Rabbani Naila, Thornalley Paul J
Warwick Medical School, Clinical Sciences Research Institute, University of Warwick, University Hospital, Coventry, UK.
Perit Dial Int. 2009 Feb;29 Suppl 2:S51-6.
Proteolysis products of proteins damaged by glycation, oxidation, and nitration-glycated, oxidized, and nitrated amino acids (glycation, oxidation, and nitration free adducts)-are waste products normally excreted in urine and cleared in peritoneal dialysate. Glucose degradation products in peritoneal dialysis (PD) fluids may increase protein damage, giving rise to increased protein glycation, oxidation, and nitration adduct residues of proteins and increased flux of glycation, oxidation, and nitration free adducts. Increased protein damage has been linked to mortality in end-stage renal disease. Reliable quantitation of markers for adducts of protein glycation, oxidation, and nitration is required for mechanistic studies and for morbidity and mortality risk analysis in PD patients. We review the available analytical techniques for such quantitation. Stable isotopic dilution analysis with tandem mass spectrometry is the "gold standard." This method needs to be applied further in the study of PD and to validate other techniques so that the effect of PD on the metabolism and clearance of damaged proteins and related products can be quantified, and so that best-practice fluid management can be established to minimize cardiovascular risk.
由糖基化、氧化和硝化作用(糖基化、氧化和硝化游离加合物)导致蛋白质受损所产生的蛋白水解产物,是通常经尿液排出并在腹膜透析液中清除的废物。腹膜透析(PD)液中的葡萄糖降解产物可能会增加蛋白质损伤,导致蛋白质糖基化、氧化和硝化加合物残基增加,以及糖基化、氧化和硝化游离加合物通量增加。蛋白质损伤增加与终末期肾病的死亡率相关。在机制研究以及PD患者的发病率和死亡率风险分析中,需要可靠地定量蛋白质糖基化、氧化和硝化加合物的标志物。我们综述了用于此类定量分析的现有技术。串联质谱稳定同位素稀释分析是“金标准”。该方法需要在PD研究中进一步应用,并验证其他技术,以便能够量化PD对受损蛋白质及其相关产物代谢和清除的影响,从而建立最佳的液体管理方法,将心血管风险降至最低。