Increased Subset of Low-Density Granulocytes in Dialysis Patients associated with the degree of abdominal aorta calcification

CARRILLO-LÓPEZ, NATALIA; MINERVA RODRIGUEZ; ANA SUAREZ; CATALINA ULLOA; RODRÍGUEZ-SUÁREZ, CARMEN; ADRIANA S. DUSSO; JAVIER RODRIGUEZ-CARRIO; MARIANA SEIJO; CANNATA-ANDIA JB

Congreso; Kidney Week 2019; 2019

Background: Although systemic inflammation increases the risk for adverse vascular outcomes in chronickidney disease (CKD), the exact players remain unclear. The emerging evidence of the relevance of lowdensity granulocytes (LDGs) in inflammatory conditions led us to evaluate whether LDGs may be associatedwith inflammatory/pro-calcifying features in CKD.Methods: LDGs subsets were identified by flow cytometry in peripheral blood mononuclear cells (PBMCs)from 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). An additional cohort of 16CKD patients undergoing hemodialysis and 6 HC was recruited for replication. Defensin3a (DEF3a, a markerof early granulopoiesis) gene expression on PBMCs was quantified by qPCR.Results: Total LDGs (CD15+) and both CD14lowCD16+ and CD14-CD16- subsets were increased in CKD.The relative frequency of the CD14-CD16- subpopulation among the total CD15+ pool was increased in CKD.Both LDG subsets differed in origin and maturation status as demonstrated by their CD11b, CD31, CD62L,Interferon receptor 1 (IFNAR1) and CD68 expression and size/granularity (FSC/SSC) features. LDGs subsetswere not associated with parameters of bone and mineral metabolism, time on dialysis, serum cytokines ortreatments. The increased CD14-CD16-CD15+ correlated directly with Kauppila scores and DEF3a expressionin PBMCs, whereas no association was found with CD14lowCD16+CD15+.Conclusion: CKD is associated with elevated LDGs, showing a skewed distribution towards a CD14-CD16-CD15+ enrichment in blood which correlated with vascular calcification. DEF3a expression in PBMC could bea marker of LDG expansion. These findings support an unprecedented role for LDGs in CKDimmunopathogenesis.