Renée Lévesque

Effect of Online Hemodiafiltration on All-Cause Mortality and Cardiovascular Outcomes

In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.

Short-term Effects of Online Hemodiafiltration on Phosphate Control: A Result From the Randomized Controlled Convective Transport Study (CONTRAST)

BACKGROUND Hyperphosphatemia is an independent risk factor for all-cause and cardiovascular mortality in hemodialysis (HD) patients. Phosphate control often is unsuccessful using conventional dialysis therapies. STUDY DESIGN Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. SETTING & PARTICIPANTS 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. INTERVENTION Online hemodiafiltration (HDF) versus continuation of low-flux HD. OUTCOMES Differences in change from baseline to 6 months in phosphate levels and proportion of patients reaching phosphate treatment targets (phosphate < or = 5.5 mg/dL). MEASUREMENTS Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. RESULTS Phosphate levels decreased from 5.18 +/- 0.10 (SE) mg/dL at baseline to 4.87 +/- 0.10 mg/dL at 6 months in HDF patients (P < 0.001) and were stable in HD patients (5.10 +/- 0.10 mg/dL at baseline and 5.03 +/- 0.10 mg/dL after 6 months; P = 0.5). The difference in change in phosphate levels between HD and HDF patients (B = -0.24; 95% CI, -0.52 to 0.03; P = 0.08) increased after adjustment for phosphate-binder use (B = -0.36; 95% CI, -0.65 to -0.06; P = 0.02). The proportion of patients reaching phosphate treatment targets increased from 64% to 74% in HDF patients and was stable in HD patients (66% and 66%); the difference between groups reached statistical significance (P = 0.04). Nutritional parameters and residual renal function were similar in both treatment groups. LIMITATIONS Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. CONCLUSION HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established.

Role of Residual Renal Function in Phosphate Control and Anemia Management in Chronic Hemodialysis Patients

BACKGROUND AND OBJECTIVES There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output≥100 ml/24 h (n=295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output<100 ml/24 h, n=274). Relations between GFR and serum phosphate and erythropoiesis-stimulating agent (ESA) index (weekly ESA dose per kg body weight divided by hematocrit) were analyzed with multivariable regression models. RESULTS Phosphate levels were between 3.5 and 5.5 mg/dl in 68% of patients in the upper tertile (GFR>4.13 ml/min per 1.73 m2), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9±1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients. CONCLUSIONS This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged.

Role of Residual Kidney Function and Convective Volume on Change in β2-Microglobulin Levels in Hemodiafiltration Patients

BACKGROUND AND OBJECTIVES Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models. RESULTS Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume. CONCLUSIONS This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.

Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis

Online hemodiafiltration may diminish inflammatory activity through amelioration of the uremic milieu. However, impurities in water quality might provoke inflammatory responses. We therefore compared the long-term effect of low-flux hemodialysis to hemodiafiltration on the systemic inflammatory activity in a randomized controlled trial. High-sensitivity C-reactive protein and interleukin-6 were measured for up to 3 years in 405 patients of the CONvective TRAnsport STudy, and albumin was measured at baseline and every 3 months in 714 patients during the entire follow-up. Differences in the rate of change over time of C-reactive protein, interleukin-6, and albumin were compared between the two treatment arms. C-reactive protein and interleukin-6 concentrations increased in patients treated with hemodialysis, and remained stable in patients treated with hemodiafiltration. There was a statistically significant difference in rate of change between the groups after adjustments for baseline variables (C-reactive protein difference 20%/year and interleukin-6 difference 16%/year). The difference was more pronounced in anuric patients. Serum albumin decreased significantly in both treatment arms, with no difference between the groups. Thus, long-term hemodiafiltration with ultrapure dialysate seems to reduce inflammatory activity over time compared to hemodialysis, but does not affect the rate of change in albumin.

Patient- and treatment-related determinants of convective volume in post-dilution haemodiafiltration in clinical practice

BACKGROUND Large convective volumes are recommended for online haemodiafiltration (HDF) to maximize solute removal. There has been little systematic evaluation of factors that determine convective volumes in routine clinical practice. METHODS In the present study, potential patient- and treatment-related determinants of convective volume were analysed in 235 consecutive patients on post-dilution HDF using multivariable linear regression models. All patients (age 64 +/- 14 years; 61% male) participated in the ongoing CONvective TRAnsport STudy (CONTRAST). Additionally, differences in convective volumes between dialysers were evaluated. RESULTS The mean convective volume was 19.4 +/- 4.0 L (+/-SD) per treatment, with a large variation between the participating centres (centre means ranging from 13.4 +/- 0.9 L to 24.5 +/- 0.12 L, +/- SE). The mean filtration fraction of the blood flow was 25.9 +/- 3.6. In the multivariable analysis, factors that were significantly related to convective volume were haematocrit [inversely, regression coefficient (B) = -1.4 +/- 0.4 L per 10%], serum albumin (positively, B = 1.0 +/- 0.4 L per 10 g/L), blood flow rate (positively, B = 0.4 +/- 0.04 L per 10 mL/min) and treatment time (positively, B = 5.1 +/- 0.4 L/h). In addition, significant differences between dialysers were observed, likely explained by different operational conditions. CONCLUSIONS Apart from increasing the treatment time and blood flow rate, convective volumes could be optimized by increasing the filtration fraction in each individual, provided that transmembrane pressures are well within safe limits. The precise role of dialyser characteristics on maximal achievable convective volumes in clinical practice is a topic for further research.

Effect of Hemodiafiltration on Quality of Life over Time

BACKGROUND AND OBJECTIVES It is unclear if hemodiafiltration leads to a better quality of life compared with hemodialysis. It was, therefore, the aim of this study to assess the effect of hemodiafiltration on quality of life compared with hemodialysis in patients with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study analyzed the data of 714 patients with a median follow-up of 2 years from the Convective Transport Study. The patients were enrolled between June of 2004 and December of 2009. The Convective Transport Study is a randomized controlled trial on the effect of online hemodiafiltration versus low-flux hemodialysis on all-cause mortality. Quality of life was assessed with the Kidney Disease Quality of Life-Short Form. This questionnaire provides data for a physical and mental composite score and describes kidney disease-specific quality of life in 12 domains. The domains have scales from 0 to 100. RESULTS There were no significant differences in changes in health-related quality of life over time between patients treated with hemodialysis (n=358) or hemodiafiltration (n=356). The quality of life domain patient satisfaction declined over time in both dialysis modalities (hemodialysis: -2.5/yr, -3.4 to -1.5, P<0.001; hemodiafiltration: -1.4/yr, -2.4 to -0.5, P=0.004). CONCLUSIONS Compared with hemodialysis, hemodiafiltration had no significant effect on quality of life over time.

Treatment policy rather than patient characteristics determines convection volume in online post-dilution hemodiafiltration.

Background/Aims: Sub-analyses of three large trials showed that hemodiafiltration (HDF) patients who achieved the highest convection volumes had the lowest mortality risk. The aims of this study were (1) to identify determinants of convection volume and (2) to assess whether differences exist between patients achieving high and low volumes. Methods: HDF patients from the CONvective TRAnsport STudy (CONTRAST) with a complete dataset at 6 months (314 out of a total of 358) were included in this post hoc analysis. Determinants of convection volume were identified by regression analysis. Results: Treatment time, blood flow rate, dialysis vintage, serum albumin and hematocrit were independently related. Neither vascular access nor dialyzer characteristics showed any relation with convection volume. Except for some variation in body size, patient characteristics did not differ across tertiles of convection volume. Conclusion: Treatment time and blood flow rate are major determinants of convection volume. Hence, its magnitude depends on center policy rather than individualized patient prescription.

On-Line Hemodiafiltration as Routine Treatment of End-Stage Renal Failure: Why Pre- or Mixed Dilution Mode Is Necessary in On-Line Hemodiafiltration Today?

Hemodiafiltration (HDF) is a well-recognized treatment modality that offers a way of optimizing renal replacement therapy efficacy of end-stage renal disease (ESRD) patients. On-line production of substitution fluid by the ‘cold sterilization’ process (ultrafiltration) gives access to an unlimited amount of sterile and non-pyrogenic IV grade solution. This advantageous low-cost solution may therefore be employed to develop various forms of high-flux HDF modalities (ol-HDF). High-flux post-dilutional HDF (post-HDF) has mainly been used in clinical practice since it offers the most efficient and best compromise between diffusive and convective clearances. Nowadays, the new targets in anemia correction have created hemorheological conditions that render high filtration rate more difficult to achieve and/or at the expense of higher transmembrane pressure. To overcome this new challenging condition and keeping the same concept, it has been proposed to develop alternative modalities with various sites of fluid substitution (predilution, mixed pre-post with various percentages) in HDF. In this presentation we discuss the benefits of using pre-HDF and show how to match performances with post-HDF. Potential advantages of new ol-HDF options (pre-, mixed and mid-dilution) that are advocated have to be demonstrated in clinical trials. On-line HDF is a multipurpose treatment method that is employed to improve care and outcomes of ESRD patients. Due to its versatility, ol-HDF should be considered as a technical platform permitting to personalize and tailor treatment to patients’ needs. The mode of substitution (post-, pre-, mixed or mid-dilution) should be established according to hemorheological conditions of the individual patient.

Protein-Energy Nutritional Status and Kidney Disease-specific Quality of Life in Hemodialysis Patients

OBJECTIVE Health-related quality of life (HRQOL) is an important outcome in dialysis care. Previous research has related protein-energy nutritional status to generic HRQOL domains, but it is still not clear as to how it relates to HRQOL domains that are unique to hemodialysis patients. Therefore, our aim was to study the relation between protein-energy nutritional status and kidney disease-specific HRQOL domains in hemodialysis patients. DESIGN This was a cross-sectional study. SETTING This study was performed at multiple centers. PATIENTS OR OTHER PARTICIPANTS We evaluated the first 590 hemodialysis patients who had enrolled in the Convective Transport Study. DETERMINANTS We measured protein-energy nutritional status by using the Subjective Global Assessment, albumin, normalized nitrogen appearance, creatinine, body mass index, and cholesterol. MAIN OUTCOME MEASURE HRQOL was assessed by using the Kidney Disease Quality Of Life-Short Form. RESULTS In all, 83% of the cohort was found to be well-nourished on the basis of the Subjective Global Assessment. Multiple nutritional parameters were positively related to the physical summary of generic HRQOL and to the following kidney disease-specific HRQOL scales: the effects of the kidney disease on daily life, the burden of the kidney disease, and overall health. CONCLUSIONS This study showed that, even in predominantly well-nourished hemodialysis patients, protein-energy nutritional status was significantly related to kidney disease-specific HRQOL.