Oxidative stress, inflammation, and peritoneal dialysis: A molecular biology approach

Abstract

The key role of oxidative stress (OxSt) and inflammation for the induction of cardiovascular disease, the leading cause of excess morbidity/mortality in chronic kidney disease and dialysis patients, is known and both the activations of NADPH oxidase and RhoA/Rho kinase (ROCK) pathway are pivotal for their effects. While specific hemodialysis procedures, such as hemodiafiltration with on-line reinfusion of ultrafiltrate and/or the use of vitamin E-coated dialyzers, are beneficial for OxSt and inflammation, studies in peritoneal dialysis (PD) are instead scarce and results seem not favorable. In nine patients under PD OxSt in terms of mononuclear cell protein level of p22^phox (Western blot), subunit of NADPH oxidase, essential for the generation of OxSt, and MYPT-1 phosphorylation state (Western blot), a marker of ROCK activity, have been measured at the beginning and after 3 and 6 months of PD. Blood levels of interleukin 6 (IL-6), ferritin, and albumin have been considered for evaluating the inflammatory state. p22^phox protein expression, MYPT-1-phosphorylation, and ferritin level were increased both at baseline vs healthy subjects (P = .02, P < .0001, P = .004, respectively) and vs baseline after 3 and 6 months of peritoneal dialysis (P = .007, P < .001, P = .004, respectively). Albumin was lower after 6 months of PD (P = .0014). IL-6 was increased at baseline vs reference values and remained unchanged at 3 and 6 months. OxSt and inflammation increase during PD confirming via molecular biology approach a report at biochemical level. To improve OxSt state in PD, a multitarget approach is necessary. It might include the use of more physiologic pH, low glucose degradation products, low lactate and iso-osmolar PD solutions, patients' strict glycemic control, optimal volume management, and antioxidant administration, such as N-acetylcysteine.

Keywords: NADPH oxidase; Rho kinase; cardiovascular risk; oxidative stress; peritoneal dialysis.