Is oxidative stress an issue in peritoneal dialysis?

Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4. Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS. Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level. Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.

Chronic kidney disease (CKD) patients are among the groups at the highest risk for cardiovascular disease and significantly shortened remaining lifespan. CKD enhances oxidative stress in the organism with ensuing cardiovascular damage. Oxidative stress in uremia is the consequence of higher reactive oxygen species (ROS) production, whereas attenuated clearance of pro-oxidant substances and impaired antioxidant defenses play a complementary role. The pathophysiological mechanism underlying the increased ROS production in CKD is at least partly mediated by upregulation of the intrarenal angiotensin system. Enhanced oxidative stress in the setting of the uremic milieu promotes enzymatic modification of circulating lipids and lipoproteins, protein carbamylation, endothelial dysfunction via disruption of nitric oxide (NO) pathways, and activation of inflammation, thus accelerating atherosclerosis. Left ventricular hypertrophy (LVH) and heart failure are hallmarks of CKD. NADPH oxidase activation, xanthine oxidase, mitochondrial dysfunction, and NO-ROS are the main oxidative pathways leading to LVH and the cardiorenal syndrome. Finally, a subset of antioxidant enzymes, the paraoxonases (PON), deserves special attention due to abundant clinical evidence accumulated regarding reduced serum PON1 activity in CKD as a contributor to the increased burden of cardiovascular disease. Future, meticulously designed studies are needed to assess the effects of antioxidant therapy on patients with CKD.