Effect of Mixed On-line Hemodiafiltration on Circulating Markers of Inflammation and Vascular Dysfunction

This is an open label placebo-controlled randomized clinical trial to assess the effect of mixed OL-HDF (mOL-HDF) on different circulating mediators of vascular dysfunction. Inclusion criteria: age \> 18 yrs, hemodialytic treatment from at least 6 months (3 times for week), blood flow rate (Qb) ≥ 250 ml/min using arterovenous fistula (AVF) or permanent central venous catheter (CVC), blood creatinine clearance \<5 ml/min, urine output\<500 ml/die. Exclusion criteria: neoplastic diseases, chronic autoimmune diseases, lack of consent, solid organ or bone marrow transplantation. Safety Assessment: the use of mOL-HDF has been approved by the European Medicines Agency as routine hemodepurative technique for end stage renal disease patients. Patients were evaluated for adverse reaction at each dialysis section; investigators recorded intra and extra-dialytic adverse events. Study Treatment, Dosage, and Route of Administration: Enrolled patients have been randomized in 2 groups: 15 patients continued high flux bicarbonate hemodialysis (BHD), whereas 15 patients switched to mixed on-line hemodiafiltration (mOL-HDF using FX 1000 CorDiax, Fresenius Medical Care, Bad Homburg, Germany) for 9 months. Efficacy Assessments: Main outcome variable: changes in RNA content of circulating exosome/microvesicles (at 9 months) Secondary outcomes: changes in circulating inflammatory markers (C-Reactive Protein, Neutrophil Gelatinase Associated Lipocalin, Interleukin-6, Ferritin) at 3-6 and 9 months. changes in RNA content of circulating microvesicles (at 3 and 6 months) Study Duration: 9 months Statistical Methods: Data have been analyzed according to an intention-to-treat approach. Statistical analysis was performed using the unpaired Student t -test, ANOVA, or Kruskal-Wallis test when appropriate. A two-sided value of p=0.05 was considered significant.