Reducing the burden of cardiovascular calcification in patients with chronic kidney disease.
ABSTRACT 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.
- SourceAvailable from: Gholam Hossein Kazemzadeh[Show abstract] [Hide abstract]
ABSTRACT: Little is known about the incidence of temporary kidney dysfunction following major vascular surgeries. We aimed to assess the frequency of temporary decreased kidney function following aortic surgeries. In a retrospective study, we assessed 108 hospital records of the patients who had undergone elective open abdominal surgery of aortic aneurysm. Preoperative and postoperative (days 1, 2, and 3) data on estimated glomerular filtration rate (GFR) were collected and evaluated in relation to the patients' clinical characteristics and outcomes. A decline greater than 10% in GFR on day 1 or 2, and then, an increase of GFR to a level of maximum 10% below the baseline value on the third postoperative day was considered as temporary worsening of kidney function. Postoperative alterations of GFR not greater than 10% in relation to the baseline were considered as improved or unchanged kidney function. Two patients with persistent decrease in GFR were excluded. Temporary worsening of kidney function was seen in 25 patients (23.6%). Short-term mortality rate was 44.0% in this group of patients, while it was 17.3% in those without decreased GFR (P = .006). According to the regression analysis, the only predictor of mortality was temporary worsening of kidney function, with a hazard ratio of 4.03 (95% confidence interval, 1.44 to 11.31; P = .008). Nearly 1 out of 4 aortic surgeries results in kidney dysfunction. Albeit temporary in most cases, it seems to be associated with a higher short-term mortality rate.Iranian journal of kidney diseases 08/2008; 2(3):143-8. · 0.94 Impact Factor
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ABSTRACT: Medial artery calcification in patients with chronic kidney disease proceeds through intramembranous ossification resulting from osteoblast-induced calcification of the collagen extracellular matrix. The current study is based on the hypothesis that mesenchymal stem cells (MSC) constitute critical cells for procalcific extracellular matrix remodeling in patients with chronic kidney disease. Human MSC were cultured in media supplemented with pooled sera from either healthy or uremic patients (20%). Exposure to uremic serum enhanced the proliferation of MSC (cell counting, BrdU incorporation) whereas apoptosis and necrosis were not affected (annexin V and 7-amino-actinomycin staining). Uremic serum-exposed MSC recapitulated osteogenesis by matrix calcification and expression of bone-related genes (bone morphogenetic protein [BMP]-2 receptor, alkaline phosphatase, osteopontin, and Runx2) in 35 days. The uremic serum-induced osteogenesis was completely blocked by a BMP-2/4 neutralizing antibody or the natural antagonist NOGGIN. Calcification and matrix remodeling were further analyzed in a collagen-embedded osteogenesis model recapitulating the vascular collagen I/III environment. The uremic serum-induced calcification was shown to occur along collagen fibers as shown by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and von Kossa staining and was accompanied by extensive matrix remodeling. Uremic serum induced in a BMP-2/4-dependent manner an osteoblast-like phenotype in MSC accompanied by matrix remodeling and calcification.Arteriosclerosis Thrombosis and Vascular Biology 06/2011; 31(9):e45-54. · 6.34 Impact Factor
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ABSTRACT: HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular CV outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their pleiotropic effects statins have been shown to reduce inflammation, alleviate oxidative stress, modify the immunologic responses, improve endothelial function and suppress platelet aggregation. Patients with chronic kidney disease (CKD) exhibit an enormous increase in CVD rates even from early CKD stages. As considerable differences exist in dyslipidemia characteristics and the pathogenesis of CVD in CKD, statins' CV benefits in CKD patients (including those with a kidney graft) should not be considered unequivocal. Indeed, accumulating clinical evidence suggests that statins exert diverse effects on dialysis and non-dialysis CKD patients. Therefore, it seems that statins improve CV outcomes in non-dialysis patients whereas exert little (if any) benefit in the dialysis population. It has also been proposed that dyslipidemia might play a causative role or even accelerate renal injury. Moreover, ample experimental evidence suggests that statins ameliorate renal damage. However, a high quality randomized controlled trial (RCT) and metaanalyses do not support a beneficial role of statins in renal outcomes in terms of proteinuria reduction or retardation of glomerular filtration rate (GFR) decline.Pharmacological research : the official journal of the Italian Pharmacological Society. 07/2014;