Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study

Calcification complications are frequent among long-term dialysis patients. However, the prognostic implication of cardiac valve calcification in this population is not known. This study aimed to determine if cardiac valve calcification predicts mortality in long-term dialysis patients. Baseline echocardiography was performed in 192 patients (mean +/- SD age, 55 +/- 12 yr) on continuous ambulatory peritoneal dialysis (mean +/- SD duration of dialysis, 39 +/- 31 mo) to screen for calcification of the aortic valve, mitral valve, or both. Valvular calcification was present in 62 patients. During the mean follow-up of 17.9 mo (range, 0.6 to 33.9 mo), 46 deaths (50% of cardiovascular causes) were observed. Overall 1-yr survival was 70% and 93% for patients with and without valvular calcification (P < 0.0001, log-rank test). Cardiovascular mortality was 22% and 3% for patients with and without valvular calcification (P < 0.0001). Multivariable Cox regression analysis showed that cardiac valve calcification was predictive of an increased all-cause mortality (hazard ratio [HR], 2.50; 95% CI, 1.32 to 4.76; P = 0.005) and cardiovascular death (HR 5.39; 95% CI, 2.16 to 13.48; P = 0.0003) independent of age, male gender, dialysis duration, C-reactive protein, diabetes, and atherosclerotic vascular disease. Eighty-nine percent of patients with both valvular calcification and atherosclerotic vascular disease, 23% of patients with valvular calcification only, 21% of patients with atherosclerotic vascular disease only, and 13% of patients with neither complication died at 1-yr (P < 0.0005). The cardiovascular death rate was 85% for patients with both complications, 13% for patients with valvular calcification only, 14% for patients with atherosclerotic vascular disease only, and 5% for those with neither complication (P < 0.0005). The number of calcified valves was associated with all-cause mortality (P < 0.0005) and cardiovascular death (P < 0.0005). One-year all-cause mortality was 57% for patients with both aortic and mitral valves calcified, 40% for those with either valve calcified, and 15% for those with neither valve calcified. In conclusion, cardiac valve calcification is a powerful predictor for mortality and cardiovascular deaths in long-term dialysis patients. Valvular calcification by itself has similar prognostic importance as the presence of atherosclerotic vascular disease. Its coexistence with other atherosclerotic complications indicates more severe disease and has the worst outcome.     

Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes

Current literature suggests associations between abnormal mineral metabolism (MM) to cardiovascular disease in dialysis populations, with conflicting results. MM physiology is complex; therefore, it was hypothesized that constellations of MM parameters, reflecting this complexity, would be predictive of mortality and that this effect would be modified by dialysis duration (DD). Prevalent dialysis patients in British Columbia, Canada, who had measurements of calcium (Ca), phosphate (Pi), and parathyroid hormone (iPTH) between January and March 2000 were followed prospectively until December 2002. Statistical analysis included Cox proportional hazard models with Ca, Pi, and iPTH alone and in combination as explanatory variables; analyses were stratified by DD. The 515 patients included in this analysis represent British Columbia and Canadian dialysis populations: 69% were on hemodialysis, mean age was 60 +/- 17 yr, 40% were female, and 34% had diabetes. Mean Ca and Pi values were 2.32 +/- 0.22 mmol/L and 1.68 +/- 0.59 mmol/L, respectively, and median iPTH was 15.8 pmol/L (25th to 75th percentile: 6.9 to 37.3 pmol/L). Serum Pi, after adjusting for demographic, dialysis type and adequacy, hemoglobin, and albumin, independently predicted mortality (risk ratio [RR], 1.56 per 1 mmol/L; 95% confidence interval [CI], 1.15 to 2.12; P = 0.004). When combinations of parameters were modeled (overall P = 0.003), the combinations of high serum Pi and Ca with high iPTH (RR, 3.71; 95% CI, 1.53 to 9.03; P = 0.004) and low iPTH (RR, 4.30; 95% CI, 2.01 to 9.22; P < 0.001) had highest risks for mortality as compared with the combination of high iPTH with normal serum Ca and Pi that had the lowest mortality and was used as index category. These effects varied across different strata of DD. This analysis demonstrates the importance of examining combinations of MM parameters as opposed to single variables alone and the effect of DD. In so doing, the complex interaction of time and MM can begin to be understand. Further exploration is required.     

Differences in bone turnover and intact PTH levels between African American and Caucasian patients with end-stage renal disease

BACKGROUND: Evidence derived from healthy subjects suggests that African Americans have higher serum parathyroid hormone (PTH) levels and decreased bone responsiveness to PTH than Caucasians. African American patients with end-stage renal disease (ESRD) also have higher serum PTH than Caucasians. Studies that correlate intact PTH (iPTH) levels with bone turnover in ESRD patients were performed in a predominantly Caucasian population. METHODS: In this study, serum iPTH and bone histomorphometric data were analyzed for racial differences in 76 ESRD patients (Caucasian = 48, African Americans = 28). Bone turnover was determined by histomorphometric measurement of activation frequency in all patients. RESULTS: Age, duration of dialysis, and calcium and phosphorus levels were similar between the two groups. iPTH levels (pg/mL; mean +/- SE) were significantly higher in the African American group (534 +/- 79 vs. 270 +/- 46, P < 0.01). Also, alkaline phosphatase levels (IU/L) were significantly higher in the African American group (162 +/- 31 vs. 144 +/- 43, P < 0.01). Correlations between PTH levels and activation frequency were r = 0.60, P < 0.01 in Caucasians and r = 0.22, P = NS in African Americans. The mean PTH level in African American patients with histologic findings of low bone turnover was 460 +/- 115 vs. 168 +/- 41 in Caucasian patients with similar bone turnover (P < 0.01). In patients with low bone turnover, African Americans had significantly higher osteoid volume and thickness, number of osteoblasts and osteoclasts, erosion surface, peritrabecular fibrosis, and single-label surface than Caucasians. However, erosion depth, bone formation rate per osteoblast and mineralization apposition rate were similar between the two groups. CONCLUSION: There is no correlation between iPTH and bone turnover in African Americans with ESRD. A substantial number of African American patients with low bone turnover have very high serum PTH levels. Bone histomorphometric results reveal differences in remodeling dynamics and responses to PTH between African American and Caucasian patients. Further studies utilizing newer PTH measurement assays are needed to better delineate the correlation between PTH and bone turnover in the various racial groups.     

Vascular function in patients with end-stage renal disease and/or coronary artery disease: a cardiac magnetic resonance imaging study

Decreased arterial compliance in end-stage renal disease (ESRD) is associated with increased cardiovascular risk. Our aim was to examine aortic compliance in patients with ESRD using cardiac magnetic resonance imaging (MRI) and to compare these with patients with advanced atherosclerotic disease who are known to be at high cardiovascular risk. We examined a total of 83 subjects matched for age: 24 had ESRD and were on dialysis therapy for 3+/-6 years, 24 had severe coronary artery disease (CAD), 11 had both ESRD and CAD (4+/-5 years on dialysis therapy), and 24 healthy subjects with no evidence of CAD. Vascular and cardiac function was assessed using cardiac MRI. Aortic compliance was significantly reduced in patients with CAD compared to control subjects (11.3+/-6.3 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml x 10(-3)/mm Hg, P=0.009). Patients with ESRD also exhibited significantly reduced aortic compliance compared to healthy controls (12.4+/-5.8 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml 10(-3)/mm Hg, P=0.012), whereas there was no significant difference in aortic compliance between patients with CAD and ESRD. Even in the absence of symptomatic CAD, patients with ESRD have significantly reduced aortic compliance compared to normal subjects. Patients with ESRD have equivalent aortic compliance to patients with advanced CAD. These findings suggest that a significantly reduced aortic compliance is one of many mechanisms promoting premature cardiovascular events in patients with ESRD compared to age-matched controls from the general population.     

Activity of systemic lupus erythematosus in end-stage renal disease patients: study in a Brazilian cohort

BACKGROUND: Dialysis has been associated with lupus remission. We studied the prevalence of systemic lupus erythematosus (SLE) as a cause of end-stage renal disease (ESRD) in the metropolitan area of Rio de Janeiro and assessed disease activity in SLE patients on dialysis. METHODS: Of 3,535 ESRD patients, 63 had SLE (1.8%). Fifty-seven entered the study (54 females, 3 males, 38 +/- 10 years). Hemodialysis consisted of 3 sessions per week of about 4 h duration, blood flow of about 400 ml/min, bicarbonate dialysate ([Ca(2+)] = 2.5-3.5 mEq/l) at 500 ml/min and cellulose acetate or polysulfone dialyzers. Activity was initially defined as: non-renal (nr) SLE disease activity index (SLEDAI) of >0; use of at least 20 mg/day of prednisone; and/or any dose of another activity-controlling drug. Fifty-seven ESRD patients without SLE were used as controls. RESULTS: Eighteen SLE patients were under drug treatment; of the remaining, 30 had an nrSLEDAI of >0 totaling 48 patients (84%) initially labeled as active. An apparent activity was also present in 21 controls (37%). Of those, 19 had an nrSLEDAI of <4. With a cutoff of >or=4, figures in each group would be 49 and 4%. Under this criterion, age was the only significant predictor of flare in our SLE ESRD population in a multivariate logistic regression model. Activity remained high in patients who were on dialysis for >5 years (7/18, 39%). CONCLUSION: SLE accounted for 1.8% of our ESRD patients. Application of SLEDAI to dialysis patients may require consideration of confounding factors related to the ESRD state. Even with a score of >or=4 as a cutoff, SLE activity in dialysis patients was high (49%) and long-lasting. Age was the major determinant of flare.     

Detection of cardiac calcinosis in hemodialysis patients by whole-body scintigraphy with 99m-technetium methylene diphosphonate

A noninvasive method for the diagnosis of cardiac calcinosis, a life-threatening complication in hemodialysis patients with end-stage renal disease (ESRD), has not, as yet, been firmly established. We tested whether whole body scanning with 99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis. In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females, aged 40-81, mean 63 +/- 8 years) with cardiovascular disease [mitral annular calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects, respectively, but was absent in controls. Positive cardiac uptake was related to cardiac calcified complications (mobile intracardiac calcinosis, myocardial calcinosis and mitral annular calcification) and the duration of hemodialysis (p = 0.015). While it was statistically insignificant, subjects showing MDP uptake were elder and had higher serum Ca or Ca x P product and lower intact parathyroid hormone levels. These results suggest that cardiac calcinosis in ESRD patients can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP.     

Changes in the prognosis for survival of patients with end-stage renal disease (ESRD) treated by hemodialysis

We started dialysis treatment in our institution in 1966, and have improved hemodialysis (HD) treatment through the induction of a biocompatible dialysis membrane, recombinant human erythropoietin, activated vitamin D and purification of the dialysate. We verified improvement of the prognosis for survival of patients with ESRD during this forty-year period, retrospectively. A total of 1,690 patients who began dialysis therapy in our hospital between January 1966 and December 2005 was studied (men: 1,047, women: 643, age: 58.6 +/- 17.4 years. They were divided into four groups (A: patients who started dialysis in the period from 1966 to 1975; n = 280, B: 1976-1985; n = 455, C: 1986-1995; n = 499, D: 1996-2005; n = 456). The mean follow-up period was 8.48 +/- 8.53 years. Of the patients 1,588 were treated with HD, 78 with peritoneal dialysis (PD), and 24 with PD or HD. Age at the initiation of dialysis increased gradually (A: 40.1 +/- 14.2 y-o, B: 53.2 +/- 15.8 y-o, C: 60.0 +/- 16.0 y-o, D: 66.4 +/- 13.8 y-o), and diabetics increased (A: 6.4%, B: 19.5%, C: 25.6%, D: 33.4%). A total of 1,180 patients died; 48.5% of these patients died of cardiovascular disease, 21.3% of infectious disease, and 6.4% of malignancy. Only 13 patients had kidney-transplants. With the Cox proportional hazard model for HD cases, age at the initiation of dialysis, gender, cause of renal disease, and the periods were significant predictors of mortality. The relative risk of mortality compared with that in A was reduced progressively: 0.796 in period B (95% confidence interval [CI]: 0.659-0.961, p = 0.0178), 0.505 in period C (95% CI: 0.409-0.623, p < 0.0001), and 0.286 in period D (95% CI: 0.223-0.366, p < 0.0001). CONCLUSIONS: Although the number of high-aged patients or diabetics with ESRD increased in these 40 years, the survival of the patients with ESRD improved.     

Haemodialysis increases QT(c) interval but not QT(c) dispersion in ESRD patients without manifest cardiac disease.

BACKGROUND: HD has been reported to determine an increase in QTc interval and QTc dispersion (QT(max)-QT(min))-risk factors that predispose to severe ventricular arrhythmias and sudden death. However, most studies have included end-stage renal disease (ESRD) patients with significant heart pathology. We therefore aimed to study the impact of a single HD session in subjects without manifest cardiac disease. METHODS: Sixty-eight stable, non-diabetic HD patients (47.1% males, age 40.2+/-12.7 years, HD duration 57+/-36 months and 37% hypertensive), with normal maximal ECG stress test and sub-endocardiac viability index and without ECG left ventricular hypertrophy were included. QT interval was calculated 10 min pre- and post-HD, as an average of three consecutive complexes, and corrected for heart rate using Bazett's formula (QTc=QT/(R-R)(1/2)). Na(+), K(+), Ca(2+), PO(4), pH and BP levels were also determined pre- and post-HD. RESULTS: The QTc interval increased significantly post-HD to 434+/-29 from 421+/-26 ms pre-HD (P=0.005); an abnormally prolonged QTc (>440 ms) was recorded in 34% cases pre-HD and in 46% post-HD, i.e. 1.5-2.3 times higher than in the high risk EURODIAB IDDM population. However, this effect was not homogeneous. Only 47 subjects had an increase in QTc duration after a dialysis session, while in 21 a decrease in QTc duration was recorded. The increase in QTc post-HD correlated with Ca(2+) homeostasis. Patients with greater increases in QTc after dialysis had higher baseline plasma calcium levels (r=0.47, P<0.001); also, a larger decrease in Ca(2+) post-HD correlated with higher increases in QTc interval (r=0.33, P<0.05). In contrast with QTc behaviour and with data from the literature, in this young HD population without manifest cardiac disease and with a low prevalence of HTA, post-HD QTc dispersion was similar to pre-HD values, increasing in only 39 patients. Furthermore, changes in QTc dispersion were not related to changes in electrolytes and BP following dialysis. However, changes in QTc dispersion and in QTc interval were directly correlated (r=0.37, P=0.42). There were no relationships between pre-HD measured echocardiographic variables, including: LV ejection fraction, internal diameters, wall thickness, mass and mass index and baseline or changes in QTc or QTc-d. CONCLUSIONS: Haemodialysis increases the QTc interval in ESRD patients, mainly related to rapid changes in electrolyte plasma concentrations. However, the impact on QTc dispersion is less important in the absence of significant coexisting cardiac disease.     

Low-output left ventricular failure in end-stage renal disease

To determine the factors associated with low-output left ventricular failure (LVF) in endstage renal disease (ESRD), we performed echocardiography and gated cardiac scan on 217 nondiabetic dialysis and transplant patients. The prevalence of low-output LVF (ejection fraction less than 55% and left ventricular end diastolic diameter greater than or equal to 5.5 cm) in dialysis patients was 18% and in transplant patients 2%. The 26 patients with LVF were compared to 52 controls without LVF, matched by age, sex and year of starting treatment for ESRD, but not for current ESRD therapy. Mean age was 55 +/- (SEM) 14 years; 73% of the patients in both groups were males. Duration of treatment for ESRD was 5.6 +/- 4.3 years in patients, compared to 5.1 +/- 4.1 years in controls. Significant differences between LVF patients and controls included current treatment (73% of cases were on hemodialysis and 8% were transplanted, compared to 48 and 42%; chi 2 = 9.9, p less than 0.01), high serum creatinine, smoking and high serum alkaline phosphatase. There were no differences for current blood pressure, proportion on treatment for hypertension, left ventricular wall thickness, symptomatic ischemic heart disease, proportion with functioning vascular access, degree of weight gain between dialyses, hemoglobin level or high transfusion requirement. Multiple logistic regression demonstrated the most significant and independent variables associated with LVF were high alkaline phosphatase (suggestive of hyperparathyroidism), smoking and high serum creatinine levels (reflecting degree of uremia). Dialysis patients with LVF (n = 23) were compared to dialysis patients who had normal echocardiograms (n = 29).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in fat mass after initiation of maintenance dialysis is influenced by the uncoupling protein 2 exon 8 insertion/deletion polymorphism.

BACKGROUND: A high body mass index (BMI) has been reported to confer a survival advantage in end-stage renal disease (ESRD) patients. On the other hand, body fat accumulation, especially visceral adipose tissue, is an important risk factor for cardiovascular disease, as well as a clinically important source of adipokines. Uncoupling protein 2 (UCP2) uncouples respiration from ATP synthesis, thus regulating energy expenditure and fat oxidation. In this longitudinal cohort study, we investigated the impact of the UCP2 insertion/deletion (ins/del) polymorphism on body composition changes in ESRD patients starting dialysis. METHODS: A total of 222 incident Caucasian ESRD patients (mean age 53 +/- 12 years; 60% males) were investigated close to the start of dialysis with peritoneal dialysis (PD; n = 126) or haemodialysis (HD; n = 96), and again after about 1 year (n = 159). Genotyping of the UCP2 ins/del polymorphism was performed in the patients and in 207 healthy controls. Dual-energy X-ray absorptiometry was conducted at baseline and after 1 year to monitor body composition. RESULTS: While HD patients and PD patients with the ins/del genotype did not display any changes in body composition, the 48 PD patients with the del/del genotype that completed follow-up had a significant increase; DeltaBMI (0.7 +/- 1.8 kg/m(2)), Deltabody fat mass (3.5 +/- 3.8 kg) and Deltatruncal fat mass (1.7 +/- 1.2 kg). In a multiple linear regression analysis, the del/del genotype was an independent predictor of the increase in truncal fat mass in PD patients (F-ratio = 7.99, P < 0.05) together with age and diabetes mellitus. CONCLUSIONS: PD patients, but not HD patients, with the UCP2 del/del genotype showed a significant increase in total and truncal fat mass during the first year of dialysis therapy, suggesting a possible role for UCP2 in dissipating the excess energy of a high-glucose environment.     

Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure.

BACKGROUND: Congestive heart failure (CHF) is an independent risk factor for mortality in the end-stage renal disease (ESRD) population. Nocturnal haemodialysis (NHD), a novel mode of renal replacement therapy, may be more effective than conventional haemodialysis in reducing intravascular volume or in removing uraemic toxins with vasoconstrictor or myocardial depressant actions, and may, therefore, improve the left ventricular (LV) systolic function of patients with coexisting cardiac and renal failure. METHODS: To test this hypothesis, we determined, in six patients (mean age+/-SD: 49.5+/-9 years), blood pressure (BP), ejection fraction (EF: radionucleotide angiography), left ventricular mass index (LVMI: echocardiography), LV fractional shortening (FS), and extracellular fluid volume (ECFV: bioelectrical impedance): before and after a mean of 3.2+/-2.1 years following conversion from conventional dialysis (3 days/week x 4 h) to NHD (6 nights/week x 8-10 h). RESULTS: There were significant reductions in systolic and mean arterial BP (138+/-10 to 120+/-9 mmHg, P=0.04; 99+/-6 to 86+/-7 mmHg, P=0.01). There was a significant increase in EF (28+/-12 to 41+/-18%, P=0.01) and a trend to greater LV FS (20+/-10 to 38+/-17%, P=0.06). Post-dialysis ECFV was not affected by dialysis mode (18.5+/-5.1 vs 18.2+/-3.5 l, P=0.76). The number of prescribed cardiovascular medications was reduced (2.2-0.7, P=0.02). CONCLUSIONS: In ESRD patients with systolic dysfunction, NHD leads to a sustained increase of EF and a reduction in the requirement for vasoactive medications in the absence of any reduction in post-dialysis ECFV.     

Cardiovascular care in end-stage renal disease

Cardiovascular disease (CVD) accounts for the majority of morbidity and mortality in patients with end-stage renal disease (ESRD). Chronic kidney disease, and ESRD as its most severe form, are now acknowledged to be independent risk factors for CVD. The spectrum of CVD includes accelerated atherosclerosis, myocardial disease and heart failure, cardiac arrhythmias, and valvular heart disease. In addition, CKD and ESRD are independent and powerful factors that complicate cardiovascular procedures and have been directly linked to increased mortality. This issue of Advances in Chronic Kidney Disease will explore the spectrum of risk and the opportunities to improve care in ESRD in outpatient management, during dialysis, after kidney transplantation, and in coronary revascularization.     

Improved left ventricular mass index in children after renal transplantation

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, and it is prevalent in children with end-stage renal disease (ESRD) and after renal transplantation (RTx) on cross-sectional studies. Our aim was to compare prospectively left ventricular mass index (LVMI) in children with ESRD, before and after RTx. Thirteen patients aged 1.5-15 years underwent echocardiogram prior to and at least 3 months after RTx, and again in the second year after transplantation. A control group consisted of children with ESRD who remained on dialysis. Systolic and diastolic blood pressure index decreased significantly over the study period only in the children who had undergone RTx. Mean LVMI in children with ESRD decreased from 45.4 +/- 12.6 g/m(2.7) to 34.9 +/- 10.4 g/m(2.7) after RTx (P = 0.001), but it remained unchanged in patients who remained on dialysis. The prevalence of LVH decreased from 54% to 8% (P = 0.03) after RTx. Systolic and diastolic blood pressure index were correlated with LVMI. Mean body mass index increased during the study period from 17.3 +/- 2.5 to 20 +/- 4.6 (P = 0.05); however, no correlation was found with LVMI. LVH in children with ESRD is potentially reversible after RTx, especially with good control of hypertension.     

Cardiovascular disease in pediatric chronic dialysis patients

BACKGROUND: Little information is available regarding cardiac morbidity and mortality in children with end-stage renal disease. We sought to determine the incidence of cardiac morbidity and mortality in pediatric chronic dialysis patients. METHODS: Medicare incident pediatric (0 to 19 years) dialysis patients from 1991 to 1996 were identified from the United States Renal Data System. Study endpoints included development of arrhythmia, valvular heart disease, cardiomyopathy, or cardiac arrest, all causes of death, and cardiac-related death. Statistical analyses were performed using the Poisson regression model and chi-square test. RESULTS: A total of 1454 children were eligible for inclusion, 452 (31.1%) of whom developed a cardiac-related event. Arrhythmia was the most common event (19.6%) compared with valvular disease (11.7%), cardiomyopathy (9.6%), and cardiac arrest (3%). Arrhythmia and valvular heart disease incidence were increased in 15- to 19-year-olds (P < 0.0001 for both), females (P = 0.004, P = 0.03) and blacks (P < 0.0001, P = 0.002). Cardiomyopathy incidence was increased in blacks (P = 0.001) and tended to be increased in females (P = 0.053). The adjusted annual cardiomyopathy rate during the first 3 years increased between 1991 and 1996 (P = 0.003). Death occurred in 107 patients, and 41 (38%) were cardiac deaths. CONCLUSIONS: Cardiovascular disease is a significant cause of morbidity and mortality in pediatric chronic dialysis patients. Cardiomyopathy incidence is increasing. Black, female, and adolescent children have increased risk for cardiovascular disease.     

Predialysis management and predictors for early mortality in uremic patients who die within one year after initiation of dialysis therapy

Despite improvements in dialysis therapy, the mortality rate of patients with end stage renal disease (ESRD) has remained high. A relatively high proportion of uremic patients dies within one year after the initiation of dialysis treatment. The aim of this study was to evaluate predictors for this early mortality in patients with ESRD. A total of 66 uremic patients were included in the study. Patients were divided in those who survived < 1 year (n = 17) and those who survived > or = 1 year (n = 49). We compared the prevalence of diabetes and hypertension and of vascular diseases as well as the prevalence of heart insufficiency (EF < 30%) and left ventricular hypertrophy (LVH). Additionally, we estimated the laboratory parameters serum creatinine, creatinine clearance, BUN, cholesterol, triglycerides, fibrinogen, serum protein, serum albumin and hemoglobin, and evaluated the indications for the initiation of dialysis therapy in both patient groups. The patients with survival < 1 year were significantly older (64+/-12 vs. 54+/-14 years, p<0.01) and showed a lower BMI (22+/-3 vs. 25+/-3, p<0.01) than those who survived > 1 year. The prevalence of diabetes (70% vs. 31%, p<0.05), cardiac insufficiency (70% vs. 16%, p<0.025), cardiovascular disease (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%, p<0.05) was significantly higher in the patients with early mortality. The prevalence of hypertension was similar in both groups, however, the prevalence of LVH was significantly higher in the patients who survived < 1 year (88% vs. 37%, p<0.05). Laboratory parameters were not significantly different in the two groups of patients, with the exception of serum albumin, which was significantly lower in the patients with early mortality (3.5+/-0.6 vs. 3.9+/-0.4 g/l, p<0.02). Hyperhydration was the most common indication for the start of dialysis in patients with early mortality (59% vs. 13%, p<0.025). Cardiac insufficiency was the most common cause of death in these subjects (n = 10, 59%). Six individuals (12%) died within four weeks after initiating dialysis therapy. Thus, there are several predictors for early mortality in end-stage renal disease patients, including high age, low BMI, the presence of diabetes, coronary heart disease, heart insufficiency and LVH, as well as low serum albumin levels. A relatively high percentage of patients die shortly after the start of dialysis therapy. Heart insufficiency is the most common cause of early death in these patients.     

Aortic pulse wave velocity index and mortality in end-stage renal disease

BACKGROUND: Aortic pulse wave velocity (PWV) is a strong independent predictor of overall and cardiovascular mortality in patients with end-stage renal disease (ESRD). Nevertheless, because age, blood pressure, heart rate, and gender are strong determinants of both arterial stiffness and mortality, the individual relevance of PWV measurements remains controversial. METHODS: A cohort of 242 patients with ESRD undergoing hemodialysis was studied for a mean (+/- SD) duration of 78 +/- 46 months. At entry, together with standard clinical and biochemical analyses, PWV was measured using Doppler ultrasonography. On the basis of a nomogram established on 469 nonuremic subjects, a theoretical value of PWV was determined in ESRD patients according to their age, blood pressure, gender, and heart period. The PWV index (measured PWV - theoretical PWV) was then calculated for each individual ESRD patient. RESULTS: Based on Cox analysis, the PWV index, but neither pulse pressure nor cardiac mass, was a strong and independent predictor of both cardiovascular and overall mortality, together with age and time on dialysis before inclusion. Patients with positive (versus negative) PWV index had a twofold adjusted risk of mortality during the follow-up. Per each 1 meter/second PWV index increment, we observed a 34% (crude) and a 14% (adjusted) increase in both cardiovascular and overall mortality (P < 0.02 for all). CONCLUSION: In ESRD patients, the calculation of a PWV index provides information about cardiovascular and overall mortality risk with high predictive power, showing that PWV measurements provide discriminatory prognostic power over and above conventional cardiovascular risk factors.     

Vascular calcification in dialysis patients

The risk factors for vascular calcification (VC) in dialysis patients include duration of dialysis, diabetes mellitus, aging, hyperphosphatemia, hyperparathyroidism, and calcium or vitamin D supplementation. This study was performed to evaluate the prevalence of and risk factors for VC in our dialysis population. METHODS: One hundred twenty-nine chronic dialysis patients underwent plain x-rays of the hands for VC. Patients were grouped as either positive (PVC) or negative (NVC) for VC. Age, gender, duration of dialysis, presence of non-insulin-dependent diabetes mellitus (NIDDM), oral calcium, and 1alpha-hydroxyvitamin D3 supplement, serum levels of calcium (Ca), phosphorus (P), calcium phosphorus product (CaxP), alkaline phosphates (ALP) and intact parathyroid hormone (iPTH) were compared between the two groups. RESULTS: Thirty-four patients (26.35%) showed VC. There were no differences between PVC and NVC patients for duration of dialysis (38.4 +/- 27.7 for PVC and 34.6 +/- 31.2 months for NVC, P = .80), levels of serum Ca (P = .26), P (P = .19), CaxP (P = .33), ALP (P = .89), or iPTH (P = .24). Similarly, oral calcium and 1alpha-hydroxyvitamin D3 intake were not different between the two groups (P = .971 and P = .3710 respectively). Compared to NVC patients, PVC patients were older (56.3 +/- 10.4 versus 47.5 +/- 16.1 years, P = .008) and had a greater incidence of NIDDM (17/34 PVC and diabetic versus 20/95 NVC, P = .001). In conclusion, for patients with a medium length of dialysis, the duration of dialysis as well as the doses of calcium salts and of 1alpha-hydroxyvitamin D3 were not significantly associated with vascular calcifications, but it was not possible to exclude a role for these and other factors in patients with longer dialysis.     

Postischemic vasodilation, endothelial activation, and cardiovascular remodeling in end-stage renal disease

BACKGROUND: Cardiovascular complications are the major cause of death in end-stage renal disease (ESRD) patients. These complications are associated with concomitant cardiac and vascular remodeling, including left ventricular (LV) hypertrophy and hypertrophy of arterial walls. The endothelium influences the process of arterial remodeling. ESRD patients are characterized by the development of both cardiovascular remodeling and endothelial dysfunction. METHODS: Common carotid artery (CCA) intima-media thickness (IMT), CCA diameter, CCA distensibility, LV mass, and function were determined in 60 stable ESRD patients on hemodialysis and 34 age-, sex-, and blood pressure (BP)-matched controls, and their relationships with endothelial alterations were estimated by forearm postischemic vasodilation [flow debt repayment (FDR)] measured by venous plethysmography. We also evaluated the relationships between FDR and several cardiovascular risk factors or markers of inflammatory response or endothelial activation, for example, duration of dialysis, BP, smoking habits, cholesterol, parathormone (PTH), serum albumin, plasma fibrinogen, C-reactive protein (CRP), plasma homocysteine, plasminogen activator inhibitor (PAI-1), and von Willebrand factor (vWF). RESULTS: ESRD patients had increased LV mass, CCA diameter and CCA IMT, and had decreased CCA distensibility (P < 0.05). While the postischemic peak flow was comparable in controls and ESRD patients (29.2 +/- 9.1 vs. 27.9 +/- 0.2 mL/100 mL/min), FDR was lower in ESRD patients (116 +/- 31 vs. 88 +/- 32%, P < 0.001) because of the shorter duration of vasodilation (127 +/- 36 vs. 96 +/- 32 s, P < 0.001). The time to complete FDR was longer in ESRD patients (110 +/- 54 vs. 162 +/- 72 s, P < 0.001). ESRD patients had lower high-density lipoprotein cholesterol and serum albumin (P < 0.01) and higher triglycerides, fibrinogen, plasma homocysteine, vWF (P < 0.01), and PAI-1 (P < 0.05). For ESRD patients, significant negative age- and pressure-independent correlations were established between FDR and CCA diameter, duration of dialysis, and PAI-1. FDR was positively correlated with serum albumin. FDR and time to FDR were negatively correlated with CCA IMT and LV mass. CCA distensibility was positively associated with FDR (P < 0.001) and negatively with time to FDR (P < 0.001). The PAI-1 concentration was positively correlated with CCA IMT (P < 0.01) and negatively with CCA distensibility (P < 0.001). CONCLUSIONS: Our data provide the first evidence that cardiac and arterial remodeling in ESRD patients are inversely related to forearm reactive hyperemia. The diminished hyperemic response is due to the shorter duration of hyperemia and is associated with higher concentrations of serum markers of endothelial activation, suggesting that, in ESRD patients, endothelial dysfunction may be a factor influencing cardiovascular changes.     

Detection and quantification of cardiovascular calcifications with electron beam tomography to estimate risk in hemodialysis patients

Cardiovascular disease is the leading cause of death in dialysis patients, accounting for nearly half of all deaths among end-stage renal disease (ESRD) patients. Even young dialysis patients are at risk. Cardiovascular disease in chronic renal failure patients has been associated with elevated serum phosphorus levels and elevated calcium-phosphorus (Ca x P) product, and mismanagement of calcium and phosphorus metabolism has been implicated as a major factor in the development of soft tissue calcification and cardiovascular disease. ESRD patients frequently face hyperphosphatemia as well as excess calcium load, which elevate the Ca x P product, thereby contributing to the development of calcific complications. Electron beam computed tomography (EBCT) can be used to detect different calcification stages in a variety of tissues, and is a sensitive tool for detecting calcified coronary artery plaques as well as cardiac and valvular calcifications. Hemodialysis patients have high calcium scores on EBCT imaging, and these are associated with elevations in Ca x P product. In a recent study, patients with calcification were found to have had twice the daily calcium intake from calcium-based phosphate binders than patients without calcification. Strategies to reduce cardiac risk in hemodialysis patients include use of a dialysate low in calcium, use of vitamin D analogs that are less calcemic, and use of calcium-free phosphate binders. EBCT can be a useful adjunct to these therapies, since it permits sensitive and quantitative initial assessment, as well as ongoing monitoring of disease progression.     

Assessment of phosphorus and calcium metabolism and its clinical management in hemodialysis patients in the community of Valencia

AIM: The objective of the study was to determine the situation concerning mineral metabolism and bone disease in hemodialysis (HD) patients living in the community of Valencia (Spain), as well as the clinical practices for bone disease control in relation to the laboratory targets recommended in the National Kidney Foundation Dialysis Outcomes Quality Initiative (K/DOQI) guidelines. METHODS: In December 2003, a cross-sectional study was performed including 2392 patients (1485 males and 907 females) from 43 different centers in the council of Valencia (the entire HD population). Mean age was 65.8 +/- 14 yrs. Cut-off levels for the study of calcium, phosphorus, calcium-phosphorus product (Ca x P) and parathyroid hormone (PTH) were performed following the recommendations of the K/DOQI guidelines. RESULTS: The mean values for calcium were 9.57 +/- 0.7 mg/dL, phosphorus 4.97 +/- 1.5 mg/dL, intact PTH (iPTH) 297 +/- 353 pg/mL, Ca x P 47.5 +/- 15 mg2/dL2. Hypocalcemia (<8.4 mg/dL) was present in 5% of patients, whereas 17.8% of patients presented hypercalcemia (>10.2 mg/dL), 60.3% of whom received vitamin D. Hypophosphoremia (<3.5 mg/dL) was present in 16% of patients, and 29% of patients presented hyperphosphoremia (>5.5 mg/dL). Ca x P was <55 mg2/dL2 in 73% of patients. Thirty one percent of patients presented secondary hyperparathyroidism (HPTH >300 pg/mL), being severe in 12% (>600 pg/mL); 43% of patients presented iPTH <150 pg/mL. Only 7.3% of patients achieved the four recommendations provided in the K/DOQI guidelines. Vitamin D treatment was administered in 48% of patients. CONCLUSIONS: The population undergoing dialysis in the community of Valencia achieved targets based on the clinical recommendations of the K/DOQI guidelines as follows: 45% of patients achieved targets for calcium, 55% for phosphorus, 73% for Ca x P and 26% for iPTH levels. Surprisingly, only 7.3% of patients achieved all four targets.