Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial.

BACKGROUND: Whether the use of sevelamer rather than a calcium-containing phosphate binder improves cardiovascular (CV) survival in patients receiving dialysis remains to be elucidated. STUDY DESIGN: Open-label randomized controlled trial with parallel groups. SETTINGS & PARTICIPANTS: 466 incident hemodialysis patients recruited from 18 centers in Italy. INTERVENTION: Study participants were randomly assigned in a 1:1 fashion to receive either sevelamer or a calcium-containing phosphate binder (although not required by the protocol, all patients in this group received calcium carbonate) for 24 months. OUTCOMES: All individuals were followed up until completion of 36 months of follow-up or censoring. CV death due to cardiac arrhythmias was regarded as the primary end point. MEASUREMENTS: Blind event adjudication. RESULTS: At baseline, patients allocated to sevelamer had higher serum phosphorus (mean, 5.6 ± 1.7 [SD] vs 4.8 ± 1.4 mg/dL) and C-reactive protein levels (mean, 8.8 ± 13.4 vs 5.9 ± 6.8 mg/dL) and lower coronary artery calcification scores (median, 19 [IQR, 0-30] vs 30 [IQR, 7-180]). At study completion, serum phosphate levels were lower in the sevelamer arm (median dosages, 4,800 and 2,000 mg/d for sevelamer and calcium carbonate, respectively). After a mean follow-up of 28 ± 10 months, 128 deaths were recorded (29 and 88 due to cardiac arrhythmias and all-cause CV death). Sevelamer-treated patients experienced lower CV mortality due to cardiac arrhythmias compared with patients treated with calcium carbonate (HR, 0.06; 95% CI, 0.01-0.25; P < 0.001). Similar results were noted for all-cause CV mortality and all-cause mortality, but not for non-CV mortality. Adjustments for potential confounders did not affect results. LIMITATIONS: Open-label design, higher baseline coronary artery calcification burden in calcium carbonate-treated patients, different mineral metabolism control in sevelamer-treated patients, overall lower than expected mortality. CONCLUSIONS: These results show that sevelamer compared to a calcium-containing phosphate binder improves survival in a cohort of incident hemodialysis patients. However, the better outcomes in the sevelamer group may be due to better phosphate control rather than reduction in calcium load.

Coronary artery calcification progression is associated with arterial stiffness and cardiac repolarization deterioration in hemodialysis patients.

BACKGROUND/AIMS: Evidence suggests that vascular calcification (VC) portends poor cardiovascular (CV) prognosis in patients undergoing maintenance dialysis (CKD-5). Nonetheless, how VC might predispose to CV mortality still remains to be clarified. Herein, we report on the association between coronary artery calcification (CAC) progression and changes in cardiac repolarization as well as arterial stiffness. METHODS: 132 patients new to dialysis were identified. Demographic and clinical characteristics were collected at study entry and during the 12-month follow-up. CAC, 12-lead ECG and pulse wave velocity (PWV) were assessed at baseline and study completion. Uni- and multivariable analyses were applied to detect factors associated with worsening of cardiac repolarization (QTd) and arterial stiffness (PWV). RESULTS: Uni- and multivariable analyses revealed that CAC progression was associated with a significant increase in both QTd and PWV. Every 20-unit increase in the CAC score corresponded to a significant 23% (95% CI 1.12-1.27; p < 0.001) and 32% (95% CI 1.09-1.37; p < 0.01) increase in the risk of experiencing a 1-m/s increase in PWV and 1 ms in QTd, respectively. CONCLUSION: VC is a marker of vasculopathy and appears to be associated with cardiac repolarization and arterial stiffness abnormalities in CKD-5 patients.

Reproducibility of regional pulse-wave velocity in uremic subjects.

Despite the clinical importance of pulse-wave velocity (PWV), there are no standards for accurate carotid-radial pulse-wave measurement in uremic patients with respect to carotid-femoral measurement. We assessed the reproducibility of PWV values using the carotid-radial PWV measurement. We have measured the carotid-femoral PWV and carotid-radial PWV with an automated system (Pulse Pen, DiaTecne) using 2 different blind operators in 105 hemodialysis (HD) patients. The carotid-femoral waveforms were acquired by the first blind operator simultaneously with 2 pressure-sensitive transducers and the transit time of the pulse was calculated using the system software. Similarly, the second blind operator acquired the carotid-radial waveforms. The two operators performed 2 consecutive measurements from the same subject, in a random order. In fact, after the first operator had completed 2 consecutive measurements from 1 subject, all of the sensors were detached, and the second operator attached sensors again to the same subject. The measurements were performed during interval of a midweek dialysis-free day. To evaluate the reproducibility of the system, both within-observer and between-observer analyses were performed. We studied 105 dialysis patients (HD) and 20 controls. All HD patients had three dialysis sessions lasting at least 4 h/wk. A total of 28 patients (26.7%) had diabetic nephropathy. The mean age of HD was 64.6 ± 16.1 years, the body weight was 71.1 ± 15.1 kg, and the height was 164.6 ± 6.1 cm. All population studied is referral at a tertiary care from at least 6 months (mean 11.1 ± 2.1 months). A total of 45% of patients are smokers or ex-smokers. The PWV of carotid-femoral is 8.58 ± 3.99 and the PWV of carotid-radial is 8.70 ± 4.01 m/sec, respectively, by the first and the second operator; the difference of PWV (femoral-radial measure) is -0.037 ± 0.99 m/sec. The linear correlation of carotid-femoral vs. carotid-radial PWV measurements is the highest (R(2) =0.90). The results regarding reproducibility, including mean differences and standard deviations, standard errors, and correlation coefficients were analyzed for each regional PWV value for the between-observer and within-observer studies. All of the measurements showed significant correlation coefficients, ranging from 0.94 to 0.98. The reproducibility of regional PWV values for 2 consecutive measurements from the same subject was also analyzed using Bland-Altman plots, with the reproducibility expressed as the mean difference and 2 standard deviations between the measurements obtained by the 2 operators during carotid-femoral and carotid-radial measurements. Carotid-radial PWV measurement provides an accurate analysis with a high reproducibility with respect to carotid-femoral PWV measurement, and it can be used for arterial stiffness analysis in hemodialysis patients.

Lanthanum carbonate is not associated with QT interval modification in hemodialysis patients.

UNLABELLED: Lanthanum carbonate is an efficacious noncalcium, nonresin phosphate-binder that is being increasingly used in chronic kidney disease stage 5 (CKD-5) dialysis patients. Available evidence has indicated that QT interval changes correlate with mortality in healthy subjects and in dialysis patients. Experimental studies have suggested the possibility that lanthanum carbonate may produce prolongation of the QT interval. This is not accepted by other authors. There is no data confirming this in prospective clinical studies. The goal of this study was to verify the effect of lanthanum carbonate on the QT interval of the electrocardiogram (EKG) tracing. MATERIAL AND METHODS: We studied 25 hemodialyzed patients. After a six-month run-in period, with aluminum-hydroxide, lanthanum carbonate was administered at increasing doses: 500 mg twice a day for week 1; 750 mg, twice daily during week 2; 1000 mg twice daily during week 3; and 1000 mg three times daily during week 4. EKGs were recorded on patients prior to and 3 hours following each dialysis treatment. Assessments were made of differences in body weight; systolic blood pressure; diastolic blood pressure; length of PR and QRS complex; heart rate; QT; QT-c; QT-d; and axis of wave P, QRS complex and T using lanthanum carbonate at increasing doses. RESULTS: QT-c is before dialysis session during run-in 431 ± 20 msec with variation by -9 to + 1 msec (P = not significant [NS]) during lanthanum use; and 437 ± 25 msec after dialysis session with variation by -6 to -1 msec (P = NS) during lanthanum use. Any difference was observed during study among before and after dialysis session in QT-c (difference by 0.09 to 3.2%) (P = NS); and QT-d (difference by 8.6 to 9.1%) (P = NS). CONCLUSION: Our study shows that lanthanum carbonate administration, at increasing doses, did not modify the EKG parameters. This effect is observed both in predialysis and in postdialysis recordings. Further studies are necessary with more prolonged observations.

Influence of haemodialysis on variability of pulse wave velocity in chronic haemodialysis patients.

BACKGROUND: The major determinants of pulse wave velocity (PWV) in haemodialysis (HD) patients are not fully known. We studied chronic HD patients to assess the effect of cyclic variations in both hydration status and blood pressure on PWV. METHODS: Twenty patients were examined along three consecutive HD sessions and interdialysis periods during a week-long period. Twenty healthy subjects and 20 chronic kidney disease (CKD) patients (stage 5) were evaluated as controls. RESULTS: In contrast to controls, HD patients showed cyclic changes in PWV. Specifically, PWV values in HD patients were significantly higher prior to the first HD session of the week compared with values measured prior to the other two HD sessions during the week. In addition, PWV showed significant reductions during each dialysis session (15.6 +/- 5.2 to 9.3 +/- 2.3, 13.4 +/- 4.0 to 8.7 +/- 2.4, and 12.4 +/- 2.6 to 9.2 +/- 2.2 m/sec, before and after the first, second and third weekly dialysis sessions, respectively). Nevertheless, the weighted weekly values of PWV in HD patients (10.8 +/- 5.7 m/sec) were similar to those in CKD patients (9.9 +/- 4.2 m/sec). The HD ultrafiltration rate (UF) was significantly correlated with intradialysis PWV changes (r = 0.465; P < 0.001) and with after dialysis PWV values (r = -0.654; P < 0.0001). Blood pressure changes during dialysis were weakly correlated with post-dialysis PWV (r = -0.267; P < 0.05), but not with PWV changes during dialysis. CONCLUSIONS: In chronic HD patients, single PWV values varied widely during 1 week of HD sessions, whereas the weighted level showed only a slight increase. The major determinant of changes in PWV during HD appears to be the alterations in hydration status; the most representative time point for PWV measurements during HD corresponds to the interdialysis days.

Vascular calcification and QT interval in incident hemodialysis patients.

This study proposes [corrected] to evaluate the impact of different phosphate binders on the slowing of [corrected]cardiovascular calcification [corrected] and QT dispersion in incident haemodialysis patients with a follow-up of [corrected] 36 months. This is to be a [corrected] randomized, multicenter, perspective, [corrected] interventional study. Inclusion criteria are age over 18 years and being an [corrected] incident patient [corrected] on hemodialysis. Exclusion criteria are congenital prolongation of QT segment syndrome, QT-c >440 ms, bradycardia <50 beats per minute, symptomatic [corrected] arrhythmia or any other significant heart problems; electrolyte imbalances [corrected] (especially hypokalemia, hypomagnesemia or [corrected] hypocalcemia); abnormal liver function tests and [corrected] hypothyroidism. An informed consent will be taken at study entry. The patients will be randomized to 2 cohorts: [corrected] 180 patients in the sevelamer [corrected] group and 180 patients in calcium-binder phosphate group. Related vascular calcification mortality is the principal end point [corrected] and will be evaluated at 36 months.

Survey of hidden costs of dialysis in Italian for-profit and not-for-profit centers.

BACKGROUND: Chronic dialysis exposes patients to several procedures that may influence lifestyle and quality of life. These hidden costs, however, have never been evaluated. AIM AND METHODS: To compare the costs related to diagnostic and therapeutic procedures between not-for-profit (nFP) and for-profit (FP) dialysis care systems, we mailed to Italian nephrology units a questionnaire on modalities of medical prescriptions and reservations, waiting time for tests and modalities of drugs distribution. RESULTS: 247 centers (42%) replied to the questionnaire: 177 nFP (72%) and 70 FP (28%). The response rate was 54% of nFP and 26% of FP centers. All centers provided hemodialysis (in satellite units, 42% nFP and 14% FP, p<0.001; at home, 23% nFP and 1% FP, p<0.001). Peritoneal dialysis was offered by 60% nFP and 6% FP (p<0.001). Centers provided dialysis care for 15,294 patients, 85% in nFP and 15% in FP. At least 1 general practitioner prescription for dialysis, diagnostic tests, specialist consultations and drugs, was requested to patients in 50% of nFP and 95% of FP centers (p<0.001). Reservations for tests and specialist visits were made by patients in 6% of nFP and 20% of FP centers (p<0.001). In nFP and FP centers, waiting time for tests was 2 vs. 4 days for lung x-ray (p<0.01), 7 vs. 11 days for gastroscopy (p<0.05) and 14 vs. 13 days for echocardiography (NS). Erythropoietin, phosphate binders and nutritional supplements, were supplied by patients in 7%, 46% and 37% of nFP centers, and 86%, 86% and 90% of FP centers (p<0.001). CONCLUSIONS: The dialysis care system charges patients a high hidden cost, represented by procedures related to dialysis. Higher costs and reduced choice of treatment modalities may characterize the for-profit dialysis system.

Burn-out in the dialysis unit.

The management of human resources is definitely one of the most important chapters in managerial activities. So, the involved participation of personnel is one of fundamental importance for all systems of quality management. The aim of this study is to analyse satisfaction of personnel in dialysis units. We administered a questionnaire subdivided into 6 basic sections with 34 items regarding the work environment, the material, the environmental climate, the objectives, the quality, and justifications and suggestions. We received 298 replies to the questionnaire, of which 72 from doctors (D) (24.2%) and 226 from nurses (N) (75.8%). From a possible maximum score of 170, the scores reached were 115 points for the D and 113 for the N. It is obvious that N considered the environmental climate, the objectives and the quality of the services to be inferior compared to D. Thirty-nine percent of D and 27% of N were very critical of the items analyzed. A second step was dedicated to the administration of the questionnaire to the dialysis patients to verify if there was agreement. One hundred and twenty-five patients (5.7%) (randomized in a single dialysis unit for age and sex), of a total of 2170 patients responded. Their answers were then compared with those of the personnel. The data of our study showed that most of the personnel did not receive counseling about uncertainties, expectations did not correspond to reality and there was distrust and scarcity of involvement. These elements appeared to cause irritation and dissatisfaction and if not resolved are responsible, together with technical and environmental factors, for the serious burn-out syndrome in the personnel of dialysis units.

Long-term L-carnitine administration reduces erythropoietin resistance in chronic hemodialysis patients with thalassemia minor.

BACKGROUND AND AIM: Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in ß-thalassemic on chronic hemodialysis. METHODS: We studied twelve subjects (M = 8; F = 4) affected by ß-thalassemia minor (ß-thal; HbA2 level = 6.6 ± 0.6%) and forty non-thalassemic subjects (M = 24; F = 16) as controls (C), on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11-12g/dl) prior to the study and underwent to i.v. L-carnitine administration for a one year period-time. RESULTS: Groups were comparable for age, gender, serum levels of hemoglobin (Hb), iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed significant Hb increase and erythropoietin (EPO) decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in ß-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in ß-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl; NS); along carnitine administration period, however, MCV during dialysis decreased also in ß-thal, starting since the 9th month of treatment. CONCLUSION: This study provides evidence of the lowering of EPO resistance in ß-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by ß-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

Cardiac vascular calcification and QT interval in ESRD patients: is there a link?

We will present our experience and our preliminary data about the correlation between cardiac calcification and QT interval (and QT dispersion) in uraemia. We studied 32 haemodialysis (HD) patients (age 69 +/- 16 years, time on dialysis 32 +/- 27 months) and 12 chronic kidney disease stage 4 (CKD-4) patients (age 66 +/- 17 years, uraemia duration 38 +/- 16 months). The patients were characterized by a good mineral control, as shown by serum phosphate levels (3.6 +/- 1.3 mg/dl in CKD-4 and 4.3 +/- 1.6 mg/dl in HD patients) and Ca x P product (46 +/- 17 and 49 +/- 16 mg(2)/dl(2), respectively). The parathyroid hormone levels were higher in HD than CKD-4 patients (p < 0.0001). A TC score >400 was found to be highly prevalent in both groups. Significantly more HD patients (62.5%) showed cardiac calcification than CKD-4 patients (33%; p = 0.01). The patients were matched for TC scores higher or lower than 400. The two groups differed by gender (p < 0.05), age (p = 0.026), frequency of diabetes mellitus (p < 0.01), uraemia follow-up period (p < 0.001), low-density lipoprotein cholesterol level (p = 0.009), Ca x P product (p = 0.002), parathyroid hormone level (p < 0.0001), and corrected QT dispersion (p < 0.0001). The QT interval was higher in HD and CKD-4 patients with higher TC scores (approximately 11%), but QT interval dispersion was significantly higher in patients with TC scores >400. QT dispersion showed a linear correlation with TC scores in both groups (r = 0.899 and p < 0.0001 and r = 0.901 and p < 0.0001). Male gender, age, time (months) of uraemia, low-density lipoprotein cholesterol, albumin, calcium x phosphorus product, parathyroid hormone, and TC score are important determinants of QT dispersion. Our data show that it is possible to link dysrhythmias and cardiac calcification in uraemic patients.

Unusual complication of central venous catheter in hemodialysis.

A case of a partial rupture of a cuffed central venous catheter (CVC) implanted in the femoral vein with the purpose of being used for chronic hemodialysis is described in a 74-year-old female patient. Of relevance is that the CVC described was from the same manufacturer as the previous one that had lasted 12 years.