Neutrophil Activation and Neutrophil Extracellular Trap Formation in Dialysis Patients

Abstract

Rationale & ObjectiveThe removal of metabolic waste by passing blood through synthetic tubing and membranes generates an immune response, even with the most biocompatible materials available. We evaluated blood levels of neutrophil activation and cell death during dialysis to devise a set of markers by which future dialysis interventions might be measured for biocompatibility.Study DesignObservational, case control.Setting & Participants30 patients with end-stage kidney disease in Seattle, WA, evaluated during 30 dialysis procedures in out- and inpatient settings were compared with 27 healthy (negative) controls and 20 nondialysis patients with systemic lupus erythematosus as positive controls.Predictor(s)Blood levels of neutrophil activation (calprotectin and peroxidase activity) and cell death (cell-free DNA and neutrophil extracellular traps) were assayed.Outcome(s)Markers of neutrophil activation and cell death can be used to assess immune response during dialysis.Analytical ApproachDescriptive analysis and group comparisons.ResultsIntradialytic levels of neutrophil activation markers are higher than prehemodialysis levels (P < 0.05), demonstrating neutrophil activation during hemodialysis. Less neutrophil activation occurs with peritoneal dialysis (P < 0.05). Immunosuppressive treatment and anticoagulant therapy did not seem to affect the capacity of neutrophils to undergo activation with hemodialysis. Finally, levels of hemodialysis-induced neutrophil activation correlated with markers of endothelial activation (r = 0.44; P = 0.01).LimitationsLow sample size with heterogeneous patient cohort.ConclusionsNeutrophil activation occurs during hemodialysis, potentially contributing to endothelial inflammation and damage. Neutrophil activation markers are novel and sensitive measures of biocompatibility for improving dialysis. The removal of metabolic waste by passing blood through synthetic tubing and membranes generates an immune response, even with the most biocompatible materials available. We evaluated blood levels of neutrophil activation and cell death during dialysis to devise a set of markers by which future dialysis interventions might be measured for biocompatibility. Observational, case control. 30 patients with end-stage kidney disease in Seattle, WA, evaluated during 30 dialysis procedures in out- and inpatient settings were compared with 27 healthy (negative) controls and 20 nondialysis patients with systemic lupus erythematosus as positive controls. Blood levels of neutrophil activation (calprotectin and peroxidase activity) and cell death (cell-free DNA and neutrophil extracellular traps) were assayed. Markers of neutrophil activation and cell death can be used to assess immune response during dialysis. Descriptive analysis and group comparisons. Intradialytic levels of neutrophil activation markers are higher than prehemodialysis levels (P < 0.05), demonstrating neutrophil activation during hemodialysis. Less neutrophil activation occurs with peritoneal dialysis (P < 0.05). Immunosuppressive treatment and anticoagulant therapy did not seem to affect the capacity of neutrophils to undergo activation with hemodialysis. Finally, levels of hemodialysis-induced neutrophil activation correlated with markers of endothelial activation (r = 0.44; P = 0.01). Low sample size with heterogeneous patient cohort. Neutrophil activation occurs during hemodialysis, potentially contributing to endothelial inflammation and damage. Neutrophil activation markers are novel and sensitive measures of biocompatibility for improving dialysis.