Calprotectin Is Associated with Vascular Calcification and Cardiovascular Complications During CKD

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https://storage.unitedwebnetwork.com/files/1099/d70ad15b31e1617bf1e10d20ef21c342.pdf

Abstract Title

First Name *

Serban

Last Name *

Ardeleanu

Co-author 1

Julie Klein juli.klein@inserm.fr INSERM Institute of Cardiovascular and Metabolic Disease Toulouse

Co-author 2

Ana Amaya-Garrido Amaya-Garrido juli.klein@inserm.fr INSERM Institute of Cardiovascular and Metabolic Disease Toulouse

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Introduction

In patients with chronic kidney disease (CKD), vascular calcification is considered a major risk factor of cardiovascular (CV) mortality. The mechanisms of vascular calcification are complex and treatment options remain limited. Serum proteome analysis could help identify novel actors and potential therapeutic targets.

Methods

In this observational, European, multicenter study, we included 112 CKD3- 4 patients from Spain, 171 dialysis patients from Toulouse and La Reunion (France), and 170 CKD5 patients from Sweden. Serum proteome analysis was performed using LC-MS/MS on a subset of 66 CKD3-4 patients. Circulating calprotectin concentration was validated in the serum or plasma from the full cohorts by ELISA. Calprotectin was associated with CV outcome (2-4 years of follow-up) or with vascular calcification score assessed by Von Kossa staining on a piece of epigastric artery collected during renal transplantation surgery. The effect of calprotectin on calcification was measured in primary human vascular smooth muscle cells (VSMCs) and mouse aortic rings. The anticalcific potential of calprotectin inhibitor paquinimod was studied in a 5/6 subtotal nephrectomy mouse model.

Results

We identified using serum proteome analysis and further validation by ELISA that calprotectin, a circulating damage-associated molecular pattern protein, was associated with vascular calcification, CV outcome and mortality in CKD and dialysis patients. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod inhibited the pro-calcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by serum of uremic patients in primary human VSMCs. Finally, treatment with paquinimod blocked vascular calcification in mice with chronic renal failure induced by 5/6 subtotal nephrectomy.

Conclusions

We identified calprotectin as a key factor associated with vascular calcification, CV outcome and mortality in CKD patients. Blockade of calprotectin by paquinimod might be a promising strategy to reduce the burden of vascular calcification in CKD.

These results have been presented as an oral presentation at the ASN Kidney Week in Philadelphia 2023.

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