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Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). Analyses were replicated in an additional cohort. DEF3 (marker of early granulopoiesis) gene expression on PBMCs was quantified by qPCR. Total CD15+ LDGs and both CD14lowCD16+ and CD14−CD16− subsets were expanded in CKD. The relative frequency of the CD14−CD16− subpopulation was higher among the CD15+ pool in CKD. This alteration was stable over-time. The increased CD14−CD16−CD15+ paralleled Kauppila scores and DEF3 expression, whereas no association was found with CD14lowCD16+ CD15+. Both subsets differed in their CD11b, CD10, CD35, CD31, CD62L, IFNAR1 and CD68 expression, FSC/SSC features and nuclear morphology, pointing to different origins and maturation status. In conclusion, LDGs were expanded in CKD showing a skewed distribution towards a CD14−CD16−CD15+ enrichment, in association with vascular calcification. DEF3 expression in PBMC can be a marker of LDG expansion. Fil: Rodríguez Carrio, Javier. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA). Bone and Mineral Research Unit; España. Universidad de Oviedo; España Fil: Carrillo López, Natalia. Hospital Universitario Central de Asturias; España Fil: Ulloa, Catalina. Hospital Universitario Central de Asturias; España Fil: Seijo, Mariana. Hospital Universitario Central de Asturias; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rodríguez García, Minerva. Hospital Universitario Central de Asturias; España Fil: Rodríguez Suárez, Carmen. Hospital Universitario Central de Asturias; España Fil: Díaz-Corte, Carmen. Hospital Universitario Central de Asturias; España Fil: Cannata Andía, Jorge B.. Universidad de Oviedo; España. Hospital Universitario Central de Asturias; España Fil: Suárez, Ana. Universidad de Oviedo; España Fil: Dusso, Adriana. Hospital Universitario Central de Asturias; España

Emerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade. Vitamin D was decreased in RA (p