Prevalence Of Vascular Calcification Research Articles

Vascular calcification in patients with nondialysis CKD over 3 years.

Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.

Early and Rarely - A Unique Case of Calcification in Stage 2 Chronic Kidney Disease.

A 60-year-old male presented to the hospital with ischemic heart disease (IHD), unstable angina and acute left ventricular failure. The patient had a history of diabetes mellitus (DM) and hypertension for last 10 years. He was also found to have renal dysfunction for last four months (CKD stage 2). Patient was taken for diagnostic coronary angiography, after taking precautions to prevent contrast induced nephropathy (CIN). For coronary angiography, femoral route was navigated initially, but the wire did not cross the lesion, so radial route was opted for performing angiography. The coronary angiogram revealed extensive calcification of all coronary arteries. Left anterior descending (LAD) artery and left circumflex (LCX) artery showed insignificant disease but proximal mid right coronary artery (RCA) junction showed 80% stenosis [Table/Fig-1,​,2].2]. We also observed unusual ‘round magic ball’ like appearance of extensive aortic calcification. [Table/Fig-1]: Right coronary artery (RCA) calcification [Table/Fig-2]: Calcification of aorta, left main coronary artery (LMCA), left anterior descending (LAD) artery and left circumflex artery (LCX) The term ‘chalky arteries’ is no more a ‘rare’ term when, debating about chronic kidney disease. The aortic and vascular calcification is an active metamorphic process involving phenotypic change of vascular smooth muscle cells (VSMCs) into bone forming cells. A fusillade of various events like high phosphate environment, excess of calcium, high dose of active vitamin D therapy and increased expression of osteoblastic markers like Runx-2, alkaline phosphatase and osteocalcin causes mineralization of VSMCs [1]. After phenotypic change in VSMCs and production of bone matrix protein, the role of matrix vesicles and apoptotic bodies come into picture to concentrate calcium and phosphate in preparation for mineralization [2]. The voluminous literature demonstrates that prevalence of vascular calcification (VC) in CKD patients ranges from 47% to 92% [3]. But, the prevalence is mostly spotted in end stage renal disease (ESRD) [4]. A study reported the prevalence of coronary artery calcification (CAC) in young dialysis and peritoneal dialysis patients to be 80% [5]. The uniqueness of the case lies in the stage of chronic kidney disease, at which extensive calcification was observed. The aortic and coronary calcification in our case is seen in stage 2 of CKD, which is considered to be quite germinal for calcification. But still, in one of the pre-clinical studies, it was demonstrated that CKD stimulated vascular calcification begins early in the disease prior to even hyperphosphatemia [6]. The early stimulated calcification process worsens as the disease progresses [7]. This holds ground for our case, but the extensive calcification observed in all the coronary arteries [Table/Fig-1,2] at stage 2 CKD, directs us to look beyond the obvious. In a study by Yamada et al., multivariate logistic regression analysis was carried out, and it demonstrated that CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices [8]. In our case, the patient has hypertension and DM for last 10 years. These co-morbid conditions may act as aggravating factors, along with CKD, in early predisposition of aortic and vascular calcification. The other typical presentation of the case is ‘round magic ball’ like appearance of aortic calcification [Table/Fig-2]. Usually, the calcification is present in the form of pigmentation adhered to the wall. But in our case, it is observed as round ball of calcified tissue in aorta. To the best of our knowledge, till now, none of the cases have reported such a distinct and startling ball-like calcification of aorta. In such cases, radial route should be preferred over femoral route. In our case, we initially tried femoral route, but the wire did not cross the calcific part of aorta at the junction of aortic arch and descending aorta. Aggressive manipulation in that part may lead to cerebral embolism. The radial route overcomes the junction of aortic arch & descending aorta, thereby reducing the chances of cerebral embolism. To sum up, the case provides insight into a different aspect, where calcification seems not only a threat to ESRD patients, but also as an early culprit. Aortic and vascular calcification in patients with CKD is a multifactorial interwining process, the pathologic mechanisms leading to such early calcification still remains to be elucidated.

Vascular calcification in long‐term kidney transplantation

Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.

Abdominal aortic calcification is not superior over other vascular calcification in predicting mortality in hemodialysis patients: a retrospective observational study.

BackgroundKDIGO (Kidney Disease: Improving Global Outcomes) guidelines recommend that a lateral abdominal radiograph should be performed to assess vascular calcification (VC) in dialysis patients. However, abdominal aortic calcification is a prevalent finding, and it remains unclear whether other anatomical areas of VC can predict mortality more accurately.MethodsA total of 217 maintenance hemodialysis patients were enrolled at the Sichuan Provincial People’s Hospital between July 2010 and March 2011. Radiographs of the abdomen, pelvis and hands were evaluated by a radiologist to evaluate the presence of VC. The correlation between different areas of VC and all-cause or cardiovascular mortality was analyzed using univariate and multivariate models.ResultsThe prevalence of VC was 70.0% (152 patients), and most had abdominal aortic calcification (90.1%). During 26 ± 7 months of follow-up, 37 patients died. The VC score was independently associated with patient mortality. VC observed on abdominal radiographs (abdominal aortic calcification) was associated with all-cause mortality in models adjusted for cardiovascular risk factors (HR, 4.69; 95%CI, 1.60-13.69) and dialysis factors (HR, 3.38; 95%CI, 1.18-9.69). VC in the pelvis or hands was associated with all-cause mortality in the model adjusted for dialysis factors. When three combinations of VC in different radiographs were included in models, the presence of abdominal VC was only significantly associated with all-cause mortality in the integrated model. VC in the abdomen and pelvis was associated with all-cause mortality in the model adjusted for cardiovascular factors and the integrated model, but neither was significantly associated with cardiovascular mortality. VC in all radiographs was significantly associated with a more than 6-fold risk of all-cause mortality and a more than 5-fold risk of cardiovascular mortality compared to patients without VC.ConclusionsVC in different arteries as shown on radiographs is associated with different levels of risk for mortality. The lateral abdominal radiograph may not be superior to other radiographs for predicting patient outcomes. Further research is needed to elucidate the effects of difference burdens of VC on patient outcomes.

ASSOCIATION OF CALCIFEDIOL LEVELS WITH VERTEBRAL FRACTURES, VASCULAR CALCIFICATIONS AND MORTALITY.

The best biomarker of Vitamin D status is calcifediol [25(OH)D]. We investigated the relationship between serum calcifediol levels and vertebral fractures (VF), vascular calcifications (VC) and mortality in hemodialysis patients. Within a multicenter, cross-sectional study in 18 hospital based dialysis centers in Italy, we included 387 hemodialysis patients (143 F, 37% ; 244 M, 63%), mean age 64±14 (SD) years, median dialytic age 49 months, BMI 25± 4 Kg/m2. We determined total 25(OH)D using the LIASON® 25 OH Vitamin D kit (DiaSorin Inc., Stillwater MN, USA). We evaluated VF with a computerized analysis of scanned L-L vertebral X-rays (T4 to L5). Reduction of > 20% of vertebral body height was considered a VF, while reductions between 15% and 20% were considered borderline fractures (BF). Fracture severity was estimated as mild, moderate or severe (reduction: 20–25%, 25–40% or >40%, respectively). VC assessments were also centralized. Witteman’s method (Lancet, 1994) was used for blinded assessments in duplicate. VC were quantified by measuring the length of calcific deposits along the anterior and posterior wall of the aorta (mild 0.1-5 cm, moderate 5.1-10 cm and severe >10 cm). We also evaluated the presence or absence of calcifications of the iliac arteries in the same radiograph (mild 0.1-3 cm, moderate 3.1-5 cm and severe >5cm). Any differences in VC were resolved by consensus. Follow up was 2.7±0.5 years. Bone markers were: Ca 9.15±0.68 mg/dl, P 4.8± 1.28 mg/dl, median ALP 83 U/L and median PTH 244 pg/ml. We found a median 25(OH)D level of 28.9 ng/ml. Nine ( 2.3%) patients had vitamin D deficiency ( 30 ng/ml). We found that 55% of patients had VF and 30.9% of patients had BF. Prevalence of VC was 80.6% (mild 20.1%, moderate 30.8%, severe 29.7%) in the aorta and 55,1% in the iliac arteries. Males had more VF than Females (60% versus 48%, P=0.019). No associations were found between VF and biochemical parameters including calcifediol levels (p=0.662), while we found an association between low calcifediol levels and a higher prevalence of severe aortic calcifications (36.8 vs 28.2, p=0.0044). Furthermore, we found a OR 1.85 (1.04-3.29 CI, p=0.0367) for Aortic Calcification in patients with calcifediol levels lower than the median value of 29 ng/ml. During follow-up (2.7±0.5 years) mortality was of 19.9%. No association was found between mortality and calcifediol levels (p=0.5394). In conclusion, despite good control of bone and mineral metabolism parameters, hemodialysis patients showed high prevalence of VF and VC. Our study suggests that high calcifediol levels could be protective against progression of severe aortic calcification

CABG in CKD: untangling the letters of risk

Chronic kidney disease (CKD) is an independent risk factor for coronary artery disease (CAD) and is associated with poor prognosis in patients with CAD [1,2]. The traditional risk factors such as hypertension, diabetes and dyslipidaemia are highly prevalent among CKD patients and contribute to severity of CAD [3]. Outcomes of acute coronary syndromes (unstable angina and myocardial infarction) are worse for CKD patients than for patients with preserved renal function [4,5]. The prognosis for patients with impaired renal function who undergo coronary revascularization, either percutaneous coronary intervention or coronary artery bypass grafting (CABG), worsens as estimated glomerular filtration rate (eGFR) deteriorates [6–10]. Given the outcomes of CKD patients undergoing CABG, the opportunity to risk-stratify them before surgery would carry important clinical implications. Numerous factors have been cited to explain the association between renal dysfunction and cardiovascular events. Impaired renal function is associated with reduced erythropoietin synthesis and consequent anaemia, which has been associated with cardiovascular disease [11]. Reduced 1,25 (OH) vitamin D production is associated with increased parathyroid hormone levels and higher prevalence of vascular calcification and arteriosclerosis [12]. CKD patients face additional challenges in the setting of coronary revascularization. Increased co-morbidity, reduced use of standard cardiovascular therapies, and more advanced valvular and myocardial disease all account for worse outcomes after CABG [13]. In this issue of Nephrology Dialysis Transplantation, Charytan et al. propose a risk score model for CKD patients undergoing CABG [14]. The data source is a retrospective analysis of 2438 patients undergoing CABG at a single centre between 2005 and 2008. Patients were stratified based on severity of renal dysfunction: normal renal function/mild CKD (stages 1–2; eGFR ≥60 mL/min/ 1.73 m 2 ; n = 1714), moderate CKD (stage 3; eGFR 30–

Chronic kidney disease (CKD) and bone. Impact of diabetes mellitus on the development of CKD-MBD

Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops as renal function deteriorates. The presence of diabetes mellitus as comorbidity modulates the severity of CKD-MBD. The prevalence of vascular calcification, which becomes higher in diabetic CKD patients than in non-CKD counterparts, increases cardiovascular mortality in diabetic patients. The main factor which causes vascular calcification in diabetic CKD patients is poor glycemic control, in contrast to hyperphosphatemia in non-diabetic CKD patients. Diabetes directly impairs osetoblasts to decrease bone mass, suppresses bone turnover to impair bone quality by impairing secretion of parathyroid hormone and increase AGE-modification of bone collagen. Therefore, therapeutic regimens for CKD-MBD should be considered specifically for diabetic CKD patients since the mode of its development differs between diabetic and non-diabetic CKD patients.

The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer

Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.

Gene Polymorphism Association Studies in Dialysis: The Nutrition‐Inflammation Axis

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.