Abstract

Several studies have indicated that the improved elimination of middle molecules by convective renal replacement procedures might be associated with a better outcome in end-stage renal disease (ESRD). On-line mid-dilution hemodiafiltration (HDF) with the Nephros OLpur MD 190 hemodiafilter represents a novel extracorporeal renal replacement therapy concept to increase the removal of middle molecules. In a prospective cross-over study in 10 ESRD patients, this technique was compared to on-line post-dilution HDF with a conventional synthetic high-flux dialyzer, operated at its technical limit, concerning small and middle molecular solute removal. Each patient was treated 3 times for 4.0 +/- 0.4 hours with both filters. Blood flow was 400 mL/min, substitution flow (Q(S)) during mid-dilution HDF 200 mL/min, and during post-dilution HDF 100 mL/min, and effective dialysate flow of 700 - Q(S) mL/min. Instantaneous clearances, reduction ratios (RR), and middle molecule mass transfer in continuously collected dialysate were determined. While urea and creatinine clearances were significantly lower (6.4% and 3.9%, respectively), middle molecule removal was much more efficient in mid-dilution HDF over the whole range of investigated proteins: compared to post-dilution HDF, beta(2)-microglobulin (11.8 kD) clearance (165.8 +/- 26.59 vs. 201.9 +/- 20.63 mL/min; P < 0.001), RR (80.0 +/- 5.4% vs. 82.2 +/- 5.7%; P < 0.001), and dialysate mass transfer (53% higher; P < 0.001) were significantly higher. For the larger middle molecules, cystatin C (13.4 kD) and retinol-binding protein (21.2 kD), mid-dilution HDF resulted in an even more superior performance, indicated by significantly higher values of all investigated parameters. On-line mid-dilution HDF with the Nephros OLpur MD 190 hemodiafilter appears to be a true technologic step ahead in terms of improved middle molecule removal. This efficient procedure gives hope to play a role in preventing or at least retarding dialysis-related long-term complications, such as beta(2)m amyloidosis, in ESRD patients, and may contribute to a more adequate dialysis therapy.

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