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Abstract: FR-PO790

The Effect of Isohydric Hemodialysis on Uremic Retention Solutes

Session Information

Category: Dialysis

  • 601 Standard Hemodialysis for ESRD

Authors

  • Lowenstein, Jerome, New York University Medical Center, New York, New York, United States
  • Etinger, Aleksey, New York University School of Medicine , New York, New York, United States
  • Kumar, Sumit Raman, Yale New Haven Hospital, New Haven, Connecticut, United States
  • Ackley, William, Yale New Haven Hospital, New Haven, Connecticut, United States
  • Soiefer, Leland Russell, New York University School of Medicine , New York, New York, United States
  • Grossman, Eric B., New York University Medical Center, New York, New York, United States
  • Matalon, Albert, New York University Medical Center, New York, New York, United States
  • Holzman, Robert, NYU School of Medicine, New York, New York, United States
  • Meijers, Bjorn, University Hospitals Leuven, Leuven, Belgium
Background

There is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate (IS), p-cresyl sulfate (PCS) and kynurenic acid (KA), play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable.
We had previously observed that the concentration of free solute and its unbound fraction were markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and the changes attributable to the higher serum pH at the end of hemodialysis. In vitro, acidification of uremic plasma to pH 6 greatly increased the proportion of unbound indoxyl sulfate.

Methods

We tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mEq/L for the initial half of hemodialysis (“isohydric dialysis”). Eight stable hemodialysis patients underwent “isohydric dialysis” and, midway, were switched to standard buffer (37 mEq/L). A second dialysis, 2 days later, employed standard buffer throughout.

Results

We found a clearcut separation of blood pH and bicarbonate concentrations 90 minutes following “isohydric dialysis” (pH = 7.37, HCO3 =22.4 mEq/l) and standard dialysis (pH= 7.49, HCO3 = 29.5). Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis .

Conclusion

These findings suggest that modification of dialysis technique that would expose blood to a transient decrease in pH might increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of protein-bound uremic retention solutes.

Funding

  • Private Foundation Support