Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy.

BACKGROUND: The Genius single-pass batch system for hemodialysis contains a closed reservoir and dialysate circuit of 75 L dialysate. The unused dialysate is withdrawn at the top of the reservoir and the spent fluid is reintroduced into the container at the bottom. Although it has been claimed that both fractions remain unmixed during the dialysis session, no direct proof of this assumption has yet been provided. In the present study, we investigated whether contamination of the unused dialysate with uremic solutes occurred and at which time point it began. Two different dialysate temperatures were compared. METHODS: Ten chronic hemodialysis patients were dialyzed twice with the Genius system, with dialysate prepared at 37 degrees C and 38.5 degrees C, respectively. The sessions lasted 270 minutes with blood/dialysate flow set at 300 mL/min. Dialysate was sampled at 5, 60, 180, 210, 225, 230, 235, 240, 255, and 270 minutes both from the inlet and outlet dialysate line and blood was sampled from the arterial line predialysis, after 4 hours, and postdialysis. All samples were tested for osmolality, urea, creatinine, p-cresol, hippuric acid, and indoxyl sulfate. RESULTS: Uremic solutes appeared in the inlet dialysate line between 3 hours 50 minutes and 4 hours 10 minutes after the start of dialysis, corresponding to 68.6 and 74.7 L spent dialysate, respectively (37 degrees C vs. 38.5 degrees C; P = NS). No difference in the amount of removed solutes and in the serum levels was observed between 37 degrees C and 38.5 degrees C. A Kt/V of 1.17 +/- 0.20 and 1.18 +/- 0.26, respectively, was reached with the 37 degrees C and 38.5 degrees C dialysate temperature (P = NS). CONCLUSION: Contamination with uremic solutes occurred at the dialysate inlet only near the end of the session when small quantities of fresh dialysate were left in the container. Differences in dialysate temperature did not result in a different separation between used and unused dialysate, or in differences in removal of toxins or Kt/V.

Back to the future: middle molecules, high flux membranes, and optimal dialysis.

Middle molecules can be defined as compounds with a molecular weight (MW) above 500 Da. An even broader definition includes those molecules that do not cross the membranes of standard low-flux dialyzers, not only because of molecular weight, but also because of protein binding and/or multicompartmental behavior. Recently, several of these middle molecules have been linked to the increased tendency of uremic patients to develop inflammation, malnutrition, and atheromatosis. Other toxic actions can also be attributed to the middle molecules. In the present publication we will consider whether improved removal of middle molecules by large pore membranes has an impact on clinical conditions related to the uremic syndrome. The clinical benefits of large pore membranes are reduction of uremia-related amyloidosis; maintenance of residual renal function; and reduction of inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded that middle molecules play a role in uremic toxicity and especially in the processes related to inflammation, atherogenesis, and malnutrition. Their removal seems to be related to a better outcome, although better biocompatibility of membranes might be a confounding factor.

Uremic toxins: removal with different therapies.

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.