Calprotectin and CRP as biomarkers of cardiovascular disease risk in patients with chronic kidney disease: a follow-up study at 5 and 10 years

Abstract

Chronic kidney disease (CKD) and low-grade inflammation are associated with increased risk of cardiovascular disease (CVD). Calprotectin, a protein mainly secreted by activated neutrophils during inflammatory conditions, has been linked to CVD risk in general populations. The aim of this study was to evaluate the association of calprotectin with CVD risk in CKD patients, relative to C-reactive protein (CRP). One hundred and fifty-three patients with moderate CKD were prospectively followed up at 5 and 10 years. We used Cox regression modelling with stepwise adjustments for other relevant covariates (age, sex, cystatin C, previous CVD, systolic blood pressure, HDL cholesterol and HbA1c) to assess the association of baseline calprotectin and CRP with the risk of fatal or non-fatal CVD events. Twenty-nine and 44 patients experienced a CVD event during median follow-up of 4.8 and 10.9 years, respectively. Higher calprotectin was associated with increased CVD risk at both time points, which remained statistically significant after multivariable adjustments, including adjustment for CRP. For CRP, the associations did not remain statistically significant after final multivariable adjustments. In conclusion, we have shown that in patients with CKD, calprotectin was independently associated with the risk of future CVD events, suggesting that calprotectin may provide prognostic information of CVD risk.

Keywords:

• Calprotectin
• biomarkers
• neutrophils
• S100A8/A9 protein
• MRP8/14 protein
• CRP
• chronic kidney disease
• cardiovascular disease
• cardiovascular risk

Acknowledgements

The authors are grateful for the assistance from the Department of Nephrology and the Department of Clinical Chemistry at St. Olav’s University Hospital in recruiting patients for this study and managing blood test analysis.

Author contributions

L.L., V.V., G.G.H. and A.Å. contributed to the study concept and design. G.G.H. and L.L. contributed to the acquisition of data. L.L. and V.V. analysed and interpreted the data. L.L. drafted the manuscript. V.V. substantially revised the manuscript. G.G.H. and A.Å. revised the manuscript for important intellectual content. All authors approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The Clinic of Laboratory Medicine at St. Olav’s University Hospital funded this work.