Uric acid distribution volume calculated by kinetic modeling and extracellular volume predicted by bioimpedance method.

BACKGROUND: Several reports indicate that extracellular volume predicted by bioimpedance analysis method is associated with hydration status of hemodialysis patients. THEORY: Fundamentally, uric acid does not cross cell membranes by simple diffusion, either by facilitated diffusion or by active transport. In addition, uric acid cannot move through cell membranes in most tissues other than those involved in uric acid excretion. These facts support the interpretation that uric acid distribution volume would therefore correlate with extracellular volume. METHODS: We examined correlation between uric acid distribution volume calculated by uric acid mass-balance modeling from regular blood test results and extracellular volume predicted by bioimpedance analysis predicted by BCM (Fresenius Medical Care) in 53 patients. RESULTS: There was a significant correlation between uric acid distribution volume (x) and extracellular volume predicted by bioimpedance analysis (y): y = 0.69x + 3.39, r2 = 0.61, p < 0.0001. Bland-Altman analysis showed systematic error for uric acid distribution volume versus extracellular volume predicted by bioimpedance analysis (mean difference between uric acid distribution volume and extracellular volume predicted by bioimpedance analysis was 0.94 L, 95% confidence interval of difference was -3.29 to 5.17 L). CONCLUSION: Uric acid distribution volume calculated by uric acid mass-balance modeling from regular blood test results may be an alternative marker of extracellular volume predicted by bioimpedance analysis.

Push/pull hemodiafiltration.

Push/pull hemodiafiltration is characterized by alternate filtration and backfiltration, while sterile pyrogen-free dialysate is flowing through a hemodiafilter. During the filtration phase, uremic substances are eliminated not only by diffusive, but also by convective transport. During the backfiltration phase, dialysate is quickly pushed to the blood side (i.e. backfiltration) so as to make up for the excessive reduction in body fluid that has developed during the immediately preceding filtration phase. In the most recently improved version of push/pull hemodiafiltration, the body fluid replacement volume is over 120 liters during a 4- hour treatment. This replacement of a large amount of body fluid may be due to the increased filtration rate in the hemodiafilter resulting from failure of the complete formation of a protein gel layer on the blood side surface. The filtration time in push/pull hemodiafiltration is so short that the also short backfiltration to follow may take over before the protein gel layer is completely formed on the membrane surface. Since the filtration and backfiltration times are much shorter in push/pull hemodiafiltration than the time for blood to pass through the hemodiafilter, it is concentrated and diluted many times (approx. 25 times) before it leaves the hemodiafilter. Therefore, push/pull hemodiafiltration is functionally similar to a predilution hemodiafiltration. The reduction rate of beta-microglobulin was greater by push/pull hemodiafiltration than by hemodialysis, when a high-flux polysulfone hemodiafilter was employed. However, the difference in the reduction rate was rather small between them, because of the improved hemodiafilters, which remove so much beta2-microglobulin only by dialysis. Nevertheless, restless legs syndrome, irritability, insomnia and pruritus were alleviated after switching the treatment modality from hemodialysis to push/pull hemodiafiltration. This may indicate that these symptoms are caused by the accumulation of uremic substances larger than beta2-microglobulin.

Which Kt/V is the most valid for assessment of both long mild and short intensive hemodialyses?

It is unclear at present which mathematical modeling Kt/V(urea) is valid for assessment of both long mild hemodialysis (HD) and short intensive HD, the single-pool modeling Kt/V (Kt/Vsp) based on the pre- and postdialysis serum urea concentrations, double-pool modeling Kt/V (Kt/Vdp) based on the predialysis concentration and the estimated postdialysis equilibrated concentration, or Kt/V calculated on the basis of dialyzer urea clearance, HD session duration and urea distribution volume (Kt/Vdl). Thus, the respective Kt/V during a short intensive HD was compared with its counterpart Kt/V during a long mild HD, where the same amount of urea is removed during both HD treatments. It was found that the Kt/Vsp and Kt/Vdl during short intensive HD were significantly greater than the respective Kt/V during the long mild HD. On the other hand, there was no significant difference in the Kt/Vdp between the long mild and short intensive HDs. In conclusion, Kt/Vdp may be more valid for assessment of both long mild and short intensive HDs.

Platelet GPIIb/IIIa is activated and platelet-leukocyte coaggregates formed in vivo during hemodialysis.

BACKGROUND/AIM: During hemodialysis, platelets and leukocytes are activated and form platelet-leukocyte coaggregates in which GPIIb/IIIa (CD41/CD61) and CD62P (P-selectin) are involved. However, it is still controversial whether platelet activation and platelet-leukocyte coaggregate formation are dependent on the dialyzer membrane material. METHOD: We examined the appearance of activation-dependent antibody on platelets as an index of platelet activation, and the appearance of platelet-specific antigen on leukocytes as an index of platelet-leukocyte coaggregation, during hemodialysis in 7 patients treated using regenerated cellulose (RC) membrane and next using polysulfone (PS) membrane. In order to reduce the influence of factors other than dialyzer membrane material, this study was conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate. Moreover, flow cytometric techniques with whole blood were employed, which reduce artificial cell activation during the cell or plasma separation procedure. The platelet-specific monoclonal antibodies used in this study were anti-CD61, PAC-1 (which recognizes only the conformationally activated GPIIb/IIIa) and anti-CD62P. RESULTS: Changes in the percentage of PAC-1-positive platelets were significantly greater during hemodialysis with RC than with PS. However, changes in the percentage of CD62P-positive platelets were not significantly different between hemodialysis with RC and PS. Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS. Although changes in percentage of PAC-1-positive platelets did not parallel those of CD62P-positive platelets during hemodialysis, there was a significant positive correlation between the percentage of CD61-positive leukocytes and the percentage of CD62P-positive leukocytes. CONCLUSION: This study, conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate in order to reduce the influence of factors other than the dialyzer membrane material, demonstrated that both the degrees of GPIIb/IIIa activation and platelet-leukocyte coaggregation were greater during hemodialysis with RC than PS.

Changes in Mac-1 and CD14 expression on monocytes and serum soluble CD14 level during push/pull hemodiafiltration.

BACKGROUND/AIM: Employment of treated dialysate as replacement fluid raises concerns about exposure of patients to pyrogenic substances. This study was undertaken to evaluate the safety of treated dialysate as the replacement fluid for push/pull hemodiafiltration. METHODS: In the present study, changes in the expressions of Mac-1 and CD14 on monocytes, which are upregulated by monocyte activation, were analyzed by flow cytometry, and the serum level of sCD14 which elevates by monocyte activation was measured by enzyme-linked immunosorbent assay (ELISA) during treatment in 7 patients on hemodialysis with regenerated cellulose (RC) membrane, polysulfone (PS) membranes and by push/pull hemodiafiltration (HDF) with PS membranes in a cross-over fashion. RESULTS: During hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration with PS, both Mac-1 and CD14 expressions on monocytes significantly increased by passing through the artificial kidneys, and, accordingly, the respective values downstream of the artificial kidneys were significantly higher than the predialysis values, even when the lipopolysaccharide level in dialysate was not detectable by Limulus assay. There was no significant variation in serum sCD14 levels during any of the hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration. However, during hemodialysis with PS or push/pull hemodiafiltration with PS, changes in Mac-1 and CD14 expression on monocytes were significantly smaller than those during hemodialysis with RC. CONCLUSION: Monocytes are activated to a greater extent during hemodialysis with RC membranes than during push/pull HDF with PS membranes. We consider that push/pull HDF may be safer than hemodialysis with RC membrane and that it is as safe as hemodialysis with the PS membrane in terms of monocyte activation, when pyrogen-free dialysate is employed.