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Updated: Jun 11, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
The vitamin D system: a crosstalk between the heart and kidney
Mario Cozzolino1, Markus Ketteler, Daniel Zehnder
1Renal Division, S. Paolo Hospital, University of Milan, Via A. di Rudin'ı, 8-20142 Milan, Italy. mariocozzolino@hotmail.com
Insights
Chronic kidney disease (CKD) increases cardiovascular disease risk. Vitamin D receptor (VDR) activators may reduce cardiovascular morbidity and mortality in CKD patients by addressing VDR signaling impairment.
Area of Science:
- Nephrology
- Endocrinology
- Cardiology
Background:
- Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD), with severity correlating to increased CVD morbidity and mortality.
- Vitamin D, activated in the liver and kidneys by CYP27B1, exerts actions via the vitamin D receptor (VDR).
- VDR and CYP27B1 are expressed in cardiovascular, immune, and epithelial tissues, influencing endothelial, vascular smooth muscle, and cardiac cell function, as well as inflammatory and fibrotic pathways.
Purpose of the Study:
- To explore the role of vitamin D receptor (VDR) signaling in cardiovascular health, particularly in the context of chronic kidney disease (CKD).
- To highlight the implications of impaired VDR activation in CKD-MBD and its contribution to cardiovascular complications.
- To discuss the potential of VDR activators in mitigating cardiovascular morbidity and mortality in CKD patients.
Main Methods:
- Review of existing literature on vitamin D metabolism, VDR signaling, and its impact on cardiovascular and renal systems.
- Analysis of the relationship between CKD, CKD-MBD, and cardiovascular disease.
- Examination of the therapeutic potential of VDR activators in managing CKD-related cardiovascular risks.
Main Results:
- Impaired VDR activation leads to cellular dysfunction, contributing to reduced bone health, increased cancer risk, metabolic disease, and inflammation.
- Failure of VDR activation in the cardiovascular system results in hypertension, accelerated atherosclerosis, vascular calcification, cardiac hypertrophy, and renal dysfunction.
- Emerging evidence supports a link between CKD, CKD-MBD, and CVD, influencing clinical guidelines.
Conclusions:
- Vitamin D receptor (VDR) signaling plays a critical role in cardiovascular health, and its impairment in CKD contributes to significant morbidity and mortality.
- Vitamin D receptor activators, used in managing CKD-MBD, may offer a therapeutic strategy to reduce cardiovascular complications in CKD patients.
- Optimizing vitamin D hormonal system function is crucial for improving cardiovascular outcomes in individuals with chronic kidney disease.
Abstract:
Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.
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