Effect of an Online Hemodiafiltration (OL-HDF) Session in Children with Chronic Kidney Disease Stage 5 on Circulating Neutrophil Extracellular Traps (NETs)

Abstract Background Conventional Hemodialysis (HD) process can trigger inflammation and induce cytokines activation. Neutrophils extrude neutrophil extracellular traps (NETs) which are extracellular chromatin containing a variety of granular proteins that have been implicated in infection, as well as vascular inflammation and occlusion. Hence reducing HD induced neutrophil activation has the potential benefit of ameliorating both acute and chronic inflammatory conditions in CKD patients. Strategies to achieve this goal aim at having more biocompatible dialyzer membrane polymers and sterilization techniques and more efficient new dialysis modalities like online hemodiafiltration (OL-HDF). To our knowledge the effect of OL-HDF on neutrophil activation in children with chronic kidney disease stage 5 on dialysis (CKD-5d) has not been studied. Objective To assess the effect of a single OL-HDF session on the level of circulating NETs in children with CKD-5d. Methods This is a cross sectional study done at Pediatric Dialysis Unit (PDU), Children’s Hospital, Ain Shams University during the period from March 2023 to July 2023. It included 30 CKD-5d cases on OL-HDF for 3 months. All patients were receiving 3 sessions weekly with a 3-hour duration per session. Thirty age and sex matched healthy children were also enrolled as controls. Patients with the following medical conditions were excluded: failed renal graft, active infection, autoimmune disease, active thrombosis, diabetes mellitus, malignancy, cardiovascular disease like (infective endocarditis, vegetation and intracardiac mass) and patients on immunosuppressants. Complete blood cell (CBC), C-reactive protein (CRP) and serum NETs measured by ELISA were done for all cases pre- and post-OL-HDF as well as for the controls. Results The mean age of the cases was 12.2±2.8 years. They were 17 males (56.7%) and 13 females (43.3%). The mean age of the controls was 10.9±2.7 years. They were 15 males (50%) and 15 females (50%). Cases and controls were matched for age (p = 0.12) and sex distribution (p = 0.80). There was significantly elevated pre-OL-HDF (960.42 ± 498.55ng/L) and post-OL-HDF (213.98 ± 84.60ng/L) serum NETs compared to its level (147.12 ± 51.73ng/L) in controls (p < 0.001 for both). There was also significantly lower post-OL- HDF level of serum NETs than its pre-OL-HDF one (p < 0.001). There was no significant difference in circulating NETs between males and females (p = 0.19). Neither pre-OL_HDF nor post-OL-HDF serum NETS levels had any significant correlation with patients’ age (r = 0.051, p = 0.80) or pump blood flow rate (rho=-0.02, p = 0.91) respectively. In addition, there was no significant correlation between serum NETs and total leukocyte count (r = 0.37, p = 0.07; r = 0.14, p = 0.50), absolute neutrophil count (rho=0.40, p = 0.05; r = 0.055, p = 0.79) and absolutes lymphocyte count (r = 0.10, p = 0.65; r = 0.22, p = 0.30) for pre-OL-HDF and post-OL-HDF measures respectively. Conclusion There was significant statistical evidence of reduction in circulating NETs following an OL-HDF session in children with CKD-5d. Despite this reduction, the post- OL-HDF level of circulating NETs was still significantly higher than controls. This means that OL-HDF ameliorates the inflammatory milieu in CKD-5d children.