Oxidative stress reduction by icodextrin-based glucose-free solutions in peritoneal dialysis: Support for new promising approaches

BackgroundOxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions.Patients and MethodsThis study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation.Resultsp22phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 +/- 0.18 d.u. vs. 1.50 +/- 0.19, p = 0.049; 0.89 +/- 0.03 vs. 0.98 +/- 0.03, p = 0.004; 4.20 +/- 0.18 nmol/mL vs. 4.84 +/- 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 +/- 0.06 vs. 0.99 +/- 0.04, p = 0.043), while p22phox protein expression was reduced only at 6 months versus baseline (1.03 +/- 0.05 vs. 1.68 +/- 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 +/- 0.24 nmol/mL vs. 4.68 +/- 0,32, p = 0.024) and also versus 3 months (4.03 +/- 0.24 vs. 4.35 +/- 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance.ConclusionsThe reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation. Oxidative stress (OxSt) and inflammation, known CV and mortality risk factors, are common in CKD. In peritoneal dialysis (PD) OxSt even increases due to the glucose-based solutions. Studies in PD on the impact of more biocompatible solutions such as icodextrin-based solutions on OxSt are scanty. The icodextrin-based PD solutions induced reduction of OxSt-related proteins supporting the rationale of replacing the currently used glucose-based fluids.image