Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.

Sudden death and associated factors in a historical cohort of chronic haemodialysis patients.

BACKGROUND: In haemodialysis patients, deaths due to cardiovascular causes constitute a large proportion of total mortality and sudden cardiac deaths account for approximately 22% of all deaths. The aim of this study was to evaluate the incidence of sudden cardiac death and associated risk factors in a cohort of haemodialysis patients. METHODS AND RESULTS: The 3-year cumulative incidence of death in a cohort of 476 patients on chronic haemodialysis treatment was 34.3% (SE 2.3). Sudden death had a 6.9% (SE 1.2) cumulative incidence, with 32 events representing 19.2% of all deaths, while cardiovascular not sudden death and noncardiovascular death accounted for a 3-year cumulative incidence of 7.3% (SE 1.2) and 20.1% (SE 1.9), respectively. According to Cox multivariate analysis, significant risk factors for sudden death were the presence of atrial fibrillation, diabetes mellitus, predialytic hyperkalaemia, haemodialysis mode and C-reactive protein level, which were associated with a 2.9 (CI(95%) 1.3-6.4), 3.0 (CI(95%) 1.3-7.2), 2.7 (CI(95%) 1.3-5.8), 4.5 (CI(95%) 1.3-15.5) and 3.3 (CI(95%) 1.2-8.8)-fold increase in the risk of sudden death, respectively. Sudden death was significantly more frequent during the first 24 h of the first short interdialytic interval and during the last 24 h of the long interval, i.e. immediately before and immediately after the first weekly haemodialysis session (P = 0.02). CONCLUSIONS: Our data show that the incidence of sudden death in haemodialysis patients is high and that atrial fibrillation, diabetes, hyperkalaemia, haemodialysis mode and C-reactive protein play an important role in developing fatal arrhythmia. Further studies will be necessary to define which interventions could be helpful in reducing this cause of mortality.

Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.

BACKGROUND: Atrial fibrillation is associated with increased mortality and hospitalization in the general population. Data about mortality, morbidity, and hospitalization in hemodialysis patients with atrial fibrillation are limited. SETTING & PARTICIPANTS: All patients (n = 476) in 5 dialysis centers in Lombardia, Italy, as of June 2003 were enrolled and followed up until June 2006 (median age, 69 years; median hemodialysis duration, 45.2 months; and median follow-up, 36 months). 127 patients had atrial fibrillation at enrollment. PREDICTORS & OUTCOME: A Cox model was used to relate: (1) atrial fibrillation, age, hemodialysis therapy duration, and comorbid conditions to all-cause and cardiovascular mortality; (2) angiotensin-converting enzyme (ACE)-inhibitor treatment and comorbid conditions to new onset of atrial fibrillation; and (3) atrial fibrillation and comorbid conditions on hospitalization. RESULTS: There were 167 deaths (39.5% from cardiovascular disease). In multivariable models, atrial fibrillation was independently associated with increased mortality (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.18 to 2.31). This was more notable for cardiovascular (HR, 2.15; 95% CI, 1.27 to 3.64) than noncardiovascular mortality (HR, 1.39; 95% CI, 0.89 to 2.15). New-onset atrial fibrillation occurred in 35 of 349 individuals (4.1 events/100 person-years); the risk of incident atrial fibrillation was lower in those using ACE-inhibitor therapy (HR, 0.29; 95% CI, 0.10 to 0.82) and higher in those with left ventricular hypertrophy (HR, 2.55; 95% CI, 1.04 to 6.26). There were 539 hospitalizations during 3 years, with 114 hospitalizations in 162 patients with atrial fibrillation and 155 hospitalizations in 314 patients without atrial fibrillation (HR, 1.54; 95% CI, 1.18 to 2.01). Rates of stroke did not significantly differ by atrial fibrillation status (P = 0.4). LIMITATIONS: Because of the observational nature of this study, results for treatment need confirmation in future trials. CONCLUSIONS: Atrial fibrillation is associated with greater total and cardiovascular mortality. Patients with atrial fibrillation were hospitalized more frequently than patients without atrial fibrillation. ACE inhibitors may decrease the risk of new-onset atrial fibrillation.

Prevalence of atrial fibrillation and associated factors in a population of long-term hemodialysis patients.

BACKGROUND: Hemodialysis (HD) is associated with cardiovascular structural modifications; moreover, during HD, rapid electrolytic changes occur. Both factors may favor the onset of atrial fibrillation. METHODS: To define the prevalence of atrial fibrillation and identify associated factors, 488 patients on long-term HD therapy (age, 66.6 +/- 13.4 years; men, 58.0%; duration of HD, 76.5 +/- 84.3 months) were studied. RESULTS: Atrial fibrillation was reported in 27.0% of patients; paroxysmal in 3.5%, persistent in 9.6%, and permanent in 13.9%. Clinical and echocardiographic variables were considered: patients with atrial fibrillation were older (71.8 +/- 9.3 versus 64.7 +/- 14.2 years; P < 0.01), and its prevalence increased with age. Patients with arrhythmia had a longer duration of dialysis therapy (93.2 +/- 100.5 versus 70.2 +/- 76.7 months; P = 0.02). Atrial fibrillation was associated significantly with ischemic heart disease (P < 0.01), dilated cardiomyopathy (P < 0.01), acute pulmonary edema (P < 0.05), valvular disease (P < 0.05), cerebrovascular accidents (P < 0.05), and predialytic hyperkalemia (P < 0.05). Patients with atrial fibrillation more frequently showed left atrial dilatation (59.8% versus 34.5%; P < 0.0001), and in these subjects, left ventricular ejection fraction was significantly lower (53.9% versus 57.4%; P = 0.029). No association was found between arrhythmia and hypertension or diabetes. Multivariate analysis confirmed that patient age (P < 0.001), duration of HD therapy (P = 0.001), and left atrial dilatation (P < 0.001) were associated with atrial fibrillation. CONCLUSION: Atrial fibrillation is much more frequent in HD patients than in the general population; age, duration of HD history, presence of some heart diseases, and left atrial dilatation are associated with the arrhythmia.