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Published on: June 2, 2022
Serum sortilin as a potential diagnostic and therapeutic target for cardiovascular calcification in uremic patients:
Yuxia Zhang1, Jingjing Chen2, Yan Di2
1School of Medicine, Southeast University, Nanjing, China; Department of Nephrology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University School of Medicine, Nanjing, China.
Insights
Elevated serum sortilin levels are linked to vascular calcification (VC) and cardiac valve calcification (CVC) in patients with chronic kidney disease. Higher sortilin may predict cardiovascular events in these high-risk individuals.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Cardiovascular disease (CVD) is the leading cause of death in chronic kidney disease (CKD) patients.
- Vascular calcification (VC) and cardiac valve calcification (CVC) are major contributors to CVD in uremic individuals.
Purpose of the Study:
- To investigate the association between serum sortilin levels and VC and CVC in uremic patients.
- To evaluate sortilin as a potential biomarker for cardiovascular complications in CKD.
Main Methods:
- Cross-sectional study including 212 uremic patients.
- Measurement of serum sortilin levels and abdominal aortic calcification scores (AACS).
- Echocardiography for CVC assessment; correlation, regression, and ROC curve analyses were performed.
Main Results:
- Serum sortilin was significantly elevated in patients with VC and CVC compared to controls.
- Serum sortilin levels correlated with AACS and were an independent risk factor for VC and CVC.
- Sortilin demonstrated predictive value for AAC and CVC, and elevated levels were associated with increased MACCE risk.
Conclusions:
- Elevated serum sortilin is a potential predictive factor for vascular and cardiac valve calcification in uremic patients.
- Sortilin may play a role in promoting calcification processes in CKD.
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.
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