Comparison of surgically removed cardiac valves of patients with ESRD with those of the general population.
ABSTRACT Patients with end-stage renal disease (ESRD) have increased vascular and valvular calcification compared with the general population. Recently, 44% of renal transplant recipients were found to have vascular calcification of the medial layer of the inferior epigastric artery that was associated with deposition of bone matrix proteins. Similar findings have been reported for native and bioprosthetic cardiac valves surgically removed from patients without ESRD.
To determine whether valvular calcification in patients with ESRD is similar to that in patients without ESRD, we retrospectively examined surgically excised native cardiac valves of all hemodialysis patients and compared them pathologically with those of matched controls without renal failure. Valves were examined by using routine stains and immunohistochemistry for markers to endothelial cells, macrophages, B and T lymphocytes, alkaline phosphatase, osteopontin, and bone morphogenic protein 4.
Histologically, 7 of 10 valves from patients with ESRD had moderate to severe inflammation compared with 1 of 10 valves from control patients. Patients with ESRD had more endothelial cells/vascularity (P = 0.002) and macrophages (P = 0.069). There was no difference between the 2 groups with respect to B and T lymphocytes, alkaline phosphatase, osteopontin, or bone morphogenic protein 4.
The noncollagenous proteins bone morphogenic protein and osteopontin have been shown in surgically removed cardiac valves of patients with ESRD and the general population. However, valvular calcification in patients with ESRD is associated with enhanced inflammation, consistent with the previously reported greater C-reactive protein levels in this patient population and their increased risk for death.
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ABSTRACT: A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase-1 (HO-1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non-HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD31, CD163, and HO-1. Morphometric analysis demonstrated that the CD163-positive macrophage score, the number of CD31-positive microvessels, and the percentage of glycophorin-A and HO-1-positive area were significantly higher in HD patients than in non-HD patients (CD163-positive macrophage score, P < 0.0001; CD31-positive microvessels, P < 0.0001; glycophorin-A, P < 0.0001; HO-1, P < 0.0001). Double immunostaining for CD163 or HO-1 and macrophages revealed that the majority of CD163- or HO-1-positive cells were macrophages. Furthermore, CD163-positive macrophage score was positively correlated with glycophorin-A, HO-1-positive area, and the number of CD31-positive microvessels (glycophorin-A, R = 0.66, P < 0.0001; HO-1, R = 0.50, P < 0.0005; microvessels, R = 0.38, P < 0.01). These findings suggest a positive association among intraleaflet hemorrhage, neovascularization, and enhanced expression of CD163 and HO-1 as a response to intraleaflet hemorrhage in stenotic aortic valves in AS patients undergoing HD.Hemodialysis International 02/2014; · 1.44 Impact Factor
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ABSTRACT: Cardiac valve calcification (VC) is a frequent complication in chronic renal disease and is considered a risk factor for all-cause and cardiovascular mortality. However, little is known about the pathophysiology mechanisms that originate it and the factors associated with its development. We undertook this study to analyze the frequency and factors related to de novo development of mitral valve calcification (MVC) and aortic valve calcifications (AVC) in incident peritoneal dialysis (PD) patients. A prospective cohort of 124 incident PD patients was studied. Demographic and clinical data were recorded and blood assayed at baseline and after 1 year of follow-up for calcium, phosphorus, glucose, urea, creatinine, cholesterol, triglycerides by spectrophotometry assay; high-sensitivity C-reactive protein (CRP) by immunoturbidimetric ultrasensitive assay, intact parathormone (iPTH) and osteocalcin by electrochemiluminescence, fetuin-A and osteoprotegerin by EDI-ELISA. Valve calcification was evaluated by M-mode bidimensional echocardiogram. Sixty eight percent of patients were male, ages 43 ± 13 years; 51% were diabetic with 1.4 ± 1 months on PD. After 12.3 ± 1 months, 57 patients (46%) developed VC: AVC in 33 (57.8%), MVC in 15 (26.3%) and 9 (15.8%) patients in both valves. There was no correlation between AVC and MCV. In univariate logistic regression analysis, age, diabetes and elevated concentrations of OPG, iPTH and CRP were risk factors for development MVC. In multivariate analysis, only iPTH remained an independent risk factor as was also the case in AVC. Age, diabetes, osteoprotegerin, parathormone and C-reactive protein are risk factors related to de novo development of MVC and iPTH for AVC in incident dialysis patients.Archives of medical research 11/2013; · 1.88 Impact Factor
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ABSTRACT: The aim of this study was to determine the effects of advanced chronic kidney disease (CKD) on early and late outcomes after transcatheter aortic valve implantation (TAVI), and to evaluate the predictive factors of poorer outcomes in such patients. This was a multicentre study including a total of 2075 consecutive patients who had undergone TAVI. Patients were grouped according the estimated glomerular filtration rate as follows: CKD stage 1-2 (≥60 mL/min/1.73 m(2); n = 950), stage 3 (30-59 mL/min/1.73 m(2); n = 924), stage 4 (15-29 mL/min/1.73 m(2); n = 134) and stage 5 (<15 mL/min/1.73 m² or dialysis; n = 67). Clinical outcomes were evaluated at 30-days and at follow-up (median of 15 [6-29] months) and defined according to the VARC criteria. Advanced CKD (stage 4-5) was an independent predictor of 30-day major/life-threatening bleeding (P = 0.001) and mortality (P = 0.027), and late overall, cardiovascular and non-cardiovascular mortality (P < 0.01 for all). Pre-existing atrial fibrillation (HR: 2.29, 95% CI: 1.47-3.58, P = 0.001) and dialysis therapy (HR: 1.86, 95% CI: 1.17-2.97, P = 0.009) were the predictors of mortality in advanced CKD patients, with a mortality rate as high as 71% at 1-year follow-up in those patients with these 2 factors. Advanced CKD patients who had survived at 1-year follow-up exhibited both a significant improvement in NYHA class (P < 0.001) and no deterioration in valve hemodynamics (P = NS for changes in mean gradient and valve area over time). Advanced CKD was associated with a higher rate of early and late mortality and bleeding events following TAVI, with AF and dialysis therapy determining a higher risk in these patients. The mortality rate of patients with both factors was unacceptably high and this should be taken into account in the clinical decision-making process in this challenging group of patients.European Heart Journal 05/2014; · 14.10 Impact Factor