Advanced glycosylation end products as metabolic predictors of systemic pro-inflammatory and prooxidant status in patients with end-stage renal disease.

Controlling systemic proinflammatory and prooxidant effectors is essential for mitigating cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, monitoring these processes is still challenging due to the high uncertainty about their determinants and predictors. Thus, we investigated the relationship between advanced glycosylation end products (AGE), proinflammatory and prooxidant effectors in ESRD patients undergoing hemodialysis (HD). In addition to nutritional profile and dialysis efficiency, AGE, cytokines, chemokines, C-reactive protein (CRP), total (TAC) and non-protein (npAC) antioxidant capacity, lipid and protein oxidation were analyzed in blood samples from 43 HD patients. AGE, CRP, cytokines, chemokines, protein carbonyl (PCn), and malondialdehyde (MDA) were upregulated, while TAC and npAC were down-regulated in HD patients compared to heath subjects. Dialysis efficiency, TAC and npAC were reduced, while leucocytes counting, pre- and post-HD urea, TNF, IL-6, IL-10, CCL-2, MIP-1ß, PCn, and MDA were increased in patients with higher AGE accumulation compared to those with lower AGE levels. Serum levels of CRP, protein carbonyl, malondialdehyde, and all cytokines and chemokines analyzed were correlated with AGE circulating levels for patients with higher AGE accumulation. AGE was inversely correlated with IL-10, TAC and npAC in patients with higher AGE accumulation. AGE exhibited predictive value (determination coefficient) to explain CRP, cytokines, chemokines, PCN, MDA, TAC and npAC variability in patients with higher AGE levels. Taken together, our findings provide evidence that AGE accumulation is associated with important proinflammatory and prooxidant effectors in patients with ESRD undergoing hemodialysis. Thus, AGE monitoring may be relevant to predict systemic inflammatory stress and the balance between oxidant and antioxidant status in these patients.

Cytokines and chemokines systemic levels are related to dialysis adequacy and creatinine clearance in patients with end-stage renal disease undergoing hemodialysis.

Although the clearance of low-molecular weight toxins is modulated by dialysis dose, the relationship between dialysis adequacy and middle systemic inflammatory mediators is often overlooked. Thus, the relationship between dialysis adequacy, pro- and anti-inflammatory cytokines and chemokines in hemodialysis (HD) patients was investigated. Forty-eight HD patients (19 women and 25 men) were investigated. Age, body mass index, time in HD, nutritional status, Kt/V and blood biochemical parameters was similar in patients of both sexes (P > 0.05). Thus, patients were stratified by dialysis adequacy measured by Kt/V method (adequate Kt/V ≥ 1.2). Post-HD urea, creatinine, cytokines (IFN-γ, IL-4 and IL-10) and chemokines (CCL-2, CCL-5, CXCL-8 and CXCL-10) were higher in patients with Kt/V < 1.2 (P < 0.05). Kt/V exhibited significant correlation with CXCL-10/IP-10 serum levels. Positive correlation between creatinine with IFN-γ, CCL-2/MCP-1, and CXCL-10/IP-10, and negative correlation with IL-10 was identified in patients with Kt/V < 1.2 (P < 0.05). In patients with Kt/V ≥ 1.2, only IL-10 was positively and CXCL-10/IP-10 negatively correlated with creatinine levels (P < 0.05). Kt/V and creatinine levels exhibited variable predictive value (Kt/V = 27% to 37%, creatinine = 29% to 47%) to explain cytokines and chemokines circulating levels in patients with adequate and inadequate dialysis dose. Taken together, our findings provide evidence that in addition to modulating uremic toxins levels, such as urea and creatinine, dialysis dose is associated with circulating levels of inflammatory mediators. Thus, low Kt/V results and creatinine accumulation are potential indicators of the systemic inflammatory stress determined by up-regulation of proinflammatory cytokines and chemokines, and downregulation of anti-inflammatory cytokines.

Potential Role of Nutrient Intake and Malnutrition as Predictors of Uremic Oxidative Toxicity in Patients with End-Stage Renal Disease.

Oxidative stress is an important risk factor for cardiovascular disease and death in hemodialysis (HD) patients. However, whether biochemical and nutritional markers might be useful to stratify HD patients according to the risk of oxidative damage remains unclear. We investigated whether low-cost and easily available parameters such as the profile of nutrients intake, nutritional status, and antioxidant defenses can predict lipid and protein oxidation in HD patients. Forty-nine HD patients (women = 20, men = 29), ranging from 18 to 65 years of age (73.5%) were submitted to biochemical and nutritional analysis. At least 93.9% of HD patients had malnutrition. A patient's stratification according to nutritional risk was highly coherent with anthropometric parameters and nutrients intake, which were complementarily used as markers of malnutrition. Nutritional stratification was unable to reveal differences in the oxidative status. On the other hand, carbohydrate and zinc intake, serum zinc (Zn), glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC), and nonprotein antioxidants (npAC) in serum were predictive markers of lipid (R 2 = 0.588, P < 0.001) and protein (R 2 = 0.581, P < 0.001) oxidation. Interestingly, GPx activity, TAC, and npAC exhibited good (>80% < 90%) or excellent (>90%) accuracy to estimate lipid oxidation (P ≤ 0.01). Regarding the prediction of protein oxidation, GPx activity and TAC presented regular accuracy (>70% < 80%), and Zn serum levels exhibited good sensitivity (P ≤ 0.01). Herein, we provided evidence that clinical characteristics relevant to predict different levels of lipid and protein oxidation in HD patients can be easily obtained, during routine hospital visits by means of the combined analyses of biochemical and nutritional parameters.