Trottier Caitlin, Perl Jeffrey, Freeman Megan, Thadhani Ravi, Berg Anders, Kalim Sahir
Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Division of Nephrology, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Perit Dial Int. 2018 Mar-Apr;38(2):149-152. doi: 10.3747/pdi.2017.00176.
Protein carbamylation is a post-translational urea-driven protein modification associated with mortality. Free amino acids (AAs) competitively inhibit protein carbamylation and parenteral AA therapy reduces carbamylation in hemodialysis (HD) patients. Peritoneal dialysis (PD) yields differences in urea clearance and AA balance compared with HD, but the influence of PD and intraperitoneal AA solutions on carbamylation is unclear. Thus, we first measured carbamylated albumin (C-Alb; a marker of carbamylation load) in 100 diabetic HD patients frequency-matched by age, sex, and race to 98 diabetic PD subjects from the IMPENDIA trial, which originally compared the metabolic effects of low-glucose PD solutions (incorporating icodextrin and AAs) to a control group (dextrose-only solutions). We then determined the effects of the AA-enriched PD solutions by measuring the 6-month change in C-Alb within the IMPENDIA cohort by treatment allocation (48 treated vs 50 controls). Peritoneal dialysis patients, when compared with HD patients, had higher baseline urea and higher C-Alb. Among IMPENDIA participants, there was no difference in C-Alb change in either arm, but treated subjects showed a trend towards increased carbamylation. Treated subjects also demonstrated an increase in urea, possibly explaining the carbamylation trend. In summary, carbamylation levels in PD patients appeared higher than in matched HD patients. A regimen of AA and low-glucose PD solutions did not reduce C-Alb in IMPENDIA subjects.
蛋白质氨甲酰化是一种与死亡率相关的翻译后尿素驱动的蛋白质修饰。游离氨基酸（AA）竞争性抑制蛋白质氨甲酰化，肠外给予氨基酸疗法可降低血液透析（HD）患者的氨甲酰化水平。与HD相比，腹膜透析（PD）在尿素清除率和氨基酸平衡方面存在差异，但PD和腹腔内氨基酸溶液对氨甲酰化的影响尚不清楚。因此，我们首先在100例糖尿病HD患者中测量了氨甲酰化白蛋白（C-Alb；氨甲酰化负荷的标志物），这些患者在年龄、性别和种族上与来自IMPENDIA试验的98例糖尿病PD受试者进行了频率匹配，该试验最初比较了低葡萄糖PD溶液（包含艾考糊精和氨基酸）与对照组（仅含葡萄糖的溶液）的代谢效应。然后，我们通过按治疗分配（48例治疗组与50例对照组）测量IMPENDIA队列中C-Alb的6个月变化，来确定富含氨基酸的PD溶液的效果。与HD患者相比，腹膜透析患者的基线尿素水平和C-Alb水平更高。在IMPENDIA参与者中，两组的C-Alb变化没有差异，但治疗组受试者显示出氨甲酰化增加的趋势。治疗组受试者的尿素也有所增加，这可能解释了氨甲酰化趋势。总之，PD患者的氨甲酰化水平似乎高于匹配的HD患者。在IMPENDIA受试者中，氨基酸和低葡萄糖PD溶液方案并未降低C-Alb水平。
