Department of Medicine, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Analytica Now, Brookline, Massachusetts.
J Am Soc Nephrol. 2023 May 1;34(5):876-885. doi: 10.1681/ASN.0000000000000078. Epub 2023 Jan 21.
Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted.
Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD.
To test associations between protein carbamylation and the primary outcome of progression to ESKD, we measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2-4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study.
The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m 2 , and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8-10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb ≤5.80 mmol/mol), those in quartile 4 (C-Alb >10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR.
Having a higher level of protein carbamylation as measured by circulating C-Alb is an independent risk factor for ESKD in individuals with CKD stages 2-4.
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蛋白碳化作用，一种非酶促的蛋白质翻译后修饰，部分由血液尿素水平升高驱动，与透析治疗的终末期肾病（ESKD）患者的死亡率和不良结局相关。然而，在更早阶段的慢性肾脏病（CKD）患者的更大人群中，关于碳化作用与临床结局的关系知之甚少。在这项对 3111 名 CKD 2-4 期患者的前瞻性观察性队列研究中，更高水平的碳化白蛋白（蛋白碳化作用负担的标志物）与发展为 ESKD 和其他重大不良临床结局的风险增加相关。这些发现表明蛋白碳化作用是 CKD 进展的一个独立危险因素。它们表明，有必要进一步研究预防或减少碳化作用的治疗干预措施。
蛋白碳化作用，一种部分由血液尿素水平升高驱动的蛋白质翻译后修饰，与 ESKD 的不良结局相关。然而，在更早阶段的 CKD 患者的更大人群中，关于蛋白碳化作用与临床结局的关系知之甚少。
为了测试蛋白碳化作用与进展为 ESKD 的主要结局之间的关系，我们在前瞻性观察性慢性肾功能不全队列研究中测量了 3111 名 CKD 2-4 期患者的基线血清碳化白蛋白（C-Alb）。
研究参与者的平均年龄为 59 岁（标准差 10.8）；1358 名（43.7%）为女性，1334 名（42.9%）为白人。在评估 C-Alb 时的平均 eGFR 为 41.8（16.4）ml/min/1.73m2，中位数 C-Alb 值为 7.8mmol/mol（四分位距，5.8-10.7）。在平均 7.9（4.1）年的随访期间，981 名（31.5%）患者发展为 ESKD。在多变量调整的 Cox 模型中，较高的 C-Alb（连续或四分位数）与 ESKD 风险增加独立相关。例如，与四分位 1（C-Alb≤5.80mmol/mol）相比，四分位 4（C-Alb>10.71mmol/mol）的患者发生 ESKD 的风险更高（调整后的危险比，2.29；95%置信区间，1.75 至 2.99），并且从四分位 1 到四分位 4，每 1000 名患者年的 ESKD 发生率从 15.7 增加到 88.5。当将死亡视为竞争事件，以及使用不同的 eGFR 评估时，结果仍然具有显著性。
在 CKD 2-4 期患者中，循环 C-Alb 水平升高与蛋白碳化作用升高是 ESKD 的一个独立危险因素。
