Risk Factors In Dialysis Patients Research Articles

#1853 Comparative analysis of atherosclerotic risk factors in dialysis patients

Abstract Background and Aims Prevailing studies indicate a correlation between elevated serum phosphate levels and an augmented incidence of cardiovascular events. In patients undergoing dialysis, hyperphosphatemia contributes to vascular and valvular calcifications. This study analyzes the interrelation of phosphate levels, inflammatory markers, and additional risk determinants in the development of carotid artery atherosclerosis in individuals receiving peritoneal dialysis (PD) versus hemodialysis (HD). Method A cohort of 39 PD and 53 HD patients were recruited, all undergoing stable renal replacement therapy (RRT) for three to thirty-six months. B-mode ultrasonography assessed the carotid artery intima-media thickness (CIMT) and detected plaque and calcification occurrences. Patients were specified as having atherosclerosis when CIMT was greater than 1 cm, and the presence of plaque was identified. Logistic regression analysis was employed to discern the connection between potential risk factors and the incidence of atherosclerosis. Results The study encompassed 92 participants, 61% undergoing HD and an average age of 53.4 years (standard deviation ± 14.5 years). The tubulo-interstitial disease was the predominant initial pathology, followed by chronic glomerulonephritis and nephroangiosclerosis. Diabetic nephropathy was identified as the etiology of end-stage renal disease (ESRD) in 23.1% of PD and 11.4% of HD subjects (p = 0.047). Notably, PD patients showed better residual renal function (RRF) (p < 0.001), urine volume over 24 hours (p < 0.001), and C-reactive protein (CRP) (p = 0.047), alongside diminished phosphate (p = 0.01), parathyroid hormone (PTH) (p < 0.05), alkaline phosphatase (p < 0.05), and albumin levels (p < 0.001) relative to their HD counterparts. Atherosclerosis prevalence was 66.3%, inclusive of the entire diabetic cohort. The incidence of atherosclerosis did not significantly diverge between PD and HD groups [56.4% vs 73.6% in HD, respectively]. Atherosclerotic patients were older (p < 0.001) and exhibited heightened phosphate levels (p = 0.012), pulse pressure (p = 0.01), and calcium index (Ci) (p = 0.034). Multiple regression analysis elucidated age, phosphate, RRF, PTH, pulse pressure, diabetes, and HD modality as autonomous factors linked to atherosclerosis. Conclusion Beyond conventional risk factors like age and diabetes, metabolic disorders arising from renal insufficiency were identified as contributing to atherosclerotic development. Multivariate analysis identified phosphate, RRF, and pulse pressure (PP) as independent atherosclerotic risk factors. The HD modality carried an elevated atherosclerotic risk compared to PD. It was thought that preserving RRF in PD patients would improve phosphate regulation and maybe even improve endothelial function, explaining the differences found.

Reduced phosphorus is associated with older age and hypoalbuminemia. Risk factors for all-cause mortality in peritoneal dialysis patients.

Hyperphosphatemia is a mortality risk factor in dialysis patients; however, low phosphorus levels too. Diabetes and malnutrition are strongly associated with mortality and with reduced serum phosphorus. This study analyzed the pattern of serum phosphorus in patients on Peritoneal Dialysis (PD) and its association with mortality. A Secondary analysis was performed on a multicenter cohort study in peritoneal dialysis patients from two previous studies done by our group. Six hundred fifty-four patients were included. Serum phosphorus was <3.6 mg/dL in 28.29% of patients, 3.6 to 5.2 mg/dL in 48.16%, and >5.2 mg/dL in 23.55%. In logistic regression analysis; education, age, and hypoalbuminemia were risk factors for low P levels. In multivariate Cox analysis P < 3.6 mg/dL, age, and low albumin were predictors for all-cause mortality. When lower P and lower albumin were combined, this group had the highest risk for all cause and cardiovascular mortality. The frequency of patients with reduced serum phosphorus was higher in the Mexican population than in Europe or Asia. Low serum phosphorus levels, older age and hypoalbuminemia were risk factors for all-cause mortality. Low phosphorus combined with low albumin levels were the highest risk factor for all-cause and cardiovascular mortality.

Toxin Removal and Inflammatory State Modulation during Online Hemodiafiltration Using Two Different Dialyzers (TRIAD2 Study).

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.

Cancer incidence and risk factors in dialysis patients with human immunodeficiency virus: a cohort study.

BackgroundPatients with human immunodeficiency virus (HIV) or end-stage renal disease receiving dialysis have an increased risk of developing malignancies, but few data are available on cancer in patients with both conditions. Thus, the objective of this study was to determine the incidence of selected malignancies and identify their potential risk factors in HIV-infected dialysis patients.MethodsThis study was a nationwide cohort analysis using the US Renal Data System. Participants included all HIV-infected patients starting dialysis from 2005 to 2011. HIV status, comorbidities and malignancies were identified using International Classification of Diseases, Ninth Revision codes. Descriptive statistics and generalized linear models quantifying risk factors were performed for the overall cohort and the three most common malignancies.ResultsOverall, 6641 HIV-infected dialysis patients were identified, with 543 (8.2%) carrying a malignancy diagnosis. The most common malignancies were non-Hodgkin’s lymphoma (NHL, 25%), Kaposi sarcoma (KS, 16%) and colorectal cancer (13%). Factors increasing the risk of any malignancy diagnosis included: history of cancer [adjusted relative risk (aRR) = 5.37], two or more acquired immunodeficiency syndrome-defining opportunistic infections (ADOIs) (aRR = 3.11), one ADOI (aRR = 2.23), cirrhosis (aRR = 2.20), male sex (aRR = 1.54) and hepatitis B (aRR = 1.52). For NHL and colorectal cancer, history of cancer (aRR = 7.05 and 9.80, respectively) was the most significant risk factor. For KS, two or more ADOIs (aRR = 6.78) was the largest risk factor.ConclusionsOver 8% of HIV-infected dialysis patients developed a malignancy. History of cancer and ADOIs were major risk factors, underscoring the significance of immune dysregulation in malignancy development.

Clinical Profile and Outcome of Intracranial Bleeding in Patients Undergoing Hemodialysis at a Tertiary Hospital

Background: Stroke is one of the leading causes of mortality in the dialysis population. Although there is plenty of literature available for cardiovascular risk factors in dialysis patients, very few studies have focused on cerebrovascular events and Indian data are sparse. Objectives: This study was undertaken to address some of these shortcomings. Methods: This is a matched cohort study. There were 30 cases with intracranial bleeding (ICB) in hemodialysis patients whose clinical profiles were compared with 60 matched controls with no ICB and the data was analyzed. Results: The common cause of chronic kidney disease (CKD) was diabetes. Event BP was high but not significantly. Serum albumin values were lower in patients than in controls (2.65 vs. 3.15 g/dL). The common site of bleeding in our study was intraparenchymal (60%), followed by subdural hematoma (30%). Mortality was 76.7% in one month. Although the incidence of bleeding was slightly more in the thrice-weekly dialysis group, the difference was not significant. The diabetic status of ICB patients was poorly controlled. Conclusions: Hemodialysis patients have multiple risk factors for ICB and low serum albumin could be one of them. These patients have high short-term mortality (76.7%). There was a slightly increased incidence of ICB in patients who underwent thrice-weekly dialysis and those with poor glycemic control. This needs a systemic study with larger sample size and longer follow-up.

Cumulative Exposure to Frequent Intradialytic Hypotension Associates With New-Onset Dementia Among Elderly Hemodialysis Patients

Cumulative Exposure to Frequent Intradialytic Hypotension Associates With New-Onset Dementia Among Elderly Hemodialysis Patients

Osteocalcin and carotid-femoral pulse wave velocity in patients on peritoneal dialysis.

Objective:Vascular calcification is a cardiovascular risk factor in dialysis patients. Vascular calcification involves a complex process of biomineralization resembling osteogenesis, which leads to arterial stiffness. Osteocalcin is the most abundant noncollagenous protein in the bone matrix. It is synthesized in the bone by osteoblasts and reflects the rate of bone formation. The aim of this study was to evaluate the relationship between serum osteocalcin levels and the carotid–femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients.Materials and Methods:Serum intact osteocalcin and cfPWV were measured in 62 PD patients. Those with CfPWV values >10 m/s were defined as the high central arterial stiffness group, while those with values ≤10 m/s were regarded as the low central arterial stiffness group, according to the European Society of Hypertension and of the European Society of Cardiology guidelines.Results:Seventeen of the 62 PD patients (27.4%) were in the high central arterial stiffness group. The high central arterial stiffness group were older (P = 0.002), had a longer PD vintage (P = 0.018), and had higher serum osteocalcin levels (P = 0.001) than those in the low group. Multivariate logistic regression analysis showed that the osteocalcin level (odds ratio: 1.069, 95% confidence interval (CI): 1.005–1.137, P = 0.035), PD vintage (odds ratio: 1.028, 95% CI: 1.010–1.048, P = 0.003), and age (odds ratio: 1.081, 95% CI: 1.005–1.162, P = 0.035) were independently associated with central arterial stiffness in PD patients. Among these patients, cfPWV (β: 0.216, P = 0.001) values and log-transformed intact parathyroid hormone (β: −’0.447, P < 0.001) levels were independently associated with the osteocalcin level in PD patients after multivariate forward stepwise linear regression analysis.Conclusion:Older PD patients with a longer PD vintage and higher serum osteocalcin levels had higher central arterial stiffness as measured by cfPWV. The serum osteocalcin level is an independent marker of central arterial stiffness in PD patients.

Mortality and Associated Risk Factors in Dialysis Patients with Cardiovascular Disease

Background/Aims: Although dialysis patients have a higher risk of morbidity and mortality related to cardiovascular disease (CVD) than the general population, the mortality and associated risk factors in Asian dialysis patients with CVD have not been well examined. Methods: In this prospective cohort study, mortality and risk factors were investigated in 591 dialysis patients who were recruited from two dialysis centers from May 1, 2009 to May 1, 2014. The Cox proportional hazards regression assessed adjusted differences in mortality risk. A multivariate analysis was also performed, comparing the CVD and non-CVD groups. Results: A total of 591 patients were enrolled in this study (mean age, 52.05 ± 16.46 years [SD]; 61.8% men; 20.8% with CVD), with a median follow-up of 21.9 (maximum, 72) months. The cumulative hazard of mortality was significantly higher in CVD patients (hazard ratio [HR], 1.835; 95% confidence interval [CI], 1.023-3.293; P=0.042) than in their non-CVD counterparts after adjusting for various confounders. On multivariate Cox analysis, stroke (HR, 4.574; 95% CI, 2.149-9.736; P<0.001) was an independent predictor of all-cause mortality in the CVD group. In the non-CVD group, diabetes mellitus (HR, 2.974; 95% CI, 1.560-5.668; P=0.001) and elevated high-sensitivity C-reactive lipoprotein (hs-CRP) (HR, 1.017; 95% CI, 1.005-1.030; P=0.005) were independent predictors of all-cause mortality. Conclusion: All-cause mortality was significantly higher in the CVD group than in the non-CVD group. Stroke is an independent risk factor for all-cause mortality in dialysis patients with CVD. These findings warrant further studies into preventive and interventional strategies.

New reliable methods for the diagnose of protein-energy wasting in hemodialysis patients

Protein-energy wasting (PEW), defined as the body loss of muscle mass and fat, is an important cardiovascular risk factor in dialysis patients. Diagnosing this condition requires the presence of three characteristics: biochemical (low albumine, prealbumine or cholesterol), body mass reduction (body mass index, weight loss or fat loss) and muscle mass reduction (measured by means of creatinine or arm muscle area). This study aimed at demonstrating that the lean tissue index (LTI) calculated by spectroscopic bioimpedance (SBI) is a valid parameter for the diagnostic of protein-energy wasting. Cross-sectional study including 1369 patients with two BCM measurements on a six-month delay, analyzing analytic and spectroscopic bioimpedance parameters. The lean tissue index from the BCM (Body Composition Monitor) quantifies the patient's lean mass and it is matched against traditional parameters (plasma albumine) and non-traditional parameters (IRE and PCR) for protein-energy wasting with no alterations from the patient's hydration level. LTI is an easy to obtain parameter of lean mass which can be followed and monitored in order to diagnose risk situations of our patients as it is the protein- energy wasting.

Ionizing radiation exposure: another underrecognized risk factor for poor health outcomes in dialysis patients

Dialysis patients are at greater risk for cancers, cardiovascular disease, and all-cause mortality than people in the general population. Novel risk factors have been identified that may help explain these risk elevations. We discuss medical radiation exposure as a novel risk factor in dialysis patients and suggest the need for future research on this topic.

Endotoxemia is Associated with Better Clinical Outcome in Incident Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study

Endotoxemia is common in peritoneal dialysis (PD) patients; circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We examine whether baseline plasma LPS level represents a prognostic marker in new PD patients. We studied 158 new Chinese PD patients (80 males). Baseline plasma LPS level at initiation of PD was measured. Patients were stratified into quartiles according to plasma LPS level: quartile I, <0.45 EU/mL; II, 0.45 - <0.70 EU/mL; III, 0.70 - <0.95 EU/mL; and IV, ≥ 0.95 EU/mL. The patients were then prospectively followed for the development of cardiovascular events. All-cause mortality and duration of hospitalization were also recorded. Average age was 55.6 +/- 14.7 years; average endotoxin concentration was 0.70 +/- 0.30 EU/mL; average follow-up was 55.5 +/- 36.9 months. At 60 months, event-free survival was 41.0%, 52.5%, 65.0%, and 61.5% for LPS level quartiles I, II, III, and IV, respectively (log rank test p = 0.066). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, plasma LPS level had no independent effect. At 60 months, technique survival was 20.5%, 20.0%, 32.5%, and 51.3% for LPS level quartiles I, II, III, and IV, respectively (log rank test p = 0.0009). By Cox proportional hazard model, each higher quartile of LPS conferred 28.6% protection (95% confidence interval 15.6% - 40.3%, p = 0.0002) from developing technique failure. A higher plasma LPS level had a lower all-cause mortality (unadjusted hazard ratio 0.486, p = 0.046) and cardiovascular mortality (unadjusted hazard ratio 0.251, p = 0.025), but the result became insignificant after adjusting for potential confounders. A higher baseline plasma LPS level is an independent predictor of better technique survival in new Chinese PD patients, with an insignificant trend of fewer cardiovascular events. The observation seems to conform to the phenomenon of reverse epidemiology for other traditional cardiovascular risk factors in dialysis patients but the exact reason for this paradoxical phenomenon requires further investigation.

Is Lipid Control Necessary in Hemodialysis Patients?

Although high serum total cholesterol and LDL cholesterol levels are predictive of cardiovascular diseases in the general population, this association is more complex in the dialysis patients. Two recent randomized trials failed to show significant beneficial effects of statins on the primary cardiovascular outcomes in these patients. The reasons for this lack of benefits are unclear. The postulates include the possibilities that LDL cholesterol is not important in atherogenesis and that atherosclerosis is not a major contributor to cardiovascular diseases in the dialysis population. It is important to note that high serum LDL cholesterol level is not a prominent feature of uremic dyslipidemia. Instead, the hallmark dyslipidemias in the dialysis population are hypertriglyceridemia as a result of the accumulation of lipoprotein remnant particles, low serum HDL cholesterol levels, high serum levels of lipoprotein(a) [Lp(a)], and the modification of LDL cholesterol by oxidation and carbamylation. In vitro and epidemiologic studies have further suggested that these abnormal lipoproteins or aberrant serum lipoprotein levels are atherogenic. More research efforts should be directed toward these dyslipidemic states and the multitude of other putative cardiovascular risk factors in dialysis patients.

Risk Factors of Normal Ankle–Brachial Index and Low Toe–Brachial Index in Hemodialysis Patients

The prevalence of peripheral arterial occlusive disease is high in patients with terminal renal failure, and it is a major problem in those on dialysis. A low ankle-brachial index (ABI) suggests the presence of arterial stenotic lesions between the aorta and the ankle joint, while a low toe-brachial index (TBI) suggests stenotic lesions between the aorta and the toes. Therefore, a normal ABI (> or =0.9) and a low TBI (<0.6) may indicate the presence of stenotic lesions located only on the peripheral side of the ankle joint. In the present study, risk factors of normal ABI/low TBI were investigated. In 115 patients on maintenance dialysis, the ABI and TBI were simultaneously measured, and the background factors and laboratory data of patients with normal ABI/low TBI (L group) and those with normal ABI/normal TBI (> or =0.6) (N group) were compared. Low ankle-brachial and toe-brachial indices were detected in 13% and 22% of the patients, respectively. Comparison of the background factors and laboratory data between the N and L groups showed that the ratio of diabetes mellitus, interdialytic body weight gain, and Hb(A1c) values were significantly higher in the L group than in the N group. It was clarified that diabetes and excess body weight gain are involved as risk factors in dialysis patients with normal ABI/low TBI.

Carotid atherosclerosis and cardiovascular risk factors in hemodialysis and peritoneal dialysis patients

Background: Cardiovascular diseases are important factors in mortality and morbidity of dialysis patients. Cardiovascular risk assessment is important in order to arrange the treatment strategies. The aim of the study was to investigate the relationship between carotid atherosclerosis and various CVD risk factors in dialysis patients. Methods: 22 HD and 54 PD patients were included in the study. Carotid artery intima media thickness (IMT) and plaque score (PS) were obtained by B-mode ultrasonography for each participant. Uric acid, albumin, bilirubin, lipid profile, apolipoprotein A-l (apo A-l), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], high-sensitivity CRP (hs-CRP), homocysteine (Hcy), vitamin A, vitamin E, sialic acid (SA) and thiobarbituric acid-reactive substances (TBARS) were determined. The differences of the cardiovascular risk factors between the patients according to the treatment modality and the comparison of the risk factors as indicators of IMT and PS were investigated. Results: There was no significant difference in IMT and PS between the two groups. SA, TBARS, hs-CRP, total, HDL- and LDL-cholesterol, white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels were significantly higher; albumin levels were significantly lower in PD group. In multiple regression analysis, only bilirubin for IMT and SA for PS were independent predictors. Conclusions: SA can be a superior marker to hs-CRP in PD patients; however, hs-CRP seems to be a more valuable marker than SA in HD patients according to the correlation analysis. This study provides information and opportunity for comparison of relatively new cardiovascular risk markers in hemodialysis and peritoneal dialysis patients using carotid atherosclerosis as an objective assessment criterion.

Serum Troponin T Concentration as a Predictor of Mortality in Hemodialysis and Peritoneal Dialysis Patients

Troponin T is a good predictor of all-cause and cardiovascular mortality in cardiac patients. Although it is known that troponin T is an independent risk factor in dialysis patients as well, its prognostic value when measured routinely in clinical practice, particularly in addition to other risk indicators, is unclear. A cohort of 847 patients who started dialysis therapy between 1997 and 2001 and participated in a multicenter follow-up study was examined. Clinical data were determined 3 months after the start of dialysis therapy. Patients were followed up until date of death or censoring in November 2003. For patients with troponin T values of 0.05 to 0.10 microg/L, hazard ratio for all-cause mortality was 2.2 (95% confidence interval [CI], 1.7 to 2.8) compared with patients with values less than 0.05 microg/L. For patients with values greater than 0.10 microg/L (11%), hazard ratio was 3.3 (95% CI, 2.5 to 4.5). A survival model with clinical and laboratory risk indicators yielded an area under the curve of 0.81, which did not increase when troponin T level was added to the model. The area under the curve for troponin T level alone was 0.67. No important differences were found between patients on hemodialysis or peritoneal dialysis therapy and between patients with high and low residual renal function. Although troponin T level is an independent risk factor for mortality in dialysis patients, it has limited added predictive power as a routine screening test over other clinical risk factors in dialysis patients.

Septicemia, access and cardiovascular disease in dialysis patients: The USRDS Wave 2 Study

Microinflammation is linked to cardiovascular disease, and is highly prevalent in dialysis patients. It is logical to postulate that septicemia, a common macroinflammatory occurrence in dialysis patients, contributes to their large burden of cardiovascular disease. The Dialysis Morbidity and Mortality Wave 2 was a randomly selected prospective cohort of incident dialysis patients. Admission claims data were used to define and calculate rates of septicemia or bacteremia and cardiovascular events in those with Medicare as the primary payer. Utilizing Cox proportional hazard models we determined the association between baseline access and the development of bacteremia or sepsis, and also the association between bacteremia or sepsis episodes and subsequent cardiovascular events. The 2358 (59%) patients with Medicare as primary payer were older and more likely to have heart failure than those with other payers, but had similar comorbidity-adjusted mortality hazards. Rates of first septicemia, bacteremia, or either condition, were 7.0, 5.9 and 10.4 events per 100-patient years, respectively. Cox regression identified initial dialysis access as the main antecedent of septicemia or bacteremia. Hazards ratios for hemodialysis with permanent catheters, temporary catheters, and grafts were 1.95 (95% CI 1.47-2.57), 1.76 (95% CI 1.29-2.41), and 1.05 (95% CI 0.82-1.35), respectively, while that for peritoneal dialysis was 0.96 (95% CI 0.75-1.23) (reference arteriovenous fistula). After adjustment for baseline factors, septicemia or bacteremia, as a time-dependent covariate, was associated with subsequent death [hazards ratio (HR) 2.33, 95% CI 1.38-2.28], myocardial infarction (HR 1.78, 95% CI 1.38-2.28), heart failure (HR 1.64, 95% CI 1.39-1.95), peripheral vascular disease (HR 1.64, 95% CI 1.34-2.0), and stroke (HR 2.04, 95% CI 1.27-3.28). Septicemia appears to be an important, potentially preventable, cardiovascular risk factor in dialysis patients.

Fetuin-A and extraosseous calcification in uremia

It has become increasingly clear that vascular calcification, as part of accelerated uremic atherosclerosis, may powerfully predict mortality in the dialysis population. Secondary hyperparathyroidism and its consequences explain part of this phenomenon; however, serum concentrations of calcium and phosphate ions exceed their solubility product in an aqueous solution and must be prevented from precipitation by additional mechanisms. Fetuin-A is an inflammation-related calcium-regulatory glycoprotein acting as a systemic calcification inhibitor. The emerging role of fetuin-A deficiency as a risk factor in dialysis patients was documented in a cross-sectional study demonstrating a significant correlation with all-cause and cardiovascular mortality. In-vitro studies in vascular smooth muscle cells revealed that fetuin-A interacts directly with matrix vesicle release and may thus modulate vascular calcification processes locally and at early stages. Accordingly, prominent fetuin-A staining of calcified vessel segments obtained from uremic patients, in the absence of local expression, emphasizes its potential role as a circulating defense against overwhelming calcification. While increased fetuin-A levels positively correlated with vascular calcification in patients with diabetes and mild to moderate renal impairment, an inverse relationship was observed in dialysis patients. Both chronic inflammation and uremia may thus contribute to exhausting fetuin-A release in the late stages of kidney disease. Specific polymorphisms of the fetuin-A gene may be additional determinants of fetuin-A deficiency. Deficiencies of calcification inhibitors such as fetuin-A are relevant pathomechanisms in the progression of uncontrolled vascular calcification and may offer potential for future therapeutic approaches.

Prognostic value of combined use of biomarkers of inflammation, endothelial dysfunction, and myocardiopathy in patients with ESRD

Cardiovascular risk stratification is important in the clinical management of patients with end-stage renal diseases (ESRD) and biomarkers are increasingly used in these patients. In a cohort of 246 dialysis patients without heart failure at baseline we tested the combined prognostic power of three well-established biomarkers: brain natriuretic peptide (BNP), C-reactive protein (CRP), and asymmetric dimethyl arginine (ADMA). The independent prognostic value of individual and combined biomarkers was estimated in separate Cox models, including standard risk factors in dialysis patients and comorbidities. When the prediction power of the three biomarkers was evaluated individually, BNP, ADMA, and CRP added significant predictive value (P< or = 0.01) to all-cause and cardiovascular mortality models and the explanatory gain attributable to these biomarkers were of similar degree (ranging from 3.3% to 5.7%). When the biomarkers were evaluated jointly, a score based on the BNP-CRP combination, increased by 9.9% (all-cause) and by 10.5% (cardiovascular) the explained mortality variance of standard Cox models and such gain in power was similar to that achieved by the CRP-ADMA combination (all-cause death 9.0% and cardiovascular death 8.4%). Of note, the explanatory gain derived by the simultaneous use of the three biomarkers was very similar (all-cause death 11.6% and cardiovascular death 10.5%) to that achieved by the use of two biomarkers. These findings indicate a potential role for CRP, BNP, and ADMA to be incorporated into diagnostic and therapeutic strategies aimed at detection and treatment of atherosclerotic complications and at preventing heart failure in the dialysis population.

Nutrition interventions to address cardiovascular outcomes in chronic kidney disease

Nutrition interventions to address cardiovascular outcomes in chronic kidney disease

Inadequate Treatment of Cardiovascular Disease and Cardiovascular Disease Risk Factors in Dialysis Patients: A Commentary

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Despite its significant impact on health outcomes, which would imply a need for aggressive intervention, both CVD and CVD risk factors are inadequately treated in this patient population. The reasons for this inadequate treatment are unclear. This article reviews the contribution of traditional risk factors to the burden of CVD in ESRD patients, outlines the evidence regarding undertreatment of CVD and traditional CVD risk factors, and identifies potential factors that may be responsible for inadequate cardiovascular care in ESRD patients.