On-line Haemofiltration Research Articles

Phosphate levels in patients treated with low-flux haemodialysis, pre-dilution haemofiltration and haemodiafiltration: post hoc analysis of a multicentre, randomized and controlled trial

Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial. This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients). CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P < 0.001) and sevelamer (P < 0.001), pre-dialysis bicarbonate levels (P < 0.001) and pre-dialysis blood K levels (P < 0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P < 0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P. In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309).

Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial

BackgroundPredictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes.MethodsPrimary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients).ResultsCTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta2 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta2 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170).ConclusionsIn comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

Intermittent high-volume predilution on-line haemofiltration versus standard intermittent haemodialysis in critically ill patients with acute kidney injury: a prospective randomized study

The optimal modality of dialysis treatment in critically ill patients with acute kidney injury (AKI) remains unclear. Intermittent high-volume predilution on-line haemofiltration (HF) is not a well-established dialysis modality. The purpose of the study was to compare clinical outcomes between HF and standard intermittent haemodialysis (HD) in this specific population. In this prospective, randomized, controlled single-centre clinical study, we compared mortality and recovery of kidney function between HF and HD in critically ill adult patients with AKI. The primary study outcome was 60-day all-cause mortality. Secondary study outcomes included 30-day and in-hospital all-cause mortality along with recovery of kidney function. Time to kidney function recovery and the number of required dialysis procedures were analyzed in the subgroup of patients with in-hospital recovery of kidney function. Baseline characteristics of the 273 patients in the two study groups were similar. All-cause mortality by Day 60 was 65.0% in the HF group and 65.5% in the HD group (hazard ratio, 0.98; 95% confidence interval, 0.71-1.33; P = 0.87). There were also no significant differences between the two groups in 30-day and in-hospital all-cause mortality or recovery of kidney function. Time to kidney function recovery and the number of required dialysis procedures were similar between the HF and the HD subgroup of patients with in-hospital recovery of kidney function. Dialysis treatment with intermittent high-volume predilution on-line HF in critically ill patients with AKI did not decrease mortality, improve recovery of kidney function or reduce the need for dialysis support compared to standard intermittent HD.

Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study

Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF). The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized. After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change. No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state.

Thermal balance in convective therapies.

Among the factors causing intradialytic haemodynamic instability, dialysate temperature has been shown to play a relevant role. An improved cardiovascular response during isolated ultrafiltration or with cooled dialysate has been described in the past. Cold dialysate may increase the external heat loss compensating for the increase in core temperature, thus avoiding vasodilatation, but it also increases myocardial contractility. However, a better haemodynamic response to dialysis treatment has long been known in convective therapies as well, and the hypothesis of a leading role for thermal balance is under discussion. In conventional haemofiltration (HF), venous blood cooling is expected, on the basis of the infusate temperature and the filtration fraction. In on-line HF, the infusate temperature and its volume may have a different impact on thermal balance depending on the site of infusion (pre- or post-dialyser). In an in vitro study comparing haemodialysis (HD) (conventional HD, dialysate 37 degrees C; and cold HD, dialysate 35.5 degrees C) with HF (pre- and post-dilution, 37 degrees C), we observed a more negative thermal balance with cold HD (-130 kJ/h) and with post-dilution HF (-75 kJ/h). The beneficial pressor effects of HF have been confirmed even in on-line HF, which actually has very few differences in the thermal balance compared with conventional HD (dialysate 37 degrees C). In on-line HF, the amount of warm infusion, often exceeding the blood flow, makes the achievement of a negative thermal balance highly unlikely. Thus, there is not sufficient evidence that vascular stability in on-line HF is solely related to different thermal energy balances. Other factors playing a relevant role in the cardiocirculatory response to convective dialysis should thus be considered.

Optimizing dose and mode of renal replacement therapy in anaemia management.

Iron supplementation is probably the most important factor affecting response to treatment with recombinant human erythropoietin (rHuEPO) in patients with renal anaemia. However, the adequacy of dialysis is also significant. Many factors affect the process of dialysis and its effects. The purity of water used to make up the dialysate from concentrate is important. Inhibitors of erythropoiesis including ions and disinfectants may often be present in treated mains water. In addition, microbiological and pyrogenic contamination of the dialysate frequently occurs, sometimes leading to development or aggravation of anaemia in haemodialysis (HD) patients and also causing an immune response via cytokine activation. Inhibitors of erythropoiesis are also present in endogenous blood in patients with impaired renal function. Adequate dialysis is responsible for removing these mainly small, and possibly medium and large inhibitor molecules, thereby improving anaemia and enhancing response to rHuEPO. The biocompatibility and flux of the membrane used in HD may also have an effect. The removal of medium or large inhibitors of erythropoiesis is inefficient with cellulose membranes, but can potentially be achieved by using more permeable, high-flux membranes. However, in patients with adequate dialysis and sufficient iron and vitamin supplementation, the beneficial effects of a switch from standard cellulose to high-flux membranes have yet to be proven conclusively. Another area in which positive results on correction of anaemia have been seen in small studies is in the use of on-line haemodiafiltration, haemofiltration, or sterile dialysate. However, further large, controlled studies are needed to confirm these effects.

Dialysis: its role in optimizing recombinant erythropoietin treatment.

Although iron deficiency is probably the most important factor affecting response to recombinant erythropoietin (Epo, epoetin), other factors are of significance, including dialysis adequacy. Additionally, water treatment and distribution, sterilizants and the quality of the dialysate in terms of trace elements (particularly chloramine) are of importance in relation to erythropoiesis inhibition. Microbiological or pyrogenic contamination can cause or aggravate anaemia in haemodialysis patients, and the impact of enhanced production of cytokines should be taken into consideration. By removing small and (possibly) medium/large molecules, adequate dialysis is of paramount importance in correcting anaemia and optimizing epoetin therapy. The biocompatibility of dialysis membranes and flux are other important factors. As yet unknown uraemic toxins may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to hypothesize that, because anaemia improves after the start of dialysis with cellulose membranes, low molecular weight erythropoiesis inhibitors are involved, as well as medium/large molecular weight inhibitors, which are removed by more permeable membranes. However, in highly selected, adequately dialysed patients without iron or vitamin depletion, the effects of dialysis membrane type on haematological parameters and epoetin efficacy are smaller than might be expected from the results of uncontrolled studies. Improvement in anaemia has been observed using on-line haemofiltration, haemodiafiltration, and sterile dialysate. The results of prospective, randomized trials examining the impact of these factors on anaemia and the effectiveness of epoetin treatment are eagerly awaited.

Adequacy in pre‐dilution haemofiltration: Kt/V or infusion volume?

Kt/V is the main index of adequacy for diffusive and diffusive convective methods of extracorporeal depuration, yet there exists no universally acceptable validation of an adequacy index for the solely convective methods such as haemofiltration (HF). The aim of the present study is to analyse which of the parameters of adequacy used in two multicentre HF studies, Kt/V for urea or infusion volume, correlate best with nutritional parameters and can therefore be utilized for the evaluation of treatment dose in on-line pre-dilution HF. Twenty-three clinically stable patients were enrolled in the first study [3 months of haemodialysis (HD)+ 3 months of HF]. In the second study, 24 stable patients were studied in three phases: 6 months in HF, 6 months in HD and a further 6 months in HF; in this study, a target of Kt/V= 1.2 in all three periods was preestablished: 15 patients completed the full study. In both studies, we utilized the same monitor (AK 100/200 Ultra, Gambro), the same membrane (polyamide) and the same on-line prepared ultrapure dialysis fluid and sterile infusion solution. In both studies, we ensured that HF fulfilled the following parameters of adequacy: urea kinetics, cardiovascular and blood pressure stability (better in HF than in HD), common haematochemical and nutritional parameters, reduction in beta2-microglobulin levels, a good intra- and extra-session clinical outcome, and a good quality of life with morbidity and mortality rates no different from those of HD. HF proved to be an efficacious method of ensuring adequate depuration and a good quality of life for uraemic patients. We have shown that in longer periods of HF, a notable correlation between Kt/V and normalized protein catabolic rate (nPCR) and an equally good correlation between total ultrafiltration (UF)/dry weight ratio and nPCR could be achieved. In both studies, the patients showed a good level of epuration adequacy when total UF per session was at least 1.3 times the dry body weight. The total UF/body weight ratio thus seems to be an easy method in HF because of its greater ease of predictability and measurement, also when it is used independently of the Kt/V index.