There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage (in terms of treatment tolerance, nutritional parameters and pre-treatment beta-microglobulin levels) over a traditional membrane (Cuprophan). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan hemodialysis (Cu-HD), low-flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 +/- 10.46 mg/liter (23%) and in hemodiafiltration of 6.35 +/- 12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes (P = 0.032). The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications.

The primary aim of this multicenter, prospective, randomized cross-over study was to clarify whether a new model of hemodialysis (HD) potassium (K) removal using a decreasing intra-HD dialysate K concentration and a constant plasma-dialysate K gradient (treatment B) is capable of reducing the arrhythmogenic effect of standard HD, which has a constant dialysate K concentration and decreasing plasma-dialysate K gradient (treatment A). The secondary aim was to verify whether this new model is clinically safe. In treatment B, the initial dialysate K concentration had to be 1.5 mEq/liter less than the plasma K concentration, and exponentially decrease to 2.5 mEq/liter at the end of HD. Forty-two chronic HD patients with an increase in premature ventricular complexes (PVC) during dialysis were enrolled from 18 participating centers, and randomly assigned to either sequence 1 (ABA) or sequence 2 (BAB). A pool of 333 of 378 expected ECG Holter recordings were checked for signal quality; 269 (71%) from 36 patients (86%) had a satisfactory signal quality and 108 were selected for analysis (1 per patient per period). There was a difference in the natural logarithm of the increase in PVC/hr and PVC couplets/hr during HD between treatments A and B (1.70 +/- 1.59 vs. 1.09 +/- 1.76 and 0.94 +/- 0.86 vs. 0.64 +/- 1.01, a reduction of 36% and 32%, P = 0.011 and 0.047, respectively) without any carry over effect (P = 0.61 and 0.24, respectively). The fact that this decrease of one third is due to a lower plasma-dialysate K gradient is supported by the observation that it was more evident during the first than the last two hours of HD (a reduction in the natural logarithm of the increase in PVC/hr and PVC couplets/hr of 60% and 60%, P 0.002 and 0.009, vs. 26% and 17%, P = 0.098 and 0.332, respectively): the initial plasma-dialysate K gradient was 2.3 times lower during treatment B than during treatment A, without adversely affecting pre-HD plasma K levels. These results could have a considerably clinical impact not only because of the possibility of physiologically decreasing the arrhythmogenic effect of HD, but also because this effect can be considered a "marker" of the electrophysiological derangement induced by the administration of standard HD three times a week for years ("electric disequilibrium syndrome").

The OCM option of the haemodialysis machine provides a safe and accurate tool for continuous online monitoring of total urea clearance.

This approach suggests that changes in design of the dialyzer may affect its performance. The use of internal filtration is suggested to improve convection and dialyzer efficiency for larger solutes without the requirement for high volumes of replacement fluid, as is the case for current hemodiafiltration techniques.

Conductivity (CD)-based dialysance measurements precisely match urea dialysance with <5% difference. For measurement, a CD step-profile is applied by increasing dialysate inlet CD at time t0 for 10% above baseline and lasting for 2-5 min until t1, followed by a decrease to -4% until t2 and a final return to baseline, meanwhile recording dialysate CD at filter inlet (cdi) and outlet (cdo), dialysate flow (Qd), and ultrafiltration (UF)-rate (Qf). Electrolytic dialysance (KeCn) is calculated by KeCnI,J = (1 -[cdoI-cdoJ]/[cdiI-cdiJ])(Qd+Qf) with time index I not = J. The combinations in I,J are not equivalent: KeCn0,1 < KeCn1,2 < KeCn0,2. Each difference is 2% to 5%, and a difference versus urea clearance remains. An in vivo on-line clearance study (10 patients, 100 dialysis sessions, 265 measurements) with automatic electrolytical dialysance measurements and permanent data recording was conducted. Two methods were applied: a CD step-profile and a significantly smaller, dynamic CD bolus. Both were compared to laboratory reference of urea clearance. Reference Kt/V has been calculated using equilibrated single-pool methods and direct quantification. Urea generation was ignored. The results are as follows. The reference blood-side urea clearance was 164.0 +/- 11.8 ml/min, n = 265. The mean errors of the ionic dialysance results are KeCn0,1: -9.1 +/- 4.8%, n = 250; KeCn1,2: -5.6 +/- 4.4%, n = 250; KeCn0,2: 6.8 +/- 7.7%, n = 250; KeCnBolus: 0.1 +/- 4.8%, n = 162. The KeCnI,J error is urea distribution volume related. Kt/V comparison to equilibrated single pool is as follows: KeCn1,2t/V: 0.0 +/- 5.0% (r = 0.96, n = 45); KeCnBolust/V: 5.3 +/- 3.9% (r = 0.98, n = 44). The comparison to direct quantification is as follows: KeCn1,2t/V: -2 +/- 6.4% (r = 0.95, n = 68); KeCnBolust/V: 3.2 +/- 6.3% (r = 0.95, n = 66). V could roughly be measured. Dialysance measured by the step-function method was dependent on sodium load and distribution volume while the CD-bolus dialysance was not. Errors are generated by measurement-induced sodium shift that is sufficient even to estimate urea distribution volume. For dialysance measurements, small dynamic CD boli are preferable to stable step functions.