Risk factors associated with valvular calcification in patients with chronic kidney disease. Analysis of NEFRONA study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors. MATERIAL AND METHODS: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months. RESULTS: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR. CONCLUSIONS: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups.

Mineral metabolism factors predict accelerated progression of common carotid intima-media thickness in chronic kidney disease: the NEFRONA study.

BACKGROUND: The leading cause of premature death in chronic kidney disease (CKD) is cardiovascular disease (CVD), but risk assessment in renal patients is challenging. The aim of the study was to analyse the factors that predict accelerated progression of common carotid intima-media thickness (CCIMT) in a CKD cohort after 2 years of follow-up (2010-12). METHODS: The study included 1152 patients from the NEFRONA cohort with CKD stages 3-5D and without a clinical history of CVD. CCIMT was measured at the far wall on both common carotids. CCIMT progression was defined as the change between CCIMT at baseline and at 24 months for each side, averaged and normalized as change per year. Accelerated progressors were defined as those with a CCIMT change ≥75th percentile. RESULTS: The median CCIMT progression rate was 0.0125 mm/year, without significant differences between CKD stages. The cut-off value for defining accelerated progression was 0.0425 mm/year. After adjustment, age was a common factor among all CKD stages. Traditional cardiovascular risk factors, such as diabetes and systolic blood pressure, were predictors of progression in CKD stages 4-5, whereas high-density lipoprotein and low-density lipoprotein cholesterol predicted progression in women in stage 3. Mineral metabolism factors predicting accelerated progression were serum phosphorus in stages 3 and 5D; low 25-hydroxyvitamin D and parathyroid hormone levels >110 pg/mL in stages 4-5 and intact parathyroid hormone levels out of the recommended range in stage 5D. CONCLUSIONS: Mineral metabolism parameters might predict accelerated CCIMT progression from early CKD stages.

Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Serum phosphate has been associated to cardiovascular disease in the general population and this effect seems to be different according to sex. In the present study we analyze the effect of phosphate on subclinical atherosclerosis in the NEFRONA population and its effect depending on sex. DESIGN: Carotid ultrasound assessing the presence of plaques was performed by an itinerant team in 1687 CKD patients not in dialysis without previous cardiovascular events. Standard blood test and anthropometrical parameters were also recorded. RESULTS: Multivariate linear regression to model phosphate levels in patients with CKD showed an interaction of sex with age. Thus, among men, serum phosphate levels declined significantly with age almost linearly. Serum phosphate levels in women under the age of 40-45 years overlapped with those in men and then stayed above, showing and overall constant relationship. Multivariate logistic regression analysis showed that higher phosphate levels associated with a higher risk of presenting atheromatous plaque. This risk however was different according to sex. In men, phosphate levels within the normal range associated with an increased risk of subclinical atheromatosis whereas in women this risk only increased with serum levels over the normal range. CONCLUSIONS: This study demonstrates that phosphate levels are associated with the presence of subclinical atheromatosis in a large CKD population. This effect of phosphate on subclinical atheromatosis was different according to sex, suggesting that a recommended serum phosphate levels could be different for male than for female CKD patients.

Large artery calcification on dialysis patients is located in the intima and related to atherosclerosis.

BACKGROUND AND OBJECTIVES: Vascular calcification (VC) has a significant effect in cardiovascular diseases on dialysis patients. However, VC is assessed with x-ray-based techniques, which do not inform about calcium localization (intima, media, atherosclerosis-related). The aim of this work is to study VC and its related factors using arterial ultrasound to report the exact location of calcium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an observational, cross-sectional, case-control study that included 232 patients in dialysis and 208 age- and sex-matched controls with normal kidney function. Demographic data and laboratory values were collated. Carotid, femoral, and brachial ultrasounds were performed to assess VC and atherosclerosis burden using a standardized protocol. RESULTS: Cardiovascular risk factors were predominantly found in controls, although the burden of atherosclerosis was higher in the dialysis group. VC was significantly more prevalent in the group of patients on dialysis than control subjects, and in both groups the most prevalent pattern of VC was linear calcification located in the intima of the artery wall. Age and undergoing dialysis (with or without previous cardiovascular diseases) were positively and significantly associated with linear calcification. Conversely, the absence of atherosclerosis and low levels of C-reactive protein and phosphorus significantly impeded the development of linear calcification. CONCLUSIONS: VC in large, conduit arteries is more prevalent in patients on dialysis than controls and is predominantly located in a linear fashion in the intima of the arteries.

Effect of a quality improvement strategy on several haemodialysis outcomes.

BACKGROUND: Intermediate outcomes are associated with the survival of long-term haemodialysis patients; however, outcome variability across centres may result in heterogeneous quality of care. The study aim was to evaluate a multifaceted quality improvement activity (QIA) targeting several haemodialysis clinical performance measures. METHODS: A total (prevalent and incident) of 313 patients from four dialysis units were included. The QIA was based on a multifaceted strategy involving collection of haemodialysis clinical performance measures every 6-8 months, feedback about results, improvement plans and benchmarking, and it was tested in a 3-year prospective interventional study. Two timepoints of clinical performance measures were considered for evaluating the QIA: baseline (February 2003, pre-QIA) and final (February 2006, post-QIA). RESULTS: Centres showed significant improvement in percentage of patients with haemoglobin <11 g/dl, mean haemoglobin; percentage of patients with Kt/v <1.2, mean Kt/v; percentage of patients with phosphorous >5.5 mg/dl, mean phosphorous; percentage of patients with calcium phosphate product >55, mean calcium phosphate product; and percentage of patients with ferritin <200 ng/ml, mean ferritin. No change was observed in percentage of patients with haemoglobin between 11 and 13 g/dl, erythropoietin consumed; percentage of patients with ferritin <100 ng/ml; percentage of patients with ferritin >800 ng/ml; percentage of patients with albumin <3.5 g/dl, mean albumin; or percentage of native arteriovenous fistula. The percentage of patients with haemoglobin >13 g/dl was increased. CONCLUSIONS: Quality-improvement strategies can help improve haemodialysis performance for anaemia, dialysis dose and bone metabolism. The importance of assessing patients with high haemoglobin level should be stressed.

Safety and efficacy of sevelamer in the treatment of uncontrolled hyperphosphataemia of haemodialysis patients.

BACKGROUND/AIM: The treatment of hyperphosphataemia is of major importance in the management of patients on dialysis. Traditional phosphate binders can be associated with undesirable effects. Recently, a new non-absorbable phosphate-binding polymer, sevelamer hydrochloride, has been available. Clinical information is scarce, and its cost could be a limiting factor for its wider use. No studies have evaluated its usefulness in uncontrolled hyperphosphataemic patients. METHODS: We identified 34 patients with a maintained serum phosphorus concentration >6.5 mg/dl and/or toxicity related to standard phosphorus-binding treatment (aluminium or calcium based). Sevelamer was added and titrated up fortnightly to achieve phosphorus control. Previous phosphate binders were decreased, whenever possible. The period of the study was 6 months. RESULTS: Thirteen patients (38%) dropped out because of side effects, mainly related to the gastro-intestinal tract. The efficacy analysis disclosed that the phosphorus concentration decreased from 2.39 +/- 0.48 to 1.84 +/- 0.48 mmol/l (p < 0.001). The mean dose of sevelamer was stabilised at 3.4 +/- 1.8 g/day. The amount of calcium- and aluminium-based phosphate binders could be decreased from 5.1 +/- 3.5 to 3.1 +/- 2.7 g/day (38% decrease) and from 2.4 +/- 1.5 to 1.5 +/- 1.7 g/day (36% decrease), respectively. The Ca x P product was significantly decreased from 5.83 +/- 1.19 to 4.36 +/- 1.12 mmol/l2 (p < 0.001). The total cholesterol concentration decreased from 4.34 +/- 0.9 to 3.98 +/- 0.9 mmol/l (p < 0.01) and the low-density lipoprotein cholesterol level from 2.61 +/- 0.98 to 2.20 +/- 0.77 mmol/l (p < 0.03). CONCLUSIONS: Sevelamer is an effective phosphate binder that allows a better serum phosphorus control, while allowing a decrease in the dose of calcium- and aluminium-based phosphate binders in these difficult patients. The drawbacks are the high intolerance rate and the price of the product.