Kalim Sahir, Ortiz Guillermo, Trottier Caitlin A, Deferio Joseph J, Karumanchi S Ananth, Thadhani Ravi I, Berg Anders H
Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
J Ren Nutr. 2015 Jul;25(4):388-92. doi: 10.1053/j.jrn.2015.01.019. Epub 2015 Mar 5.
Protein carbamylation is a urea-driven post-translational protein modification associated with mortality in dialysis patients. Free amino acids (AAs) are competitive inhibitors of protein carbamylation and animal studies suggest increasing AA concentrations reduces carbamylation burden. We hypothesized that AA therapy in maintenance hemodialysis patients would reduce carbamylation, carrying the potential to improve clinical outcomes.
Prospective pilot clinical trial (NCT1612429).
The study was conducted from March 2013 to March 2014 in outpatient dialysis facilities in the Boston metropolitan area.
We enrolled 23 consecutively consenting hemodialysis subjects, infusing the first 12 individuals with 250 cc of AAs 3 times per week postdialysis over 8 weeks. The remaining 11 subjects served as controls.
Change in carbamylated albumin (C-Alb), a measure of total body carbamylation burden, between baseline and 8 weeks was the primary outcome.
The treated and control groups had similar clinical characteristics and similar baseline C-Alb levels (mean ± SE 9.5 ± 2.4 and 9.3 ± 1.3 mmol/mol, respectively; P = .61). The treated arm showed a significant reduction in C-Alb compared with controls at 4 weeks (8.4% reduction in the treated arm vs. 4.3% increase in controls; P = .03) and the effect was greater by 8 weeks (15% reduction in the treated vs. 1% decrease in controls; P = .01).
In this pilot study, AA therapy appeared safe and effective at reducing C-Alb levels in hemodialysis patients compared with no treatment. The impact of reduced protein carbamylation on clinical outcomes should be further investigated.
蛋白质氨甲酰化是一种由尿素驱动的翻译后蛋白质修饰，与透析患者的死亡率相关。游离氨基酸（AA）是蛋白质氨甲酰化的竞争性抑制剂，动物研究表明增加AA浓度可减轻氨甲酰化负担。我们假设，维持性血液透析患者接受AA治疗可减少氨甲酰化，有可能改善临床结局。
前瞻性试点临床试验（NCT1612429）。
该研究于2013年3月至2014年3月在波士顿大都会区的门诊透析设施中进行。
我们连续招募了23名同意参与的血液透析受试者，在透析后每周3次给前12名个体输注250 cc的AA，持续8周。其余11名受试者作为对照。
基线和8周时氨甲酰化白蛋白（C-Alb）的变化，这是全身氨甲酰化负担的一项指标，为主要结局。
治疗组和对照组具有相似的临床特征和相似的基线C-Alb水平（分别为均值±标准误9.5±2.4和9.3±1.3 mmol/mol；P = 0.61）。在4周时，治疗组的C-Alb与对照组相比显著降低（治疗组降低8.4%，对照组增加4.3%；P = 0.03），到8周时效果更明显（治疗组降低15%，对照组降低1%；P = 0.01）。
在这项试点研究中，与未治疗相比，AA治疗在降低血液透析患者的C-Alb水平方面似乎安全有效。蛋白质氨甲酰化减少对临床结局的影响应进一步研究。
