Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy-five patients undergoing stable dialysis through standard high-flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (ß2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and ß2m RR (r = 0.45, P < 0.001). Time-averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 µmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre- nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as ß2m, could be involved in Hcy RR improvement with HDF.

Fine-tuning of the prediction of mortality in hemodialysis patients by use of cytokine proteomic determination.

BACKGROUND AND OBJECTIVES: Inflammation-induced atherosclerosis and enhanced susceptibility to infection are linked to immune dysfunction and account for an important part of mortality in hemodialysis patients. This 4-yr prospective study aimed to use cytokine proteomic determination for predicting cardiovascular and noncardiovascular mortality in hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Levels of 12 cytokines were measured using a proteomic biochip system in 134 patients who were on stable hemodialysis and compared with a control group of 150 healthy volunteers. Cox proportional hazards regression analysis was used to determine the relationship between cytokine and clinical outcome. RESULTS: A proinflammatory state characterized by decreased anti-/proinflammatory cytokine ratio was evidenced in hemodialysis patients compared with control subjects. After adjustment for age, gender, smoking, and high-sensitivity C-reactive protein levels, IL-6 and (IL-4+IL-10)/IL-6 ratio were associated with a significant and specific enhanced hazard ratio of cardiovascular mortality (hazard ratio 11.32 [95% confidence interval 2.52 to 50.90; P < 0.01] and hazard ratio 3.14 [95% confidence interval 1.20 to 8.22; P < 0.05], respectively, when comparing the third and first tertiles). It is interesting that (IL-4+IL-6+IL-10)/(IL-2+IFN-gamma) ratio, used as a marker of lymphocytes T helper subsets cytokine secretion, was associated only with noncardiovascular mortality (hazard ratio 4.93; 95% confidence interval 1.03 to 23.65; P < 0.05). CONCLUSION: Beyond the strong prediction of cardiovascular mortality by IL-6, determination of cytokine ratios can be useful to identify hemodialysis patients with increased noncardiovascular mortality risk.

Overview of clinical studies in hemodiafiltration: what do we need now ?

Despite several technical advances in dialysis treatment modalities and a better patient care management including correction of anemia, suppression of secondary hyperparathyroidism, lipid and oxidative stress profiles improvement, the morbidity and the mortality of dialysis patients still remain still elevated. Recent prospective interventional trials in hemodialysis (HEMO study and 4D study) were not very conclusive in showing any significant improvement in dialysis patient outcomes. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to conventional diffusive hemodialysis (HD) in improving the dialysis efficacy and in reducing intradialytic morbidity and all-cause and cardiovascular mortality in dialysis patients. The aim of this report was, first, to review the evidence-based facts tending to prove the superiority of HDF vs. HD in terms of efficacy and tolerance, and, second, to analyze the needs to prove the clinical superiority of HDF in terms of reducing morbidity and all-cause mortality of dialysis patients. A systematic review of studies comparing HDF and HD has been performed in the microbiological safety of online production, the solute removal capacity of small and medium-size uremic toxins, and its implication in the reduction of the bioactive dialysis system vs. patient interaction. Major planned randomized international studies comparing HDF and HD in terms of morbidity and mortality have been reviewed. To conclude, it is thought that these long-term prospective randomized trials will clarify on a scientific evidence-based level the putative beneficial role of high-efficiency HDF modalities on dialysis patient outcomes.

Creatinine index and lean body mass are excellent predictors of long-term survival in haemodiafiltration patients.

BACKGROUND: No single measurement adequately defines protein-energy malnutrition. In the dialysis population, somatic protein mass, a useful marker of protein malnutrition, is estimated using the creatinine index (CI), lean body mass (LBM) or both, but the clinical usefulness of these indices remains uncertain. Moreover, calculating these indices requires formal creatinine kinetics or urine and dialysate collection. A simpler method to estimate the creatinine generation rate (G(Cr)) probably might widen its use. METHODS: We evaluated the usefulness of creatinine-based indices for predicting mortality in a cohort of 226 French haemodiafiltration patients using the Cox proportional hazards method. We also proposed simple yet precise formulas to calculate post-dialysis creatinine (Cr(post)) concentrations and derive creatinine generation rates (G(Cr)) from readily available measures. These formulas were developed using a large database containing more than 10 000 measured Cr(post) and G(Cr) values based on formal creatinine modelling. A single set of monthly values was used to evaluate the validity of the formulas. RESULTS: When adjusted for comorbidities, sex and Kt/V, CI and LBM/body weight (LBM/BW) were better predictors of 5 year all-cause mortality than urea-based indices [survival relative risk (RR) = 0.24, P<0.01 for CI<22 mg/kg/day; RR = 0.33, P<0.02 for LBM/BW<0.75]. When the cohort was divided according to gender, similar results were found in males, but not in females. The different formulas allowed adequate prediction of Cr(post) and G(Cr) and classification of patients with good accuracy (CI<22: sensitivity = 94%, specificity = 82%; LBW/BW<0.75: sensitivity = 89%, specificity = 90%). CONCLUSIONS: In a haemodiafiltration population, CI and LBM are excellent predictors of long-term survival. In anuric Caucasian haemodialysis patients, CI and LBM can be estimated from biochemical and anthropometric measurements without relying on formal modelling.

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.