The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients. METHODS: De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH). RESULTS: 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day). CONCLUSION: In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

BACKGROUND: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. METHODS: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. RESULTS: In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P < 0.01. A multiple linear model confirmed that Mixed HDF vs Post-HDF reduced significantly ESA requirement and ESA resistance (P < 0.0001), by a mean of 29% (CI 23-35%) in the last three months of the observation periods. CONCLUSIONS: Mixed HDF decreased darbepoetin-alfa requirement in dialysis patients. This might help preventing the untoward side effects of high ESA doses, besides having a remarkable economic impact. Additional evidence is needed to confirm this potential benefit of Mixed-HDF.

A comparative study of the risk profile of hemodialysis patients in a for profit network and in two regional registries of the Italian Society of Nephrology.

In 2013, the Italian Society of Nephrology joined forces with Nephrocare-Italy to create a clinical research cohort of patients on file in the data-rich clinical management system (EUCLID) of this organization for the performance of observational studies in the hemodialysis (HD) population. To see whether patients in EUCLID are representative of the HD population in Italy, we set out to compare the whole EUCLID population with patients included in the regional HD registries in Emilia-Romagna (Northern Italy) and in Calabria (Southern Italy), the sole regions in Italy which have systematically collected an enlarged clinical data set allowing comparison with the data-rich EUCLID system. An analysis of prevalent and incident patients in 2010 and 2011 showed that EUCLID patients had a lower prevalence of coronary heart disease, peripheral vascular disease, heart failure, valvular heart disease, liver disease, peptic ulcer and other comorbidities and risk factors and a higher fractional urea clearance (Kt/V) than those in the Emilia Romagna and Calabria registries. Accordingly, survival analysis showed a lower mortality risk in the EUCLID 2010 and 2011 cohorts than in the combined two regional registries in the corresponding years: for 2010, hazard ratio (HR) EUCLID vs. Regional registries: 0.80 [95% confidence interval: 0.71-0.90]; for 2011, HR: 0.76 [0.65-0.90]. However, this difference was nullified by statistical adjustment for the difference in comorbidities and risk factors, indicating that the longer survival in the EUCLID database was attributable to the lower risk profile of patients included in that database. This preliminary analysis sets the stage for future observational studies and indicates that appropriate adjustment for difference in comorbidities and risk factors is needed to generalize to the Italian HD population analyses based on the data-rich EUCLID database.

Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients.

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.

Longitudinal Changes in Body Composition in Patients After Initiation of Hemodialysis Therapy: Results From an International Cohort.

OBJECTIVE: In patients with advanced kidney disease, metabolic and nutritional derangements induced by uremia interact and reinforce each other in a deleterious vicious circle. Literature addressing the effect of dialysis initiation on changes in body composition (BC) is limited and contradictory. The aim of this study was to evaluate changes in BC in a large international cohort of incident hemodialysis patients. METHODS: A total of 8,227 incident adult end-stage renal disease patients with BC evaluation within the initial first 6 months of baseline, defined as 6 months after renal replacement therapy initiation, were considered. BC, including fat tissue index (FTI) and lean tissue index (LTI), were evaluated by Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany). Exclusion criteria at baseline were lack of a BCM measurement before or after baseline, body mass index (BMI) < 18.5 kg/m(2), presence of metastatic solid tumors, treatment with a catheter, and prescription of less or more than 3 treatments per week. Maximum follow-up was 2 years. Descriptive analysis was performed comparing current values with the baseline in each interval (delta analysis). Linear mixed models considering the correlation structure of the repeated measurements were used to evaluate factors associated with different trends in FTI and LTI. RESULTS: BMI increased about 0.6 kg/m(2) over 24 months from baseline. This was associated with increase in FTI of about 0.95 kg/m(2) and a decrease in LTI of about 0.4 kg/m(2). Female gender, diabetic status, and low baseline FTI were associated with a significant greater increase of FTI. Age > 67 years, diabetes, male gender, high baseline LTI, and low baseline FTI were associated with a significant greater decrease of LTI. CONCLUSIONS: With the transition to hemodialysis, end-stage renal disease patients presented with distinctive changes in BC. These were mainly associated with gender, older age, presence of diabetes, low baseline FTI, and high baseline LTI. BMI increases did not fully represent the changes in BC.

Modifiable factors associated with achievement of high-volume post-dilution hemodiafiltration: results from an international study.

BACKGROUND: The aim was to investigate factors associated with the successful achievement of ≥21 l/session of substitution fluid volume in patients on post-dilution hemodiafiltration. METHODS: 3315 patients treated in 6 European countries with the Fresenius 5008 CorDiax machine including the AutoSub Plus feature were considered. Variables that showed a relationship with convection volume were entered in a multivariable logistic regression model. RESULTS: Mean blood flow was 379 ± 68 ml/min. Median substitution volume was 24.7 L (IQR 22.0-27.4 L). Mean filtration fraction was 28.3 ± 4.1%. 81.5% of sessions qualified as high-volume HDF (substitution volumes ≥21 L). Higher age, dialyzer surface area, blood flow and treatment time were positively associated with the achievement of ≥21 L substitution volume; higher body mass index, male gender, higher hematocrit, graft or catheter vs. fistula, and start of week vs. mid-week were negatively associated. CONCLUSIONS: Dialysis center policy in terms of blood flow, treatment time, filter size, and perhaps even hemoglobin targets plays a key role in achieving high-volume HDF. All of these are modifiable factors that can help in prescribing an optimal combination of dialyzer size, achievable blood flows, and treatment times.

Physical methods for evaluating the nutrition status of hemodialysis patients.

This article aims to provide an overview of the different nutritional markers and the available methodologies for the physical assessment of nutrition status in hemodialysis patients, with special emphasis on early detection of protein energy wasting (PEW). Nutrition status assessment is made on the basis of anamnesis, physical examination, evaluation of nutrient intake, and on a selection of various screening/diagnostic methodologies. These methodologies can be subjective, e.g. the Subjective Global Assessment score (SGA), or objective in nature (e.g. bioimpedance analysis). In addition, certain biochemical tests may be employed (e.g. albumin, pre-albumin). The various subjective-based and objective methodologies provide different insights for the assessment of PEW, particularly regarding their propensity to differentiate between the important body composition compartments-fluid overload, fat mass and muscle mass. This review of currently available methods showed that no single approach and no single marker is able to detect alterations in nutrition status in a timely fashion and to follow such changes over time. The most clinically relevant approach presently appears to be the combination of the SGA method with the bioimpedance spectroscopy technique with physiological model and, additionally, laboratory tests for the detection of micro-nutrient deficiency.

What causes an improved safety climate among the staff of a dialysis unit? Report of an evaluation in a large network.

BACKGROUND: Clinical staff's safety perception is considered an important indicator of the implementation level of safety climate and safety culture. For this purpose, the Safety Climate Survey Questionnaire was submitted to the dialysis clinics staff of the Fresenius Medical Care (FME) network in Italy. Moreover, to explore how standard procedures implementation influences staff opinion of safety levels, the Universal Hygiene Precautions Questionnaire was also submitted. METHODS: Safety Climate Survey and Universal Hygiene Precautions questionnaires were based on 19 and 14 statements, respectively. Staff members (n=346) of 33 dialysis units were involved: 21.4% physicians, 58.1% registered nurses and 20.5% health care assistants (HCAs). RESULTS: Safety Climate mean total score was 81.9%. Medical directors (91.5%) and quality-responsible head nurses (QHRNs) (87.4%) showed higher scores in comparison with staff physicians (82.4%), nurses responsible for hygiene (81.1%) and HCAs (78.8%). Staff nurses (78.9%) showed a significant difference (p<0.05) compared with medical directors. Universal Hygiene Precautions mean total score was 90.8%, not significantly different among medical directors (92%), staff physicians (91.4%), QHRNs (93.2%), nurses responsible for hygiene (91.7%) and staff nurses (91.4%). Only HCAs reported a significantly (p<0.05) lower score (83.6%) compared with medical directors. As the respondents were asked to complete both questionnaires anonymously, a direct correlation between the 2 questionnaires was not possible. CONCLUSION: A relatively high value for Safety Climate was evaluated within the FME network of Italian dialysis clinics. Management showed higher Safety Climate scores than frontline staff. Fostering communication and implementation of training programs are considered valid tools to improve safety.

[The value of early referral in the management of chronic kidney disease: NephroCare's eight years of interaction with general practitioners]. / L'early referral nella gestione della malattia renale cronica: l'esperienza della NephroCare di 8 anni di interazione con i medici di medicina generale.

It has been demonstrated that early diagnosis of chronic kidney disease (CKD) is important in containing the morbidity and mortality of this disease. It postpones the initiation of hemodialysis treatment and reduces the risk of complications. General practitioners (GPs) have a relevant part in this process because they are the first point of contact for persons in risk categories (e.g., diabetic and hypertensive patients). In 2002 NephroCare started a collaboration with GPs in the Italian region of Campania. This program, called Nephro Day, is aimed at screening patients with hypertension and diabetes, and identifying patients with CKD to reduce the late referral phenomenon. Meetings between GPs and Nephrocare nephrologists were held in which the etiology, pathology and risk factors associated with CKD as well as the screening options were discussed. Strong emphasis was placed on the importance of assigning CKD patients with hypertension and diabetes to 1 of the 5 stages of the DOQI guidelines. A clear positive correlation was observed between the age of diabetic and hypertensive patients and the risk of CKD. In the current situation of limited budgets and a limited number of nephrologists, the collaboration between GPs and specialists offers an unique opportunity to handle the problem of late referral, allowing timelier and more adequate treatment of patients with CKD and thus leading to substantial cost savings.

Effects of telmisartan added to Angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial.

OBJECTIVES: the aim of this study was to determine whether telmisartan decreases all-cause and cardiovascular mortality and morbidity in hemodialysis patients with chronic heart failure (CHF) and impaired left ventricular ejection fraction (LVEF) when added to standard therapies with angiotensin-converting enzyme inhibitors. BACKGROUND: in hemodialysis patients, CHF is responsible for a high mortality rate, but presently very few data are available with regard to this population. METHODS: A 3-year randomized, double-blind, placebo-controlled, multicenter trial was performed involving 30 Italian clinics. Hemodialysis patients with CHF (New York Heart Association functional class II to III; LVEF ≤ 40%) were randomized to telmisartan or placebo in addition to angiotensin-converting enzyme inhibitor therapy. A total of 332 patients were enrolled (165 telmisartan, 167 placebo). Drug dosage was titrated to a target dose of telmisartan of 80 mg or placebo. Mean follow-up period was 35.5 ± 8.5 months (median: 36 months; range: 2 to 40 months). Primary outcomes were: 1) all-cause mortality; 2) cardiovascular mortality; and 3) CHF hospital stay. RESULTS: at 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001). Adverse effects, mainly hypotension, occurred in 16.3% of the telmisartan group versus 10.7% in the placebo group. CONCLUSIONS: addition of telmisartan to standard therapies significantly reduces all-cause mortality, cardiovascular death, and heart failure hospital stays in hemodialysis patients with CHF and LVEF ≤ 40%. (Effects Of Telmisartan Added To Angiotensin Converting Enzyme Inhibitors On Mortality And Morbidity In Haemodialysed Patients With Chronic Heart Failure: A Double-Blind Placebo-Controlled Trial; NCT00490958).

Is there any survival advantage of obesity in Southern European haemodialysis patients?

BACKGROUND: In the general population, a high body mass index (BMI) is associated with increased cardiovascular disease and all-cause mortality. However, according to US epidemiological evaluation in maintenance haemodialysis (HD) patients, a reverse epidemiology is described and baseline obesity appears paradoxically associated with better survival. The aim of this study is to examine in a Southern European HD population the relationship between survival and BMI at the start of HD treatment, and how survival is influenced by the body weight (BW) variations during the first year of treatment. METHODS: A total of 85 dialysis centres located in Portugal, France and Italy and belonging to the FME European dialysis chain were included. The current prospective analysis focuses on incident patients admitted to these centres between 1 January 2000 and 30 September 2005 with <1 month of previous follow-up on RRT. Data were gained from the FME EuCliD database. Patients were classified at baseline in four categories according to the BMI: underweight, normal range, overweight and obese. Also, the patient survival was analysed according to five quintiles of BW changes during the first year of HD treatment <-5.8%, -5.8 to -1.1%, -1.1 to 1.7% (reference category), +1.7 to +5.5% and >+5.5%. Survival analysis was adjusted for a set of demographic and comorbids using Kaplan-Meier curves and Cox model. Hazard ratios and their 95% confidence intervals were calculated with the use of the estimated regression coefficients and their standard errors. RESULTS: A total of 5592 patients were analysed (40.9% females), and the mean age at admission was 64.4 + 16.5 years. Of them, 27.7% were diabetic. The mean follow-up was 2.0 +/- 1.6 years. Almost half of the patients (46.4%) were in the normal range of BMI (20-24.9 kg/m(2)). When analysed with the Cox model, the categories of baseline BMI (underweight, normal range, overweight and obese) significantly influenced the survival with the respective hazard ratio (HR) and confidence interval at 1.14 (0.96-1.35), 1, 0.74 (0.67-0.9) and 0.78 (0.56-0.87). The strength of the association as well as the shape of the curve remains unchanged after considering age, diabetes and comorbidities. Moreover, when compared to patients for whom BW remained stable during the first year of HD treatment, survival was significantly lower in patients presenting in the lower quintile of BW variation (<-5.8% in 1 year) with an HR of 1.6. CONCLUSIONS: Despite increased comorbidities, overweight and obese patients on maintenance HD carry a significant lower mortality risk than patients in the normal and lower BMI ranges. This confirms the reverse epidemiology previously reported in US HD patients for these categories of BMI. Also BW variation during the first year of HD treatment is associated with patient survival, highlighting the importance of nutrition in this setting.

Heart rate as independent prognostic factor for mortality in normotensive hemodialysed patients.

BACKGROUND: Several epidemiological studies have reported heart rate (HR) as a predictor of cardiovascular and noncardiovascular mortality in the general population. Aim of the present study was to investigate a possible relation between increased HR and mortality in normotensive end-stage renal disease (ERSD) patients. METHODS: Between 1997 and 2001 we recruited 407 normotensive ESRD patients (mean age 56.6 +/- 3.3 years) without coronary artery disease, left ventricular systolic dysfunction or on antiarrhythmic therapy. Baseline electrocardiography (ECG) at rest, 48-hour ambulatory Holter ECG monitoring and standard echocardiography were performed. After a mean follow-up of 46 months (range 12-60 months), cardiovascular and sudden death were considered as end points. RESULTS: Echocardiogram showed a normal left ventricular ejection fraction (>55%) in 370 patients (91%) and left ventricular hypertrophy (LVH) in 290 patients (71.2%). Mean HR by 48-hour Holter ECG was 81 +/- 10.6 bpm. During the follow-up, all-cause mortality rate was 12% (49 patients); 40 patients died from cardiac cause (9.8%) of which 20 patients (4.9%) by sudden death. By univariate analysis, age, diabetes, ECG-LVH with signs of left ventricular strain, and increased mean HR by 48-hour Holter ECG were all significantly related to global, cardiovascular and sudden death. ROC curve analysis identified optimal cutoff points for HR >85 bpm and age >65 years associated with increased cardiovascular risk (p<0.001). By Cox regression analysis, only age >65 years (p<0.0001) and mean HR >85 bpm (p<0.0001) were independent predictors of cardiovascular events. CONCLUSIONS: In normotensive ERSD patients, increased mean HR detected by 48-hour Holter ECG is an independent determinant of global and cardiovascular mortality.

Is it necessary to check outcomes to improve quality of care? The example of anemia management.

The aim of this study was to verify the importance of continuously monitoring the level of adherence to the anemia guideline recommendations in order to improve not only quality of care but also patient safety. Data presented in this investigation were gained through the FME database EuCliD which contains the clinical data of over 24,000 prevalent patients under treatment at the time of the analysis in 344 dialysis centres in 15 countries. Patient data from 4 countries (United Kingdom, Turkey, Italy, Portugal) was used for this study. The parameter selected was anemia control. The level of hemoglobin (Hb) was considered as the quality indicator for anemia, the target being an Hb level >11 g/dL, for UK centres the target was >10 g/dL. All new patients commencing hemodialysis between October 2003 and September 30, 2004 with the previous follow-up of less than one month and without previous blood transfusion were considered. A total of 902 patients were enrolled. The study showed that 4 to 6% of the Italian, Portuguese and British patients treated in FME clinics received a blood transfusion during the first year of follow-up. This is consistent with reports by USRDS that only 3.3% of ESRD patients received at least 1 transfusion per quarter in 1992 after erythropoietin became available and was prescribed to 88% of patients. About 18% Turkish patients, required blood transfusions during the first year of follow-up on hemodialysis, which is more comparable with USRDS data reported in 1989, when 16% of patients needed at least 1 transfusion quarterly. In conclusion, the practice of blood transfusion for hemodialysis patients is still frequent especially in elderly patients.

Assessment of quality guidelines implementation using a continuous quality improvement programme.

BACKGROUND: Data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) study suggest that the level of implementation of the European Best Practice Guidelines (EBPG) is at best partial. The main aim of this study is to describe the level of implementation of the EBPG in the European Fresenius Medical Care (FME) clinic network. METHODS: Data presented in this investigation were gained through the FME database EuCliD (European Clinical Database). Patient data from 4 countries (Great Britain, France, Italy, Spain) were selected from the EuCliD database. The parameters chosen were haemodialysis adequacy, biocompatibility, anaemia control and serum phosphate control, which are surrogate indicators for quality of care. They were compared, by country, between the first quarter (Q1) 2002 and the fourth quarter (Q4) 2005. RESULTS: During Q1 2002 and Q4 2005, respectively, a total of 7,067 and 9,232 patients were treated in FME clinics located in France, Italy, Spain and the UK. This study confirms variations in haemodialysis practices between countries as already described by the DOPPS study. A large proportion of patients in each country achieved the targets recommended by the EBPG in Q4 2005 and this represented a significant improvement over the results achieved in Q1 2002. CONCLUSIONS: Differences in practices between countries still exist. The FME CQI programme allows some of these differences to be overcome leading to an improvement in the quality of the treatment delivered.

Risk factors and underlying cardiovascular diseases in incident ESRD patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in dialysis patients. The aim of this study was to evaluate the prevalence of cardiovascular risk factors and of CVD on admission to hemodialysis. METHODS: Data were collected in 31 Italian clinics belonging to a clinic network using a prospective database (EuCliD), the main purpose of which is the support of quality assurance. Six hundred and thirty-six patients, mean age 63.9+/-15.4 years, admitted between January 1, 2000 and September 30, 2003, were separated into two groups on the basis of presence of CVD and observed for a median follow-up period of 16 months. RESULTS: In the CVD group, patients were significantly older and the percentage of diabetics and smokers was significantly greater than in the CVD-free group. There were no significant differences between the groups in term of uremia-related risk factors. According to logistic regression analysis evaluating the impact of traditional and nontraditional cardiovascular risk factors, only smoking habit (OR 1.87, 95% CI 1.25-2.79) and diabetes (OR 1.87, 95% CI 1.19-2.95) were associated with a higher relative risk for the presence of CVD at baseline. At the time of admission, CVD was present in 27% of patients. The following de novo development of CVD was observed: hypertensive disease (0.28 new cases/100 pt-years), ischemic heart disease (0.71 new cases/100 pt-years), other forms of heart disease (1.57 new cases/100 pt-years), disease of arteries, arterioles, etc. (1.85 new cases/100 pt-years) and cerebrovascular disease (0.71 new cases/100 pt-years). The rate of developing de novo CVD events was 3.70 per 100 patient-years. CONCLUSIONS: The prevalence of cardiovascular risk factors is already high at admission to dialysis. Despite the care provided to dialysis patients, a significant proportion of patients develop de novo CVD.

Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial.

OBJECTIVES: We sought to evaluate the effects of carvedilol on mortality and morbidity in dialysis patients with dilated cardiomyopathy. BACKGROUND: Several lines of evidence support the concept that therapy with beta-blocking agents reduces morbidity and mortality in patients with congestive heart failure (HF), but the demonstration of such a survival benefit in dialysis patients with dilated cardiomyopathy is still lacking. METHODS: A total of 114 dialysis patients with dilated cardiomyopathy were randomized to receive either carvedilol or placebo in addition to standard therapy. A first analysis was performed at one year and was followed by an additional follow-up period of 12 months. RESULTS: Two-year echocardiographic data revealed a significant attenuation of pathologic remodeling, with smaller cavity diameters and higher ejection fractions in the active treatment group than in the placebo group. At two years, 51.7% of the patients died in the carvedilol group, compared with 73.2% in the placebo group (p < 0.01). Furthermore, there were significantly fewer cardiovascular deaths (29.3%) and hospital admissions (34.5%) among patients receiving carvedilol than among those receiving a placebo (67.9% and 58.9%, respectively; p < 0.00001). The exploratory analyses revealed that fatal myocardial infarctions, fatal strokes, and hospital admissions for worsening HF were lower in the carvedilol group than in the placebo group. A reduction in sudden deaths and pump-failure deaths was also observed, though it did not reach statistical significance. CONCLUSIONS: Carvedilol reduced morbidity and mortality in dialysis patients with dilated cardiomyopathy. These data suggest the use of carvedilol in all dialysis patients with chronic HF.

Sustained-release diltiazem reduces myocardial ischemic episodes in end-stage renal disease: a double-blind, randomized, crossover, placebo-controlled trial.

End-stage renal disease (ESRD) patients receiving maintenance hemodialysis and suffering from coronary artery disease (CAD) often receive doses of calcium channel antagonists that are too low. This may be the result of physician's desire to avoid adverse side effects during hemodialysis. The aim of this study was the assessment of the safety and efficacy of incremental doses of diltiazem for the treatment of myocardial ischemia in ERSD patients with CAD to identify the optimal dose of the drug. A total of 196 chronic hemodialysis patients were enrolled with CAD showing more than 5 min of transient myocardial ischemia during a 48-h Holter ECG monitoring. A double-blind, randomized, crossover, placebo-controlled trial design was used. Incremental doses of diltiazem (120 to 240 mg/d) were administered in 4 mo. With a dose of 120 and 180 mg/d, a significant reduction in the number and duration of total and symptomatic ischemic episodes was observed (P < 0.001), but the number and the duration of silent ischemic episodes were not reduced. Conversely, the efficacy on silent myocardial ischemia was obtained with a dosage of diltiazem of 240 mg/d (P < 0.001). In addition, with a sustained-release formulation (120 mg twice daily), the efficacy was similar to that obtained with four 60-mg tablets, but the safety was improved, especially during hemodialytic session. The circadian variations analysis of transient ischemic episodes showed a significant reduction in both ischemic peaks observed at baseline only with 240 mg/d of diltiazem. The findings emphasize that sustained-release diltiazem (120 mg twice daily) can be largely useful in uremic patients with CAD on maintenance dialysis. Diltiazem reduces the number and the duration of silent ischemic episodes, has a good tolerability, and positively modifies the circadian pattern of ischemic episodes.