Hemodiafiltration Attenuates NETosis Compared With High-Flux Hemodialysis in End-Stage Kidney Disease Patients.

INTRODUCTION: Patients with chronic kidney disease (CKD) and diabetes mellitus face a heightened risk of cardiovascular complications and infections, potentially exacerbated by dysregulated NETosis. Given the superior survival rates observed with hemodiafiltration (HDF) over high-flux hemodialysis (HD; HFHD) and the documented NETosis dysregulation in HD and in patients with diabetes mellitus, this study aimed to investigate the impact of dialysis modality on NETosis activity in patients on HD, stratified by diabetes status. METHODS: A total of 20 patients on HD (10 with diabetes, 10 without diabetes) undergoing HDF treatment were recruited. Blood samples were collected before and after HDF. After transition to HFHD treatment, blood samples were taken again after 1 and 3 weeks of HDFD treatment. Neutrophils were isolated, stimulated with phorbol-12-myristate-13-acetate, and stained for the following NETosis markers: peptidyl arginine deiminase 4 (PAD4), neutrophil elastase (NE), myeloperoxidase (MPO), histone H3, and double-stranded DNA (dsDNA). Data were acquired using a flow cytometer. In addition, serum levels of citrullinated histone H3 (citH3), MPO, and NE were measured using enzyme-linked immunosorbent assay. RESULTS: Our results demonstrate a significant increase in NETosis activation and markers after HFHD treatment compared with HDF treatment. NETosis markers significantly increased in serum after 3 weeks of HFHD treatment. In addition, significantly lower NETosis markers were observed in patients with diabetes than in patients without diabetes. CONCLUSION: The increase in NETosis markers after 3 weeks of HFHD compared with HDF highlights the role of HDF in mitigating dysregulated NETosis. Further research is needed to explore differences in NETosis profiles across patient populations and assess their clinical implications based on dialysis modality.