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.

Season affects body composition and estimation of fluid overload in haemodialysis patients: variations in body composition; a survey from the European MONDO database.

BACKGROUND: Seasonal variations in blood pressure (BP) and inter-dialytic weight gain (IDWG) are well established in dialysis patients. However, no study has assessed changes in body composition (BC) in this population. METHODS: In this survey, seasonal variations in fat mass (FM), lean tissue mass (LTM), extracellular water (ECW) and fluid overload (FO) were assessed in 42 099 dialysis patients (mean age 61.2 years, 58% males) from the Fresenius Medical Care Europe database, as part of the MONitoring Dialysis Outcomes (MONDO) consortium, in relation to other nutritional parameters, IDWG and BP. BC was assessed by a body composition monitor (BCM®, Fresenius Medical Care, Bad Homburg, Germany). RESULTS: FM was highest in winter and lowest in summer (▵FM -1.17 kg; P < 0.001), whereas LTM was lowest during winter and highest in summer (▵LTM 0.86 kg; P < 0.0001). ECW and FO were lowest in winter, and highest in spring (▵ECW: 0.13 L; P < 0.0001, ▵FO: 0.31 L; P < 0.0001) and summer (▵ECW: 0.15 L; P < 0.0001 and ▵FO: 0.2 L; P < 0.0001), despite a higher systolic blood pressure (SBP; 136.7 ± 17.4 mmHg) and IDWG (3.0 ± 1.1 kg) during winter. C-reactive protein (CRP), serum sodium and haemoglobin levels were highest in winter, whereas serum albumin was lowest in fall. Normalized protein catabolic rate (nPCR) was lowest in winter and matched variations in BC only to a minor degree. CONCLUSIONS: BC and hydration state, assessed by bio-impedance spectroscopy, follows a seasonal pattern which may be of relevance for the estimation of target weight, and for the interpretation of longitudinal studies including estimates of BC. Whether these changes should lead to therapeutic interventions could be the focus of future studies.

Cannulation technique influences arteriovenous fistula and graft survival.

Hemodialysis patient survival is dependent on the availability of a reliable vascular access. In clinical practice, procedures for vascular access cannulation vary from clinic to clinic. We investigated the impact of cannulation technique on arteriovenous fistula and graft survival. Based on an April 2009 cross-sectional survey of vascular access cannulation practices in 171 dialysis units, a cohort of patients with corresponding vascular access survival information was selected for follow-up ending March 2012. Of the 10,807 patients enrolled in the original survey, access survival data were available for 7058 patients from nine countries. Of these, 90.6% had an arteriovenous fistula and 9.4% arteriovenous graft. Access needling was by area technique for 65.8%, rope-ladder for 28.2%, and buttonhole for 6%. The most common direction of puncture was antegrade with bevel up (43.1%). A Cox regression model was applied, adjusted for within-country effects, and defining as events the need for creation of a new vascular access. Area cannulation was associated with a significantly higher risk of access failure than rope-ladder or buttonhole. Retrograde direction of the arterial needle with bevel down was also associated with an increased failure risk. Patient application of pressure during cannulation appeared more favorable for vascular access longevity than not applying pressure or using a tourniquet. The higher risk of failure associated with venous pressures under 100 or over 150 mm Hg should open a discussion on limits currently considered acceptable.

Interdialytic weight gain, systolic blood pressure, serum albumin, and C-reactive protein levels change in chronic dialysis patients prior to death.

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

Monitoring dialysis outcomes across the world--the MONDO Global Database Consortium.

BACKGROUND/AIMS: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. METHODS: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. RESULTS: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. CONCLUSION: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

Converting to a capitation system for dialysis payment--the Portuguese experience.

Due to the challenge of operating within an economically strained healthcare budget, Portuguese health authorities convened with dialysis providers and agreed on a framework to change from a fee-for-service reimbursement modality to a capitation payment system for hemodialysis. This article reviews the components of the agreed capitation package implemented in 2008 as well as the necessary preparatory work undertaken by a for-profit 34-unit dialysis network (approx. 4,200 patients) to cope with the introduction of this system. Furthermore, trends in clinical quality indicators and in resource management are reviewed for 3 years immediately following capitation introduction. Here, improvements were observed over time for the specified clinical targets. Simultaneously, costs controllable by the physician could be reduced. As more countries convert to a capitation or bundled payment system for hemodialysis services, this article offers insight into the scope of the necessary preparatory work and the possible consequences in terms of costs and treatment quality.

Delivering quality of care while managing the interests of all stakeholders.

National healthcare systems worldwide face growing challenges to reconcile interests of patients for high-quality medical care and of payers for sustainable and affordable funding. Advances in the provision of renal replacement therapy can only be made by developing and implementing appropriate sophisticated and state-of-the-art business models that include reimbursement schemes for comprehensive care packages. Such business models must succeed in integrating and reconciling the interests of all stakeholders. NephroCare as dialysis provider has adopted and tailored recognized management techniques, i.e. Balanced Scorecard and Kaizen, to achieve these goals. Success of the complete business model package is tangible - strategies initiated to improve treatment quality even at the cost of providers have been translated into win-win scenarios for the complete stakeholder community. Room for improvement exists: the possibility to extend the portfolio of service offerings within the comprehensive care frame, as well as the challenge for achieving a balance between the stability of targets while keeping these up to date concerning new insights.

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.

Improved survival of incident patients with high-volume haemodiafiltration: a propensity-matched cohort study with inverse probability of censoring weighting.

BACKGROUND: Haemodiafiltration (HDF) is the preferred dialysis modality in many countries. The aim of the study was to compare the survival of incident patients on high-volume HDF (HV-HDF) with high-flux haemodialysis (HD) in a large-scale European dialysis population. METHODS: The study population was extracted from 47,979 patients in 369 NephroCare centres throughout 12 countries. Baseline was six months after dialysis initiation; maximum follow-up was 5 years. Patients were either on HV-HDF (defined as with ≥21 litres substitution fluid volume per session) or on HD if on that treatment for ≥75% of the 3 months before baseline. The main predictor was treatment modality. Other parameters included country, age, gender, BMI, haemoglobin, albumin and Charlson comorbidity index. Propensity score matching and Inverse Probability of Censoring Weighting (IPCW) were applied to reduce bias by indication and consider modality crossover, respectively. RESULTS: After propensity score matching, 1,590 incident patients remained. Kaplan-Meier and proportional Cox regression analyses revealed no significant survival advantage of HV-HDF. Results were biased by modality crossover: during the 5-year study period, 7% of HV-HDF patients switched to HD, and 55% of HD patients switched to HV-HDF. IPCW uncovered a statistically significant survival advantage of HV-HDF (OR 0.501; CI 0.366-0.684; p < 0.001). A higher benefit of HV-HDF for some subgroups was revealed, for example, non-diabetics, patients 65-74 years, patients with obesity or high blood pressure. CONCLUSIONS: This large-scale study supports the generalizability of previous RCT findings regarding the survival benefit of HV-HDF. Sub-group analysis showed that some sub-cohorts appear to benefit more from HV-HDF than others.

Body composition and survival in dialysis patients: results from an international cohort study.

BACKGROUND AND OBJECTIVES: High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data between April 2006 and December 2012 were extracted from the Fresenius Medical Care Europe subset of the international MONitoring Dialysis Outcomes initiative. Fresenius Medical Care Europe archives a unique repository of predialysis body composition measurements determined by multifrequency bioimpedance (BCM Body Composition Monitor). The BCM Body Composition Monitor reports lean tissue indices (LTIs) and fat tissue indices (FTIs), which are the respective tissue masses normalized to height squared, relative to an age- and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression. RESULTS: In 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m(2), respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P<0.001). Survival was best with LTI between 15 and 20 kg/m(2) and FTI between 4 and 15 kg/m(2) (probability of death during follow-up: <5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P<0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P<0.001 at low LTI-high FTI). CONCLUSIONS: This large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.

Relationship of Neutrophil-to-Lymphocyte Ratio and Serum Albumin Levels with C-Reactive Protein in Hemodialysis Patients: Results from 2 International Cohort Studies.

BACKGROUND/AIM: The neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients. METHODS: We analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (<2.5, 2.5-5 and >5.0) and albumin levels (<3.1, 3.1-4.0 and >4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort. RESULTS: We found that NLR >5.0 vs. <2.5 (cohort 1: OR 2.3; p < 0.0001 and cohort 2: OR 2.0; p < 0.0001) was associated with CRP levels >10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin <3.1) (cohort 1: OR 7.6; p < 0.0001 and cohort 2: OR 11.9; p < 0.0001). Cross-validation of the 2 regression models revealed a predictive accuracy of 0.68 and 0.69 in the respective cohorts. CONCLUSION: This study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.

Survival of incident patients on high-volume online hemodiafiltration compared to low-volume online hemodiafiltration and high-flux hemodialysis.

BACKGROUND: Hemodiafiltration is becoming a preferred treatment modality for dialysis patients in many countries. The volume of substitution fluid delivered has been indicated as an independent mortality risk factor. The aim of this study is to compare patient survival on three different treatment modalities: high-flux hemodialysis, low-volume online HDF (oHDF) and high-volume oHDF. METHODS: Incident hemodialysis and oHDF patients treated in 13 NephroCare centers in Bosnia and Herzegovina, Serbia and Slovenia between January 1, 2007, and December 31, 2011, were included in this epidemiological cohort study. High-volume oHDF was defined as substitution volume higher than the median substitution volume infused, otherwise low-volume. Main predictor was treatment modality at baseline and in time-dependent model. Other predictors were age, gender, diabetes mellitus, cerebrovascular accident, arrhythmia, hemoglobin and C-reactive protein. RESULTS: Four hundred and forty-two patients were included in the study. Median substitution fluid volume was 20.4 L. Mean difference between the oHDF groups in substitution fluid volume was 8.3 ± 5.2 L [95 % confidence intervals (95 % CI) 7.1-9.5, p < 0.0001]. The unadjusted hazard ratios (HR) with 95 % CI compared to high-flux HD were 0.87 (0.5-1.5) for low-volume oHDF and 0.29 (0.13-0.63) for high-volume oHDF. After the adjustment for covariates, the HR for patients on low-volume oHDF remained statistically insignificant compared to high-flux HD (0.84; 95 % CI 0.46-1.53), while patients on high-volume oHDF showed a marked and significantly lower HR (0.29; 95 % CI 0.13-0.68) than patients on high-flux HD in baseline model. While this effect failed to reach significance in the time-dependent model (HR 0.477; 95 % CI 0.196-1.161), possibly due to an inadequate sample size here, the consistency of results in both models supports the robustness of the findings. After switching from high-flux hemodialysis to oHDF, mean hemoglobin and albumin levels did not change significantly. Mean erythropoietin resistance index (ERI) and erythropoiesis stimulating agents (ESA) consumption decreased significantly (p = 0.02, p = 0.03, respectively). CONCLUSIONS: The median substitution volume used in these three countries for post-dilutional oHDF is 20.4 L. oHDF is associated with significant reductions in ERI and ESA consumption. Only high-volume oHDF is associated with improved survival compared to high-flux hemodialysis.

Adopting on-line hemodiafiltration as standard therapy in EMEA NephroCare centers.

This paper describes the historical journey that led to the adoption of on-line hemodiafiltration (HDF) as a standard therapy for the patients in the Fresenius Medical Care (FME) NephroCare dialysis network. In 1998, FME faced the tremendous challenge of consolidating a series of heterogeneous clinics under one umbrella. In 2002, the European Best Practice Guidelines (EBPG) for hemodialysis (HD) were published by the European Renal Association which FME promptly adopted within its clinic network. On the basis of this document, the strategic decision was taken to apply high-flux, biocompatible membranes throughout the entire network. To cope with the effective implementation of this step, the clinics' technical infrastructure was updated. The widespread application of high-flux therapy, together with the implementation of the required infrastructure, especially concerning water quality, opened the way to the extensive use of on-line HDF. To fully realize this ambitious goal, two further technological steps were targeted and successfully reached: introduction of the Fresenius 5008 dialysis equipment and an even stricter control of the water quality. The combined pressure from the educational activities, which brought about a preliminary cultural change, and the creation of a target based on the percentage of treatments by this technique resulted in an increasing implementation of this modality by the individual clinics. After 2004, on-line HDF continuously increased its share among the dialysis techniques prescribed in the network and currently more than 50% of patients are on this modality.

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.