨酸）。在这项研究中，我们旨在比较这两种标志物的预后效用，以便于比较单独使用任何一种标志物的现有研究，并为未来的碳化研究提供信息。
在前瞻性慢性肾功能不全队列（CRIC）研究中，从 1632 名 CKD 2-4 期患者的同一时间点检测血清 C-Alb 和游离 HCit 水平。使用调整后的 Cox 比例风险模型评估每种标志物的死亡（主要）和终末期肾病（ESKD）结局的风险。使用 C 统计量、净重新分类改善和综合判别改善来比较每种标志物的预后价值。
参与者的人口统计学特征包括平均（SD）年龄 59（11）岁；702 名（43%）女性；700 名（43%）白人。C-Alb 和 HCit 水平呈正相关（Pearson 相关系数 0.64）。较高的 C-Alb 和 HCit 水平显示出相似的死亡风险增加（例如，第 4 碳化四分位与第 1 碳化四分位相比，死亡的调整后危险比[HR]为 1.90（95%置信区间[CI]为 1.35-2.66）对于 C-Alb，而 1.89[1.27-2.81]对于 HCit；在连续范围内，使用 C-Alb 的死亡的调整 HR 为每标准偏差增加 1.24[1.11 至 1.39]，使用 HCit 的为 1.27[1.10 至 1.46]）。两种生物标志物在 ESKD 方面的 HR 也相似。当将每种碳化生物标志物添加到基础模型中时，C 统计量相似（例如，对于死亡率模型，C 统计量为 0.725[0.707-0.743]，C-Alb 为 0.725[0.707-0.743]，而基础模型为 0.723）。在净重新分类改善和综合判别改善指标上也观察到相似性。
C-Alb 和 HCit 在多项预后评估中表现相似。这些标志物在 CKD 流行病学研究中似乎可以直接比较。
