Calcification In Hemodialysis Patients Research Articles

Effect of vitamin K1 supplementation on matrix Gla protein level and vascular calcification in hemodialysis patients

BackgroundMatrix Gla protein (MGP) is a potent calcification inhibitor of the arterial wall. Its activity depends on vitamin K-dependent γ-carboxyglutamate.AimWe aimed to investigate the effect of vitamin K1 on MGP levels after 3 months’ supplementation and the relationship between MGP level and vascular calcification.Patients and methodsA prospective case–control pilot study was conducted overa period of 3 months. The study included 57 long-term hemodialysis patients in stable conditions who were divided into two groups and were compared with 27 healthy age-matched controls. Group I consisted of 28 hemodialysis patients who received vitamin K1 at10 mg three times per week for a successive period of 3 months. Group II consisted of 29 hemodialysis patients who did not receive vitamin K. Group III consisted of 27 healthy participants as controls. The serum level of MGP was measured by radioimmunoassay; in addition, hemoglobin%, parathyroid hormone, calcium, phosphorus, sodium, potassium, alkaline phosphatase, total cholesterol, triglyceride, and carotid intima–media thickness were also measured. Plain radiograph of the abdomen in lateral view was acquired to determine the abdominal aortic calcification score at the start of the study, which was reassessed after 3 months in groups I and II.ResultsWe found a significant increase in blood pressure, body mass index (BMI) with elevation in the serum level of MGP in patient groups than control from the start. A significant elevation in MGP level was observed in group I accompanied by a decrease in serum cholesterol level, compared with group II. We did not find any significant change in carotid intima–media thickness or abdominal aortic calcification score in either group after 3 months. There was no significant correlation between elevated MGP level and vascular calcification either. No significant difference was found in other parameters.ConclusionVitamin K supplementation may be essential for End Stage Kidney Disease (ESKD) patients on hemodialysis. Vitamin K can increase the level of MGP and decrease cholesterol level, but its beneficial effect on the vascular bed needs a long-term study.

Treatment of a soft tissue calcification in a patient receiving peritoneal dialysis

Chronic Kidney Disease patients suffer from Mineral and Bone Disorder (CKD-MBD) leading to increased vascular and soft-tissue calcification. The prevalence of soft tissue calcification in dialysis patients is not well described, and most cases describe such calcifications in hemodialysis patients. We describe a case of a massive soft tissue calcification in the right gluteal region in a peritoneal dialysis patient. The patient had severe pain and were disabled. The treatment was converted to an intensive hemodialysis regimen with a minimal calcium load and high dose of cinacalcet. During the treatment, the calcification diminished rapidly from a diameter of 26.6 to 2.9 cm, and the patient symptoms were relieved, leaving the patient with no pain or restriction in mobilization.

Complex Assessment of Risk Factors for the Development of Cardiovascular Calcification in Hemodialysis Patients

The aim of the present study was the integrated assessment of the role of non-traditional factors (inflammation, malnutrition, calcium-phosphorus disorder and imbalance in the concentration of inducers and inhibitors of calcification) in forming cardiovascular calcification (CVC) and the structural-functional rearrangement of LV myocardium in patients with chronic kidney disease (CKD) receiving hemodialysis (HD). Materials and Methods: The present study included 84 HD patients with CKD 5D stage. We evaluated 3 components of the Dialysis Malnutrition Score (DMS), according to which body mass index (BMI), the level of serum albumin, and the percent saturation of transferrin with iron were determined. We also analyzed CRP, fibrinogen, and beta-2 microglobulin, and calculated the number of points (from zero to 2) according to the Glasgow Prognostic Score (GPS), which allowed us to combine indicators of inflammation and make a common prognostic assessment. The serum levels of protein alpha-Klotho и FGF-23 were determined by enzyme immunoassay. Echocardiographic measurements were performed using B-mode, M-mode and Doppler-mode. Different patterns of LV geometry were identified according to Ganau et al. (1992). The severity of calcification was estimated by a semi-quantitative scale for assessing the degree of calcification of heart structures according to the National recommendations for CKD-MBD (2010). Results: The increased risk for development of CVC, LVH, and diastolic dysfunction was associated with markers of malnutrition, anemia, and inflammation in HD patients. Reduced serum alpha-Klotho level, hypoalbuminemia and a high level of FGF-23 had a prognostic value in CVC formation. (Int J Biomed. 2016;6(1):22-26.).

Circulating S100A12 Levels Are Associated with Progression of Abdominal Aortic Calcification in Hemodialysis Patients.

Vascular calcification is an important factor associated with mortality in dialysis patients. Recently, soluble receptor for advanced glycation end product (sRAGE) and extracellular RAGE binding protein S100A12 (EN-RAGE) have been reported to be involved in the process of vascular calcification. Therefore, we investigated whether sRAGE and S100A12 are useful indicators of progression of abdominal aortic calcification in hemodialysis (HD) patients. We analyzed annual changes in vascular calcification score (VCS) for up to 4 years, compared to clinical and biological parameters in 149 HD patients. VCS was assessed annually using plain X-ray images of the lateral lumbar spine. The progression group was defined as patients with an increase in VCS more than 1 point each year on average during the observation period. Time-averaged concentrations were also evaluated to examine the association between biological parameters and changes in VCS. The patients had a mean age of 58.59 ± 12.93 years; 53.7% were male, and 45% were diabetic. The VCS increased in 55 patients; the mean increase was 1.60 ± 2.91 points. In a stepwise multivariate logistic analysis, we found that higher levels of S100A12 were significantly associated with progression of VCS (odds ratio [OR], 2.622; 95% confidence interval [CI], 1.371–5.016; P = 0.004). The relationship between sRAGE and VCS was not statistically significant (OR, 0.644; 95% CI, 0.302–1.374; P = 0.255). Our findings suggest that serum levels of S100A12 are associated with progression of abdominal aortic calcification in HD patients, independent of sRAGE level.

Relationship Between Diastolic Dysfunction and Atherosclerosis and Vascular Calcification in Hemodialysis Patients: Diagnostic Potential of the Cardio-Ankle Vascular Index.

Diastolic dysfunction (DD) commonly causes heart failure with preserved ejection fraction (EF). Here, we examine associations between DD severity and atherosclerosis/vascular calcification in hemodialysis patients. Echocardiography was performed on 101 patients undergoing hemodialysis therapy. Twelve patients (EF < 50% or chronic atrial fibrillation) were excluded; DD of the remaining 89 patients was classified into four grades. We then investigated the relationship between their DD grades and the cardio-ankle vascular index (CAVI), ankle-brachial pressure index (ABI), toe-brachial pressure index (TBI), and aortic calcification area index (ACAI). Seventy-seven patients (86.5%) with EF ≥ 50% had DD. Associations with advanced age and comorbid diabetes mellitus and cardiovascular disease were observed. The CAVI, TBI, and ACAI, but not ABI, increased proportionally with DD grades. Thus, many hemodialysis patients developed DD, with systolic function maintained. Strong associations between DD grades and progression of both atherosclerosis and vascular calcification could be inferred.

Loss of Residual Renal Function is Associated With Vascular Calcification in Hemodialysis Patients.

Vascular calcification is common in chronic hemodialysis (HD) patients and can be measured using abdominal aortic calcification (AAC). Loss of residual renal function (RRF) is associated with increased mortality in HD patients. However, the association between loss of RRF and vascular calcification is unknown. The aim of the study was to analyze the association between loss of RRF and VC in HD patients. All chronic HD (HD for more than 3 months) patients of China Medical University Hospital in 2014 were included. AAC scores were measured semi-quantitatively based on later lumbar radiographs. Loss of RRF was defined as urine output less than 200 mL per day. The association between loss of RRF and AAC was analyzed using logistic regression. Four hundred and thirty-eight chronic HD patients with a mean age of 63 ± 12 years were analyzed. The median (interquartile range) AAC score of all patients was 7 (2-13). The AAC score of patients with loss of RRF was 9 (3-22), significantly higher than that of patients with RRF 5 (0-17) (P = 0.004). Loss of RRF, independent of patients' age, diabetes, C-reactive protein, calcium-phosphorus product and vintage of dialysis was associated with higher AAC scores. Loss of RRF was associated with vascular calcification in HD patients.

P-099: Cardiovascular calcifications in hemodialysis patients

Background Cardiovascular calcifications (CVC) are common in among patients undergoing dialysis and are associated increased morbidity and mortality. They are secondary to several factors, especially the disturbances of calcium and phosphorus homeostasis. The aim of our work is to describe the epidemiology of CVC in chronic hemodialysis. Methods It was a descriptive cross-sectional study conducted in the hemodialysis department of the Military Hospital of Tunis compiling all cases with CVC among 61 chronic hemodialysis patients during the period from May to August 2014. Results A total of 61 dialysis individuals were included. Mean age was 55 years, ranging from 16 to 86 years. Thirty eight were males. Hypertension, diabetes mellitus and dyslipidemia were noted respectively in 95 %, 19 % and 23 % of cases. Fifty Two percent of our patients were smoking and 31 % were alcoholics. The initial nephropathy was glomerular, vascular, tubulointerstitial and indeterminate nephropathy in 33 %, 23 %, 13 % and 26 % of all cases. The median time on dialysis was 8.5 years. Biological parameters showed a mean serum calcium at 2, 15mmol/l [1.51-2.27, phosphorus at 1,54mmol/l [0.44 - 2.45], alkaline phosphatase at 131 IU/L [14-710] and PTH at 414pg/mL [36-2417]. CVC were noted in 28% of our patients. Vascular calcifications were present in 16 cases while valvular calcification in only one patient. Fourteen patients present valvular alterations especially at the mitral valves. Conclusions The CVC is a significant risk factor for mortality in chronic renal failure. The correction of risk factors would be a way to prevent these cardiovascular abnormalities in order to reduce morbidity and mortality and to ensure a better quality of life for hemodialysis. Our study confirms the high prevalence of CVC in hemodialysis patients and emphasizes the importance of early diagnosis and proper management of cardiovascular risk factors including calcium phosphate disorders in this population.

Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients

Vascular calcifications (VCs) and fractures are major complications of chronic kidney disease. Hemodialysis patients have a high prevalence of atrial fibrillation (AF) and an increased risk of thromboembolism, which should be prevented with warfarin, a drug potentially causing increased risk of VCs and fractures. Aim of this study is evaluating, in hemodialysis patients with and without AF, the prevalence of VCs and fractures, as well as identifying the associated risk factors. A total of 314 hemodialysis patients were recruited, 101 with documented AF and 213 without AF. Comorbidities, chronic kidney disease mineral and bone disorder blood tests and therapies were collected. Vertebral quantitative morphometry was carried out centrally for the detection of fractures, defined as vertebral body reduction by ≥20%. In the same radiograph, the length of aortic calcification was also measured. Logistic regression models were applied for evaluating the independent predictors of presence of VCs and vertebral fractures. In our population VCs were very common (>85%). Severe VCs (>10cm) were more common in patients with AF (76%) than in patients without (33%). Vertebral fractures were present in 54% of patients. Multivariable analysis showed that AF (OR 5.41, 95% CI 2.30-12.73) and 25(OH) vitamin D <20ng/mL (OR 2.05, 95% CI 1.10-3.83) were independent predictors of VCs. Age (OR 1.04/year, 95% CI 1.01-1.07) and male gender (OR 1.76, 95% CI 1.07-2.90) predicted vertebral fractures. Hemodialysis patients had an elevated prevalence of severe VCs, especially when affected by AF. Low vitamin D levels were strongly associated with severe VCs. Prevalence of vertebral fractures was also remarkably high and associated with older age and male gender.

Effects of Lowering Dialysate Calcium Concentration on Mineral and Bone Disorders in Chronic Hemodialysis Patients: Conversion from 3.0 mEq/L to 2.75 mEq/L.

Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa.

Serum Soluble Klotho Level Is Associated with Abdominal Aortic Calcification in Patients on Maintenance Hemodialysis

Background: Klotho is a single transmembrane protein originally identified as an ‘aging suppressor'. Emerging evidence reveals that soluble Klotho (sKl) in the circulation plays important roles in anti-aging, anti-oxidation, anti-apoptosis and Wnt signaling. However, the role of serum sKl in the vascular calcification in hemodialysis patients is not clear. The aim of this study was to determine the associations of sKl with abdominal aortic calcification in patients on maintenance hemodialysis (MHD). Methods: 129 MHD patients were enrolled prospectively. Serum sKl level was detected by ELISA. Abdominal aortic calcification was measured by abdomen lateral plain radiograph, and the abdominal aorta calcification (AAC) score was calculated. The sKl levels were observed in patients with different degrees of calcification. Logistic regression analysis was used to determine the risk factor of abdominal aortic calcification in MHD patients. The diagnostic value of sKl for abdominal aortic calcification was assessed using receiver operator characteristic (ROC). Results: Abdominal aortic calcification was seen in 87 of 129 patients. The median AAC score was 4.0 (0.00, 11.00) and the median sKl level was 616.29 (378.19, 821.61) pg/ml. Serum sKl levels were inversely associated with AAC. When evaluated as AAC categories (<5, 5-15, >15) with ordinal logistic regression, each SD higher sKl was associated with 37.1% lower odds of AAC severity (proportional odds ratio: 0.629; 95% confidence interval: 0.413-0.959, p = 0.031) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors and uremic risk factors. Multivariate logistic regression analysis showed that serum sKl levels and smoking were independent risk factors for severe AAC. The area under the receiver-operating characteristic curve (AUC) of serum sKl for severe abdominal aortic calcification was 0.746 (0.612-0.880, p = 0.001), sensitivity was 0.885, and specificity was 0.562 for a cutoff value of 265.39 pg/ml. Conclusions: Lower serum sKl levels are independently associated with severe AAC. Serum sKl might have a diagnostic value for the severe AAC in MHD patients.

Serum sclerostin: the missing link in the bone-vessel cross-talk in hemodialysis patients?

We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. Fifty-three MHD patients, aged 53years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1ng/mL increase [95% confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

0345 : Prevalence and risk factors of valvular calcification in hemodialysis patients

Valvular abnormalities frequently occur in patients with chronic kidney failure. This study evaluated the prevalence of heart valve calcification (HVC) in hemodialysis patients and factors associated with it. Medical charts of 111 hemodialysis patients were reviewed retrospectively. Demographic features and laboratory analysis of the patients were systematically recorded. Echocardiographic findings were collected, including ejection fraction, aortic valve calcification (AVC), mitral valve calcification (MVC), and pulmonary artery pressure. Valvular abnormalities were found in 17 patients (15,3%); 7 patients (6.3%) had mitral valve calcification, 7 (6.3%) had aortic valve calcification, and 3 (2.7%) had both mitral and aortic valve calcification. There is a significant difference between patients with and without HVC regarding serum albumin (41g /l vs 43g/l; p=0.04), CRP rate (23mg/l vs 9,3mg/l; p=0.0094), and taking calcium carbonate (15 patients vs 2; p=0.04). Regarding age, sex, the lipid profile, serum calcium, and parathyroid hormone concentrations, there were no significant differences between patients with and without HVC. This study failed to show an association between heart valve calcification in hemodialysis patients and calcium-phosphorus product and parathyroid hormone levels; however, serum albumin level and CRP rate could be regarded as risk factors.

Determinants of coronary artery calcification in maintenance hemodialysis patients.

In addition to the well-known traditional risk factors, uremia-related so-called novel risk factors and medications appear to affect coronary artery calcification in hemodialysis patients. This study was performed to evaluate coronary artery calcification score (CACS) in maintenance hemodialysis (MHD) patients, and to identify significantly related factors. We assessed CACS using Agatston Score by MDCT, sex, age, dialysis vintage, presence of diabetes mellitus, smoking history, presence of ≥100 ml urine volume/day, normalized protein catabolic rate, geriatric nutritional risk index, administration of active vitamin D3, cinacalcet, phosphate binders or antihypertensive agents, and circulation parameters including creatinine, albumin, corrected calcium and phosphate in 207 MHD patients. Coronary artery calcifications were observed in 192 patients (92.8%). In multivariate analysis, CACS showed direct associations with age (p < 0.001), dialysis vintage (p < 0.001) and presence of diabetes mellitus (p < 0.01), and an inverse association only with active vitamin D3 administration (p < 0.001) in MHD patients. Patients with active vitamin D3 showed significantly lower CACS than in those without it (1349.6 ± 1635.0 vs. 2475.6 ± 2646.6 H, p < 0.05). Older age, longer duration of dialysis and diabetes mellitus are risk factors and administration of active vitamin D3 is protective factor for coronary artery calcification in MHD patients.

ACTIVITY OF CHRONIC INFLAMMATION AND ENDOTHELIAL DAMAGE IN PATIENTS WITH CARDIAC VALVE CALCIFICATION IN DIALYSIS–DEPENDENT CHRONIC KIDNEY DISEASE

The purpose of the research was to identify the role of chronic inflammation in mechanisms of cardiac valve calcification (CVC) in patients undergoing chronic hemodialysis (HD) by determining the relation of inflammatory markers with valve calcification and the correlation of the latter with endothelial damage indices.&#x0D; Methods. The research included 94patients undergoing chronic HD (males, 52, age, (46,4±11,2) years, duration of HD, (28,9±32,4) months). Patients with chronic glomerulonephritis (47,9 %) dominated. All subjects underwent echo– cardiographic examination for detection of CVC. The intensity of the inflammatory process was estimated by the serum content of fibrinogen (FG), amount of circulatory immune complexes (CICs), concentration of C–reactive protein (CRP) and middle molecules (MM). The nitric oxide (NO) production was studied on the plasma content of nitrite–anions (NO2–) by spectrophotometric method, the amount of circulating endothelial cells (CECs) in platelet rich plasma under the method (Hladovec J. et al., 1978), modified by (Susla A.B., Mysula I.R., 2011).&#x0D; Results. The CRP, FG, CICs indices in patients with CVC exceeded in those without the calcification by 44,2 (р=0,009), 18,4 (р&lt;0,001) and 17,2 % (р=0,002) accordingly. The dynamic of the MM with wave length of 254 nm (MM/254) and 280 nm (MM/280) had identical direction. For the first time a group of patients with CVC (n=42) had been identified with correlations between CECs and CRP indices (Rs=0,42, р=0,006), FG (Rs=0,31, р=0,043), CICs (Rs=0,55, р&lt;0,001), MM/254 (Rs=0,36, р=0,018), MM/280 (Rs=0,42, р=0,005) as well as between the values of NO2– and CRP (Rs=–0,55, р&lt;0,001), FG (Rs=–0,41, р=0,007), CICs (Rs=–0,41, р=0,008), MM/254 (Rs=–0,38, р=0,014), MM/280 (Rs=–0,34, р=0,029).&#x0D; Conclusions. The valve calcification in HD patients combines with the activation of chronic inflammation, which manifests itself in accumulation of CRP, FG, CICs and MM, and the inflammation markers tightly correlate with endothelial damage and lack of NO

Magnesium retards the progress of the arterial calcifications in hemodialysis patients: a pilot study.

The aim of the study was to evaluate the impact of magnesium (Mg) on the evolution of arterial calcifications in hemodialysis patients. Seventy-two stable hemodialysis patients were randomly allocated to two groups: 36 administered a regimen containing magnesium carbonate plus calcium acetate as a phosphate binder (Mg group), while the rest 36 received calcium acetate alone (Ca group). The presence and the progression of arterial calcifications were evaluated in plain X-rays using a simple vascular calcification score. The duration of the follow-up period was 12 months. Thirty-two patients of the Mg group and 27 of the Ca group completed the study. The mean time average values of the biochemical laboratories did not differ between the two groups, except serum Mg: 2.83 + 0.38 in the Mg group versus 2.52 + 0.27 mg/dl in the Ca group, p = 0.001. In 9/32 (28.12 %) patients of the Mg group and in 12/27 (44.44 %) patients of the Ca group, the arterial calcifications were worsened, p = 0.276. Moreover, in 4/32 (15.6 %) patients of the Mg group and in 0/27 (0 %) patients of the Ca group, they were improved, p = 0.040. The multivariate logistic regression analysis revealed that serum magnesium was an independent predictor for no progression of the arterial calcifications, p = 0.047. Magnesium probably retards the arterial calcifications in hemodialysis patients. Further clinical studies are needed to clarify whether magnesium provides cardiovascular protection to this group of patients.

The cost of ignoring acute kidney injury.

diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 2010; 104: 811–822 12. Westenfeld R, Krueger T, Schlieper G et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis 2012; 59: 186–195 13. Geleijnse JM, Vermeer C, Grobbee DE et al. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr 2004; 134: 3100–3105 14. Fusaro M, Noale M, Viola V et al. Vitamin K Italian (VIKI) Dialysis Study Investigators. Vitamin K, vertebral fractures, vascular calcifications, and mortality: VItamin K Italian (VIKI) dialysis study. J Bone Miner Res 2012; 27: 2271–2278 15. Hayashi M, Takamatsu I, Kanno Y et al. Japanese Calciphylaxis Study Group. A case-control study of calciphylaxis in Japanese end-stage renal disease patients. Nephrol Dial Transplant 2012; 27: 1580–1584 16. Nigwekar SU, Bhan I, Turchin A et al. Statin use and calcific uremic arteriolopathy: a matched case-control study. Am J Nephrol 2013; 37: 325–332 17. Vissers LE, Dalmeijer GW, Boer JM et al. Intake of dietary phylloquinone and menaquinones and risk of stroke. J Am Heart Assoc 2013; 2: e000455 18. Lonn E, Yusuf S, Arnold MJ et al. Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354: 1567–1577 19. Krueger T, Schlieper G, Schurgers L et al. Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol. Nephrol Dial Transplant 2013; doi: 10.1093/ndt/gft459

Serum Osteoprotegerin level and the extent of cardiovascular calcification in haemodialysis patients

Background Cardiovascular disease is the leading cause of death in chronic kidney disease and hemodialysis population. The mechanisms of vascular damage in this population are not fully explained by traditional cardiovascular risk factor. Osteoprotegerin (OPG) has been shown as an independent predictor of mortality in CKD patients and proposed as a potential biomarker for vascular calcification. Methods A total of 80 subjects (60 hemodialysis patients and 20-age and sex matched healthy control) were studied. Vascular and valvular calcification was measured using plain X-ray and transthoracic echocardiography. Circulating OPG was measured in addition to standard clinical biochemical analysis. Results Osteoprotegerin level showed significant difference between hemodialysis (5.4 ± 2.8 pmol/l) and controls (0.96 ± 0.41 pmol/l) P p = 0.003 and overall valvular calcification with p value Conclusion There is strong positive relationship between osteoprotegerin and both vascular and valvular calcification in hemodialysis patients. This positive correlation may open the gate for routine estimation of this agent as a surrogate marker of cardiovascular calcification in hemodialysis patients.

Cardiovascular Calcification in Chronic Hemodialysis Patients: Contributors Interplay

Traditional cardiovascular risk factors are common among chronic kidney disease (CKD) patients. However the high prevalence of atherosclerosis and arterial calcification in CKD is far beyond the explanation by common cardiovascular risk factors. The aim of this study is to determine the incidence of cardiovascular calcification and its relation to demographic data, hemodialysis data and laboratory biomarkers and to evaluate the cardiovascular risk of atherosclerosis in hemodialysis patients. Fourty CKD patients on regular hemodialysis and twenty healthy volunteers were subjected to echocardiography, carotid ultrasound and laboratory studies including serum parathrmone (PTH), 25(OH) vitamin D, feutin and osteoprotegerin levels (OPG). The echocardiographic data showed a statistically significant increase in interventricular septum thickness (IVST), posterior wall thickness (PWT) and left ventricular mass index (LVMI) in patients group compared to the controls. Thirty patients (75%) had valvular calcification. There was significant increase in carotid intima-media thickness (CIMT) in patients group. Serum levels of Ph, PTH and Osteoprotegerin were significantly increased, however, serum levels of Ca, Vitamin D and Feutin were significantly decreased in patients group. Serum level of Ph, and Osteoprotogerin were significantly increased while Vitamin D and feutin were significantly decreased in patients with valvular calcification compared to patients without valvular calcifications. The level of Vitamin D and Fetuin were negatively correlated with creatinine, PTH and osteoprotogerin. While, the level of osteoprotogerin and PTH were positively correlated with creatinine and with each other, they were negatively correlated with HDL-c and eGFR. CIMT was positively correlated with LVMI, PWT, urea, creatinine, CRP, Ca and was negatively correlated with EF%, eGFR, HDL-c, vitamin D and Feutin. We concluded that hemodialysis patients with valvular calcifications were older in age, with a longer hemodialysis duration and showed higher Ph level, Ca x P product and OPG level and lower 25(OH)-vitamin D and fetuin A level. Also, they showed lower EF % and were on lower doses of alphacalcidol and higher doses of calcium compared to patients without valvular calcifications. So, our study points to the importance of administration of active vitamin D derivatives to decrease the risk of valvular calcification and atherosclerosis. Serum fetuin A and osteoprotegerin can be used as a simple, easily performed biomarkers mirroring valvular calcification in hemodialysis patients. Further studies should be done to assess trials for the addition of fetuin A in the treatment of CKD patients to prevent the occurrence of calcification.

Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol

Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients. VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.

FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients

BackgroundDisordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients.MethodsSeventy-four HD patients (36 male/38 female, mean age: 52 ± 14 years) were included. Serum FGF-23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG).ResultsAge, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80–468) vs 147 (82–234), p = 0.04]. Patients were divided into two groups according to baseline CACS (low group, CACS ≤ 30; high group, CACS > 30). Serum FGF-23 levels were significantly correlated with the progression of CACS (ΔCACS) in the low baseline CACS group (r = 0.51, p = 0.006), but this association was not found in high baseline CACS group (r = 0.11, p = 0.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model.ConclusionsSerum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients.