#2881 Glucose free-based solutions reduce oxidative stress in peritoneal dialysis: support for a new promising approach

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Abstract Background and Aims Oxidative stress (OxSt) and inflammation are common in CKD which are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions. This study evaluated in PD patients the effect of 3 and 6 months treatment with icodextrin-based glucose-free solutions on OxSt and inflammation. Method In 15 PD patients using a molecular biology approach, p22phox protein expression (Western blot), subunit of NADPH oxidase, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway activity, deeply involved in OxSt generation (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay), marker of lipid peroxidation, have been evaluated. High-sensitive C Reactive Protein (hsCRP) (immunoturbidimetric assay) and interleukin (IL)-6 (chemiluminescence assay), have been used as marker of inflammation. Results p22phox protein expression, MYPT-1 phosphorylation, and MDA level were reduced after 3 months from the start of icodextrin based solutions (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 from baseline (1.03 ± 0.05 vs 1.68 ± 0.22, p = 0.021). In this subgroup MDA blood level was reduced at 6 months from baseline (4.03 ± 0.24 nmol/mL vs 4.68 ± 0.32, p = 0.024) and was also significantly reduced vs 3 months (4.03 ± 0.24 vs 4.35 ± 0.21, p = 0.008). IL-6 level, although reduced compared to baseline, did not reach statistical significance both at 3 and 6 months, while hsPCR was unchanged. Conclusion The icodextrin-based PD solutions mediated reduction of OxSt related proteins and inflammation we have provided, although obtained in a small cohort of patients and for a limited time duration, strongly support the rationale of using in PD osmo-metabolic agents-based solutions replacing the currently used glucose-based fluids. The results of ongoing studies with these agents in PD patients will provide definitive proofs to better preserve peritoneal membrane integrity and residual renal function but also to reduce CV risk factors such as OxSt and inflammation.