Reducing the Burden of Cardiovascular Calcification in Patients with Chronic Kidney Disease

Department of Medicine, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 12/2005; 16 Suppl 2(11):S95-102. DOI: 10.1681/ASN.2005060666
Source: PubMed


Patients with chronic kidney disease (CKD) have a higher burden of atherosclerotic coronary artery disease compared with age- and gender-matched individuals with normal renal function. Cardiovascular calcification (CVC), a marker of atherosclerosis, is also more prevalent in these patients and is associated with serious clinical consequences. The pathogenesis of CVC is complex and includes factors that promote calcification and others that inhibit calcification. Thus, multiple therapeutic interventions should be used simultaneously to reduce the burden of calcification in patients with CKD. Thus far, interventional attempts have focused on curtailing the effects of factors that promote calcification such as management of known traditional factors for atherosclerotic coronary artery disease and on adopting specific approaches to normalize mineral metabolism, deliver adequate dialysis, and control serum cholesterol level. By contrast, interventions that may bolster the effects of inhibitors of calcification have not yet been studied well but are beginning to attract attention. Ideally, the goal of interventions is not only to slow or halt progression of calcification but also to reverse pre-existing calcification. Whether this goal is achievable is not currently known. This review examines the potential of various therapeutic interventions in reducing the CVC burden in patients with CKD. Moreover, the review is intended to stimulate more research in this area because the efficacy of these interventions has not been examined in controlled clinical trials.

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    ABSTRACT: Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3-2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.
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    ABSTRACT: Cardiovascular disease (CVD) is very common in patients with chronic kidney disease (CKD) and is by far the leading cause of morbidity and mortality in dialysis patients [1]. The National Health And Nutrition Epidemiology Survey (NHANES III) estimated that 11% of adults in the United States have CKD [2]. World-wide, 5-10% of the world's population may also have CKD, a staggering 300-600 million people [3]. Of the major outcomes of CKD, progression to ESRD has attracted the most attention. However, the development of CVD is more serious since only a small fraction of patients with CKD progress to ESRD and requires renal replacement therapy such as dialysis or renal transplantation. The majority of patients, particularly those with an estimated glomerular filtration rate (eGFR) of <60 ml/min, usually die from heart disease before they reach ESRD [4,5]. This was clearly shown by Keith et al [4] who analyzed outcomes of 27,998 patients with evidence of CKD and found that the 5-year mortality rates for CKD stages 2, 3, and 4 were 19.5, 24.3, and 45.7% respectively; while the percentages of patients with these stages who progressed to ESRD were much lower at 1.1%, 1.3%, and 19.9%. Similarly, CVD is very common in dialysis patients and accounts for almost 50% of deaths, a rate that is 20 to 30 fold higher than age, gender and race matched controls [1]. The risk of CVD is even higher in children and young adults with ESRD in whom the mortality rate from CVD is almost 100 times greater than in the general population. Thus, CKD clearly represents a major public heath problem. Evidence for the increased prevalence of CVD in CKD was derived from both prospective and retrospective community-based epidemiologic studies. Weiner et al pooled data from four community-based longitudinal studies to assess whether CKD was an independent risk factor for cardiovascular events [6]. They concluded that CKD is an independent risk factor for the composite outcome of all-cause mortality and CVD. In another study, it was shown that a decrease in eGFR by 5 mL/min/1.73m 2 was associated with a 26% increase in cardiovascular death [7]. Even mild reduction of renal function is associated with significant increase in cardiovascular morbidity and mortality in a post-myocardial infarction population [Figure 1] [8].
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    ABSTRACT: Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.
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