Abstract
BACKGROUND: Patients with chronic kidney disease (CKD) are at increased cardiovascular risk. Since neutrophils play a central role in atherosclerosis and cardiovascular disease, this study analyzed neutrophil function in CKD patients. METHODS: A systematic review of neutrophil function in CKD patients compared to controls was performed according to PRISMA guidelines by searching PubMed and the Web of Science. A meta-analysis summarized the production of reactive oxygen species (ROS) in CKD patients on dialysis in Forest plots. Influencer outlier analyses evaluated risk of bias. RESULTS: Overall, 92 studies were included, of which 18 in the meta-analysis. Although study heterogeneity was high, the systematic review identified primarily reduced phagocytosis capacity but increased neutrophil degranulation and basal ROS production in neutrophils from CKD patients on hemodialysis compared to controls. Phagocytosis and basal ROS production were mainly unaltered in non-dialysis dependent CKD patients and CKD patients on peritoneal dialysis. The meta-analysis confirmed increased ROS generation in basal conditions predominantly in CKD patients on hemodialysis (Hedges g = 1.20, 95% CI: [0.32; 2.09]), with an insufficient study number for a clear comparison to CKD patients on peritoneal dialysis. However, upon neutrophil stimulation with sterile inflammatory triggers, ROS production was also increased in neutrophils from patients on peritoneal dialysis (Hedges g = 0.89, 95% CI: [0.34; 1.43]). CONCLUSION: Increased degranulation and basal ROS formation were observed in neutrophils of CKD patients on hemodialysis, which could contribute to their increased cardiovascular risk. Future studies should compare neutrophil activity in patients of different CKD stages and comorbidities also in relation to cardiovascular outcomes.