Quantitation of Markers of Protein Damage by Glycation, Oxidation, and Nitration in Peritoneal Dialysis

Abstract

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.

Plasma myeloperoxidase, NT‐proBNP, and troponin‐I in patients on CAPD compared with those on regular hemodialysis

“…Oxidative stress during peritoneal dialysis has been established in many studies. 22,23 Generation of oxidative stress products such as reactive oxygen species (ROS) and MPO by conventional peritoneal dialysis solutions has been claimed responsible for progressive membrane dysfunction 24 and the level of different ROS has been used to check for the level of oxidative stress in these patients. Numerous studies have reported that the elevated levels of oxidative stress and inflammation in dialysis patients are associated with arterial stiffness and in turn with the development of CVD.…”

Probing Protein Glycation by Chromatography and Mass Spectrometry: Analysis of Glycation Adducts

“…Generally, analysis at the level of individual amino acids (either free, or obtained by exhaustive hydrolysis of proteins) is the most straightforward and direct way to characterize the structures and quantities of glycation products, occurring in artificial and natural systems [ 86 ]. Therefore, the employed analytical strategies most commonly rely on amino acid analysis protocols, and provide a direct access to absolute quantities of individual glycation adduct classes (as well as unmodified amino acids) in biological samples of various origin and complexity [ 65 ].…”

Antioxidant capacity: Which capacity and how to assess it?

“…Reliable biomarkers are required for this purpose and many biomarkers have been applied to measure the level of oxidative stress in vivo [1,7,32]. Various oxidation products of lipids [33][34][35], proteins [36,37], and DNA [38] have been used as oxidative stress biomarkers as summarized in Table 2. Isoprostanes formed by the free radical-mediated oxidation of arachidonates are accepted to be most reliable biomarker of oxidative stress in vivo.…”