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.
    No preview · Article · May 2007 · Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis
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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: The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.
    Preview · Article · Jul 2006 · Journal of the American Society of Nephrology
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