Background and Objective

In end-stage kidney disease, high urea levels promote the carbamylation of lysine side chains on a variety of proteins, including albumin. Albumin carbamylation has been identified as a risk factor for mortality and sevelamer led to a decrease in urea levels in dialysis patients. In the present secondary analysis of the NICOREN trial, we investigated the putative impacts of sevelamer and nicotinamide on albumin carbamylation, and the potential correlation between carbamylation and vascular calcifications.

Methods

All possible carbamylation of circulating albumin were screened for with high-resolution liquid chromatography-tandem mass spectrometry. Levels of three carbamylated peptides were then measured as a guide to the extent of albumin carbamylation. Carbamylation was measured at baseline in 55 patients included in the NICOREN trial and 29 patients at 24 weeks of treatment. Calcifications on plain radiographs were quantified as the Kauppila score and the Adragao score.

Results

Baseline albumin carbamylation was present at three different sites in subjects with end-stage kidney disease. At baseline, we observed only a correlation between urea and the KQTA carbamylation site in these patients. Albumin carbamylation levels did not decrease after 24 weeks of treatment with either sevelamer or nicotinamide. Furthermore, the proportion of carbamylated serum albumin was not correlated with vascular calcification scores in this population.

Conclusions

Our results confirmed the presence of carbamylated albumin in patients with end-stage kidney disease and demonstrated the presence of carbamylation beyond the LRVP residues. The results also demonstrated the lack of impact of sevelamer or nicotinamide on albumin carbamylation levels. Therapeutic strategies to lower carbamylation load should probably be focused on direct anti-carbamylation processes and/or potentially anti-inflammatory therapies.

中文翻译：

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司维拉姆和烟酰胺对终末期肾病患者白蛋白氨基甲酰化的影响

背景与目的

在终末期肾病中，高尿素水平会促进包括白蛋白在内的多种蛋白质上赖氨酸侧链的氨甲酰化。白蛋白氨基甲酰化已被确定为死亡率的危险因素，司维拉姆导致透析患者尿素水平降低。在目前对 NICOREN 试验的二次分析中，我们调查了司维拉姆和烟酰胺对白蛋白氨基甲酰化的推定影响，以及氨基甲酰化与血管钙化之间的潜在相关性。

方法

使用高分辨率液相色谱-串联质谱法筛选了所有可能的循环白蛋白氨甲酰化。然后测量三种氨基甲酰化肽的水平作为白蛋白氨基甲酰化程度的指导。包括在 NICOREN 试验中的 55 名患者和 29 名患者在治疗 24 周时在基线时测量了氨基甲酰化。平片上的钙化被量化为 Kauppila 评分和 Adragao 评分。

结果

基线白蛋白氨基甲酰化存在于终末期肾病受试者的三个不同部位。在基线时，我们仅在这些患者中观察到尿素和 KQTA 氨甲酰化位点之间存在相关性。用司维拉姆或烟酰胺治疗 24 周后，白蛋白氨基甲酰化水平没有降低。此外，氨甲酰化血清白蛋白的比例与该人群中的血管钙化评分无关。

结论

我们的结果证实了终末期肾病患者中存在氨甲酰化白蛋白，并证明存在超出 LRVP 残基的氨甲酰化。结果还证明司维拉姆或烟酰胺对白蛋白氨基甲酰化水平没有影响。降低氨基甲酰化负荷的治疗策略可能应该集中在直接的抗氨基甲酰化过程和/或潜在的抗炎治疗上。