Serum sortilin as a potential diagnostic and therapeutic target for cardiovascular calcification in uremic patients: A single-center prospective and observational study.

BACKGROUND

Cardiovascular disease (CVD) is the principal cause of mortality in chronic kidney disease (CKD) patients. Vascular calcification (VC) and cardiac valve calcification (CVC) significantly contribute to the increased CVD incidence in uremic patients. This study sought to determine the relationship between serum sortilin protein and both VC and CVC in uremic patients.

METHODS

In this cross-sectional study, a total of 212 uremic patients were ultimately included. Serum sortilin levels were measured, and abdominal aortic calcification scores (AACS) were determined using the Kaupplia semi-quantitative method. Echocardiographic data to identify CVC were available for 160 patients. Correlation analysis, logistic regression, receiver operating characteristic (ROC) curve analysis, and survival curve analysis were conducted.

RESULTS

Serum sortilin levels were significantly elevated in patients with severe VC compared to those with mild or no calcification and healthy controls. Similarly, serum sortilin levels were higher in uremic patients with CVC compared to those without CVC and healthy controls. Ln(AACS + 1) was significantly correlated with Ln(sortilin + 1). CVC was also significantly correlated with serum sortilin. Serum sortilin was identified as an independent risk factor for AAC and CVC in uremic patients. When combined with age, hemoglobin, and the presence of osteoporosis, serum sortilin predicted AAC with an area under the curve (AUC) of 0.84, a sensitivity of 70 %, and a specificity of 85 %. For CVC prediction, combined with age, albumin, ALP, and DBP, the AUC was 0.86, with a sensitivity of 60 % and specificity of 95 %. Patients with elevated sortilin levels had a higher one-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE).

CONCLUSION

Elevated circulating sortilin levels are a potential predictive and promoting factor for both VC and CVC in uremic patients.