Kidney Week

Abstract: TH-PO529

Increased Subset of Low-Density Granulocytes in Dialysis Patients Associated with the Degree of Abdominal Aorta Calcification

Session Information

• Bone and Mineral Metabolism: Basic
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 401 Bone and Mineral Metabolism: Basic

Authors

• Rodriguez-Carrio, Javier, Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Spain

Javier Rodriguez-Carrio,

• Carrillo-Lopez, Natalia, Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain

Natalia Carrillo-Lopez,

• Ulloa, Catalina, Division of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain

Catalina Ulloa,

• Seijo, Mariana, Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

Mariana Seijo,

• Rodriguez, Minerva, Division of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain

Minerva Rodriguez,

• Rodriguez-Suarez, Carmen, Division of Nephrology, Hospital Universitario Central de Asturias, Oviedo, Spain

Carmen Rodriguez-Suarez,

• Cannata-Andia, Jorge B., Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain

Jorge B. Cannata-Andia,

• Suarez, Ana, Area of Immunology, Department of Functional Biology, University of Oviedo, Oviedo, Spain

Ana Suarez,

• Dusso, Adriana S., Bone and Mineral Research Unit. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), REDinREN-ISCIII, Oviedo, Spain

Adriana S. Dusso,

Background

Although systemic inflammation increases the risk for adverse vascular outcomes in chronic kidney disease (CKD), the exact players remain unclear. The emerging evidence of the relevance of low density granulocytes (LDGs) in inflammatory conditions led us to evaluate whether LDGs may be associated with 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 16 CKD patients undergoing hemodialysis and 6 HC was recruited for replication. Defensin3a (DEF3a, a marker of 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 subsets were not associated with parameters of bone and mineral metabolism, time on dialysis, serum cytokines or treatments. The increased CD14-CD16-CD15+ correlated directly with Kauppila scores and DEF3a expression in 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 be a marker of LDG expansion. These findings support an unprecedented role for LDGs in CKD immunopathogenesis.

Funding

• Government Support - Non-U.S.