Chronic Kidney Disease, Coronary Arteries Calcifications, CXCR2 Expression
Conditions
Keywords
chronic kidney disease, coronary arteries calcifications, CXCR2 expression
Brief summary
Chronic kidney disease (CKD) is associated with the development of coronary arteries calcifications (CAC) and increased cardiovascular mortality. Previously, the investigators demonstrated that interleukin 8 (IL-8) plays a role in the calcification process, and that blockade of its receptor, CXCR2 reduces cardiovascular calcifications. The investigators hypothesize that leucocytes expressing CXCR2 may contribute to the development and progression of CAC in CKD patients. Identifying CKD patients with a high calcification phenotype and therapeutic targets to prevent cardiovascular calcifications is essential. Advanced CKD patients (stages IV and V) will undergo analysis of CXCR2 expression from neutrophils and monocytes at inclusion by flow cytometry, followed by non-contrast thoracic CT scans at inclusion, 1 year and 3 years to assess calcification scores and progression. Patients will have a pre-inclusion visit for research information and consent. If consent is given, three protocol visits (inclusion, 1 year, 3 years) including clinical exam, laboratory tests and CT evaluations will be performed.
Interventions
OTHERThoracic CT
Thoracic CT will be performed at inclusion, 1 year and 3 years to assess coronary calcification and aortic valve calcification scores and progression.
BIOLOGICALBlood samples
Blood samples will be collected at inclusion, 1 year and 3 years to measure CXCR1 and CXR2 expression on neutrophils and monocytes by flow cytometry.
Sponsors
Centre Hospitalier Universitaire, Amiens
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \> 18 years * CKD defined by eGFR \< 30 mL/min/1,73m² * signed inform consent
Exclusion criteria
* patients on dialysis, * kidney transplant recipients, * current or recent (within 30 days) infection, * inflammatory diseases, * active cancer treatment, * use of immunosuppressive agents, * presence of coronary stents or aortic valve protheses, * inability to provide informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| variation from baseline of CXCR2 expression | at 3 years | CXCR2 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells) from blood sample. |
| Correlation between CXCR2 expression and calcium score | at 3 years | The coronary calcification score will be determined by Agatston method. CXCR2 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells) from blood sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CXCR2 expression and the 1-year progression of the calcium score | at 1 year | The coronary calcification score will be determined by Agatston method. CXCR2 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells) from blood sample. |
| Correlation between CXCR1 or CXCR2 expression and calcium score trajectory | 1 year | The coronary calcification score will be determined by Agatston method. CXCR2 expression and CXCR1 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells and percentage of CXCR1 positive cells) from blood sample. |
| Correlation between CXCR2 expression and the calcium score progression in other vascular territories | at 3 years | The coronary calcification score will be determined by Agatston method. CXCR2 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells) from blood sample. |
| Correlation between CXCR1 expression and the calcium score progression in other vascular territories | at 3 years | The coronary calcification score will be determined by Agatston method. CXCR1 expression will be quantified by flow cytometry (percentage of CXCR1-positive cells) from blood sample. |
| Correlation between a CXCR1- or CXCR2-positive leukocyte phenotype and CKD progression | at 3 years | The coronary calcification score will be determined by Agatston method. CXCR2 expression and CXCR1 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells and percentage of CXCR1 positive cells) from blood sample. |
| Correlation between a CXCR1- or CXCR2-positive leukocyte phenotype and the occurrence of cardiovascular complications | at 3 years | CXCR2 expression and CXCR1 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells and percentage of CXCR1 positive cells) from blood sample. |
| Correlation between a CXCR1- or CXCR2-positive leukocyte phenotype and mortality | at 3 years | CXCR2 expression and CXCR1 expression will be quantified by flow cytometry (percentage of CXCR2-positive cells and percentage of CXCR1 positive cells) from blood sample. |
| Correlation between leukocyte phenotype and serum indoxyl sulfate concentration | at 3 years | — |
Countries
France
Contacts
CONTACTQuentin DE BERNY, MD
Outcome results
None listed