Impact of fluid status and inflammation and their interaction on survival: a study in an international hemodialysis patient cohort.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

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.

High-volume postdilution hemodiafiltration is a feasible option in routine clinical practice.

Hemodiafiltration (HDF) with 20-22 L of substitution fluid is increasingly recognized as associated with significant benefits regarding patient outcome. However, some doubt exists as to whether these high volumes can be achieved in routine clinical practice. A total of 4176 sessions with 366 patients on postdilution HDF were analyzed in this 1-month observational cohort study with prospective data collection. All dialysis machines were equipped with AutoSub plus signal analysis software that automatically and continuously adapts the substitution fluid flow according to the blood flow, blood viscosity, and dialyzer characteristics. Percentages of sessions with different types of vascular access were compared regarding achievement of ≥21 L substitution fluid. Logistic regression analysis was conducted to study the independent relationship of selected variables with achievement of ≥21 L substitution volume. Patient- and dialysis-related variables that showed an association with the convection volume were entered in a multivariable model that included hematocrit up front. Respectively, 87%, 84%, and 33% of routine sessions conducted with fistulas, grafts, and catheters qualified as high-volume HDF. Serum albumin levels ≥4.2 g/dL were positively associated with the achievement of at least 21 L substitution volume. Positive associations were also observed for blood flows in the ranges 350-399 and ≥400 mL/min compared with the reference range (300-350 mL/min), for longer treatment time, for fistula versus catheter, for higher filtration fraction, and for dialysis conducted at the end of the week versus Monday. It can be concluded that implementation and sustainability of high-volume HDF is possible in routine clinical practice for almost all patients treated with fistulas and grafts.

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.

Impact of targeting Kt instead of Kt/V.

BACKGROUND: Patients must receive an adequate dialysis dose in each hemodialysis (HD) session. Ionic dialysance (ID) enables the dialysis dose to be monitored in each session. The aim of this study was to compare the achievement of Kt versus eKt/V values and to analyse the main impediments to reaching the dialysis dose. METHODS: Of 5316 patients from 54 Fresenius Medical Care centers in Spain undergoing their usual HD regime, 3275 received ID and were included in the study. RESULTS: The minimum prescribed dose of eKt/V was reached in 91.2% of the patients, while the minimum recommended dose of Kt was reached in only 66.8%. Patients not receiving the minimum Kt dose were older, had spent 7 months less on dialysis, had a dialysis duration of 6 min less, had 5.7 kg more of body weight and Qb was 47 mL/min lower. The target Kt was not reached by 62% of patients with catheters and by 37% of women. With each quintile increase of body weight, eKt/V decreased and Kt increased. Of patients with a body weight >80 kg, 1.4%, mostly men, reached the target Kt but not prescribed eKt/V. CONCLUSIONS: The impact of monitoring the dose with Kt instead of Kt/V is that identifies 25.8% of patients who did not reach the minimum Kt while achieving Kt/V. The main impediments to achieving an adequate dialysis dose were catheter use, female sex, advanced age, greater body weight, shorter dialysis time and lower Qb.

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.

Elements of dialysis nursing practice associated with successful cannulation: result of an international survey.

BACKGROUND/AIM: Vascular access (VA) cannulation is an essential skill for dialysis nurses: failure to correctly repeat this operation daily may result in serious complications for the patients. This study investigates if different aspects of arteriovenous fistula and graft cannulation have an effect on the development of acute access complications, which may affect the VA survival. METHODS: In April 2009 a cross-sectional survey was conducted in 171 dialysis units located in Europe, the Middle East and Africa to collect details on VA cannulation practices. Information on cannulation retrieved from the survey comprised fistula type and location, cannulation technique, needle size, use of disinfectants and of local anaesthetics, application of arm compression at the time of cannulation, needle and bevel direction, needle rotation, and needle fixation. Five categories of complications were investigated: multiple-cannulation, infiltration, haematoma, haemorrhage and unknown. RESULTS: There were 10,807 cannulation procedures evaluated in the same number of patients. Of these, 367 showed some kind of complication, the most frequent (33.8%) being the need for multiple-cannulation. The following were associated with a significantly higher odds ratio for occurrence of an acute complication: prescription of back-eye needles, use of rope-ladder cannulation technique, insertion of venous needle as first needle, and rotation of the arterial needle. Use of 16-17-gauge needles was also significantly associated with complications, but this possibly reflects poor quality of the VA. CONCLUSIONS: The risk of an acute VA complication could be reduced with appropriate training of nurses, physicians and patients. This could potentially prolong the VA life.

Comparison of Turkish and US haemodialysis patient mortality rates: an observational cohort study.

BACKGROUND: There are significant differences between countries in the mortality rates of haemodialysis (HD) patients. The extent of these differences and possible contributing factors are worthy of investigation. METHODS: As of March 2009, all patients undergoing HD or haemodiafiltration for >3 months (n = 4041) in the Turkish clinics of the NephroCare network were enrolled. Data were prospectively collected for 2 years through the European Clinical Dialysis Database. Mean age ± standard deviation was 58.7 ± 14.7 years, 45.9% were female and 22.9% were diabetic. Comparison with US data was performed by applying an indirect standardization technique, using specific mortality rates for patients on HD by age, gender, race and primary diagnosis as provided by the 2012 US Renal Data System Annual Data Report as reference. RESULTS: The crude mortality rate in Turkey was 95.1 per 1000 patient-years. Compared with the US reference population, the annual mortality rate for Turkey was significantly lower, irrespective of gender, age and diabetes. After adjustments for age, gender and diabetes, the mortality risk in the Turkish cohort was 50% lower than US whites [95% confidence interval (CI) 0.46-0.54, P < 0.001], 44% lower than US African-Americans (95% CI 0.52-0.61, P < 0.001) and 20% lower than Asian-Americans (95% CI 0.74-0.86, P < 0.05). CONCLUSIONS: The annual mortality rate of prevalent HD patients was found to be significantly lower in the studied Turkish cohort compared with that published by the US Renal Data System Annual Data Report. Differences in practice patterns may contribute to the divergence.

Does the extracorporeal blood flow affect survival of the arteriovenous vascular access?

Hemodiafiltration with high-convective volumes is associated with improved patient survival, whereby practical realization is contingent on high extracorporeal blood flow (Qb) and dialysis treatment time. However, Qb is restricted by vascular access (VA) quality and/or concerns that high Qb could damage the VA. Taking VA quality into consideration, one can investigate the relationship between Qb and VA survival. We analyzed data from 1039 patients treated by hemodiafiltration over a 21-month period where access blood flow (Qa) measurements were also available at baseline. VA failure was defined as a surgical intervention resulting in the generation of a new VA. Qa was included as a stratification variable within a Cox regression model. A second Cox proportional hazard model with a penalized spline was used to describe the association between Qb and VA survival. Compared with Qb in the 350-357 mL/min range, a significantly higher hazard ratio (HR) for VA failure was detected for fistula only, and then only for Qb < 312 mL/min (HR: 2.361, 95% confidence interval [CI]: 1.251-4.453), Qb = 387-397 mL/min (HR: 1.920, 95% CI: 1.007-3.660) and Qb >414 mL/min (HR: 2.207, 95% CI: 1.101-4.424). Age, gender, diabetes, VA vintage, position of the VA, and arterial pressure were not significantly associated with outcome. The form of the penalized spline confirmed higher risk for VA failure for the lowest and the highest values of Qb. Taking Qa into consideration, no association was found between VA failure and Qb up to flows as high as approximately 390 mL/min.

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.

Effect of Membrane Permeability on Cardiovascular Risk Factors and ß2m Plasma Levels in Patients on Long-Term Haemodialysis: A Randomised Crossover Trial.

Survival of haemodialysis (HD) patients is influenced by many factors. Mortality is mainly of cardiovascular (CV) origin and related to both traditional and nontraditional CV risk factors. Low plasma Beta2-microglobulin (ß2m) levels are associated with improved HD patient survival. HD session times that are longer than the conventional 4 h (i.e., extended dialysis) provide better middle molecule clearance and are also associated with a survival advantage. In this crossover randomised trial, we investigated the effect of membrane flux on CV risk factors and on ß2m plasma levels in patients treated with extended dialysis. Dialysis session duration was between 5 and 8 h for all patients. Patients were randomly assigned to the treatment sequences low-flux/high-flux dialysis versus high-flux/low-flux dialysis in a crossover design after a 3-month run-in period, with each phase lasting 9 months. Of the initially enrolled 168 patients, 155 patients started the study after the run-in period, 117 patients completed Phase 1, and 83 patients completed the whole study. Lp(a), homocystein, LDL cholesterol, HDL cholesterol and serum albumin were comparable in the low-flux and high-flux treatments. The average ß2m level was 43.3 ± 11.1 mg/l at the end of the low-flux phase. Independent of sequence assignation, average ß2m was significantly lower at the end of the high-flux phase (27.5 ± 76.0 mg/l, p < 0.0001 versus end of low-flux phase). Both phosphate and nPNA were significantly lower at the end of the high-flux phase compared to the low-flux phase (p = 0.045 and p = 0.002, respectively). Inclusion of those patients who completed Phase 1 and who dropped out of the study during Phase 2 did not significantly change the results. In conclusion, this study did not find an influence of high-flux filters on several traditional CV risk factors in a population of HD patients treated with extended dialysis. However, high-flux filters are necessary to optimise middle molecule clearance and reduce the ß2m level.

The forgotten role of central volume in low frequency oscillations of heart rate variability.

The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations.

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.

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.