Evaluation of Peripheral Vascular Calcification and Serum Magnesium Level in a Group of Egyptian Hemodialysis Patients

Introduction: Vascular calcification is a risk factor for cardiovascular mortality in the general population. It is highly prevalent in end stage renal disease (ESRD) patients. Low magnesium (Mg) levels have been reported to have a strong association with vascular calcification in hemodialysis (HD) patients. The aims of this study were to evaluate the prevalence of vascular calcification and its relation to serum Mg concentration in a group of Egyptian HD patients. Methods: We studied 65 stable patients undergoing maintenance HD for more than 6 months. Vascular calcification was evaluated using hand roentgenography. Serum Mg, phosphorus, corrected calcium and intact parathyroid hormone (iPTH) levels were compared between patients with and without vascular calcification. Results: The study included 41 male and 24 female patients, aged 43-70 years. Vascular calcification was present in 38.5% of the patients. Mean serum Mg level was 2.88 ± 0.51 mg/dl. Male gender was more common in patients with vascular calcification, and they had significantly longer HD duration and significantly higher serum phosphorus and iPTH levels. Serum Mg level was significantly lower in patients with vascular calcification (2.36 ± 0.26 mg/dl vs.3.21 ± 0.32 mg/dl, p = 0.001). Serum Mg concentration remained as independent negative predictor of hand-artery vascular calcification after adjustment for age, gender, duration of HD, serum phosphorus and iPTH levels. Conclusion: Vascular calcification is common in the study population and is associated with a lower serum Mg level. High or sustained-normal Mg levels may have a protective role against the development of vascular calcification in HD patients. Keywords: hemodialysis; magnesium; renal failure; vascular calcificatio

Mechanisms and Clinical Consequences of Vascular Calcification

Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health

Association of Serum Phosphate and Related Factors in ESRD-Related Vascular Calcification

Vascular calcification is common in ESRD patients and is important in increasing mortality from cardiovascular complications in these patients. Hyperphosphatemia related to chronic kidney disease is increasingly known as major stimulus for vascular calcification. Hyperphosphatemia and vascular calcification become popular discussion among nephrologist environment more than five decades, and many researches have been evolved. Risk factors for calcification are nowadays focused for the therapeutic prevention of vascular calcification with the hope of reducing cardiovascular complications

MicroRNAs Regulate Vascular Medial Calcification

Vascular calcification is highly prevalent in patients with coronary artery disease and, when present, is associated with major adverse cardiovascular events, including an increased risk of cardiovascular mortality. The pathogenesis of vascular calcification is complex and is now recognized to recapitulate skeletal bone formation. Vascular smooth muscle cells (SMC) play an integral role in this process by undergoing transdifferentiation to osteoblast-like cells, elaborating calcifying matrix vesicles and secreting factors that diminish the activity of osteoclast-like cells with mineral resorbing capacity. Recent advances have identified microRNAs (miRs) as key regulators of this process by directing the complex genetic reprogramming of SMCs and the functional responses of other relevant cell types relevant for vascular calcification. This review will detail SMC and bone biology as it relates to vascular calcification and relate what is known to date regarding the regulatory role of miRs in SMC-mediated vascular calcification

Vascular Calcification in Chronic Kidney Disease

Cardiovascular disease (CVD) is the major cause of death in chronic kidney disease (CKD). Of the various risk factors, vascular calcification has only recently come into prominence. CKD is associated with an increased risk of vascular calcification. In routine practice, clinicians usually overlook this finding. Screening for vascular calcification is often missed during first contact with nephrologists. With this article, we would like to reiterate the importance of preventing vascular calcification in early stages of CKD and once it starts appearing, its progression needs to be halted early with individualized treatment. The prevalence, sites of involvement, detection, quantification, pathogenesis, risk factors, clinical manifestations and management options have been discussed

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

<div><p>Hyperphosphatemia and vascular calcification are frequent complications of chronic renal failure and bone morphogenetic protein 7 (BMP7) has been shown to protect against development of vascular calcification in uremia. The present investigation examined the potential reversibility of established uremic vascular calcification by treatment of uremic rats with BMP7. A control model of isogenic transplantation of a calcified aorta from uremic rats into healthy littermates examined whether normalization of the uremic environment reversed vascular calcification. Uremia and vascular calcification were induced in rats by 5/6 nephrectomy, high phosphate diet and alfacalcidol treatment. After 14 weeks severe vascular calcification was present and rats were allocated to BMP7, vehicle or aorta transplantation. BMP7 treatment caused a significant decrease of plasma phosphate to 1.56 ± 0.17 mmol/L vs 2.06 ± 0.34 mmol/L in the vehicle group even in the setting of uremia and high phosphate diet. Uremia and alfacalcidol resulted in an increase in aortic expression of genes related to fibrosis, osteogenic transformation and extracellular matrix calcification, and the BMP7 treatment resulted in a decrease in the expression of profibrotic genes. The total Ca-content of the aorta was however unchanged both in the abdominal aorta: 1.9 ± 0.6 μg/mg tissue in the vehicle group vs 2.2 ± 0.6 μg/mg tissue in the BMP7 group and in the thoracic aorta: 71 ± 27 μg/mg tissue in the vehicle group vs 54 ± 18 μg/mg tissue in the BMP7 group. Likewise, normalization of the uremic environment by aorta transplantation had no effect on the Ca-content of the calcified aorta: 16.3 ± 0.6 μg/mg tissue pre-transplantation vs 15.9 ± 2.3 μg/mg tissue post-transplantation. Aortic expression of genes directly linked to extracellular matrix calcification was not affected by BMP7 treatment, which hypothetically might explain persistent high Ca-content in established vascular calcification. The present results highlight the importance of preventing the development of vascular calcification in chronic kidney disease. Once established, vascular calcification persists even in the setting when hyperphosphatemia or the uremic milieu is abolished.</p></div

Research Models for Studying Vascular Calcification

Calcification of the vessel wall contributes to high cardiovascular morbidity and mortality. Vascular calcification (VC) is a systemic disease with multifaceted contributing and inhibiting factors in an actively regulated process. The exact underlying mechanisms are not fully elucidated and reliable treatment options are lacking. Due to the complex pathophysiology, various research models exist evaluating different aspects of VC. This review aims to give an overview of the cell and animal models used so far to study the molecular processes of VC. Here, in vitro cell culture models of different origins, ex vivo settings using aortic tissue and various in vivo disease-induced animal models are summarized. They reflect different aspects and depict the (patho)physiologic mechanisms within the VC process

The impact of vascular calcification among dialysis dependent South African CKD patients. A five year follow up study. Cardiovascular mortality and morbidity, ethnic variation and hemodynamic correlates

BACKGROUND Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end stage renal disease (ESRD). In Western countries, Blacks with ESRD appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data on the association of ethnic differences in vascular calcification and survival in ESRD from Sub-Saharan Africa. METHODS This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score (lateral abdominal radiograph) and vascular stiffness by pulse wave velocity. RESULTS Sixty-six of the original 74 participants, studied a baseline, were identified. The median age was 46.6 years (37.6-59.2) and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks [baseline range 0-5, follow up range 0-8 (p=1.00)], but a nonsignificant trend to progression among non-Blacks [baseline range 0-19, follow up range 0-22 (p=0.066)]. Black participants did not display a survival advantage (p=0.870). Overall, sepsis was the most common cause of mortality (64% of those with an identifiable cause of death). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p=0.036). After adjustment for parathyroidectomy at follow up, the odds ratio of having abdominal vascular calcification score of ≥1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p= 0.03). Central aortic systolic pressures (CASP) and pulse wave velocities (PWV) were higher in the study population than age matched normative values. At follow up, a positive correlation (r=0.3) was observed between PWV and abdominal aortic calcification (p=0.04). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality. CONCLUSION There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks highlighting possible ethnic differences in calcium phosphate metabolism in patients with ESRD. The lack of vascular calcification progression in Blacks was not however associated with improved survival, but the sample size was small

Phosphate, oxidative stress, and nuclear factor-κB activation in vascular calcification

Phosphate-induced vascular calcification, characterized by induction of osteogenic programs, mineral vesicle release, and apoptosis, is prevalent in patients with kidney disease. Zhao et al. provide a mechanistic link between phosphate-induced calcification and increased mitochondrial membrane potential, increased mitochondrial reactive oxygen species, activation of the nuclear factor-κB pathway, and subsequent expression of osteogenic genes and vascular mineralization. This link clarifies the intracellular mechanism of vascular calcification and may allow exploration of antioxidants as therapeutic agents for vascular calcification