In vivo Removal of High- and Low-Molecular-Weight Compounds in Hemodiafiltration with On-Line Regeneration of Ultrafiltrate

Abstract

Background: Current methods of renal replacement therapy, combining convection and diffusion, are largely unsatisfactory in removing uremic toxins. Adsorption is a third mechanism that has been applied in extracorporeal therapy. This study evaluates the impact of hemodiafiltration with on-line regeneration of ultrafiltrate, a new two-step integrated sorbent system, on in vivo removal of a wide spectrum of solutes with different molecular weights. Methods: Pre- and post-dialysis concentrations of small, medium-size, and large molecules were determined in ten patients undergoing regular hemodiafiltration treatments with on-line regeneration of the ultrafiltrate. We also analyzed, at different times of the same dialysis session, the inlet and outlet ultrafiltrate; the latter had been regenerated by the sorbent cartridge and was used as reinfusion liquid. The mean dialysis time was 260 ± 21.2 min with a blood flow of 361 ± 33.3 ml/min and a reinjection volume of 3.6 ± 0.2 l/h. Results: Urea, creatinine and phosphate reduction ratio were respectively 69.8 ± 8.2, 61.9 ± 5.5, and 40.2 ± 17.3%. Removal of medium-size markers such as calcitonin, osteocalcin, β₂-microglobulin, cystatin C, myoglobin and prolactin varied between 24 and 60%. The percentage of reduction for retinol binding protein and α₁-microglobulin was negligible and we were unable to demonstrate any removal of α₁-acid glycoprotein, pre-albumin, and albumin in the regenerated ultrafiltrate. Conclusion: The hemodiafiltration with on-line regeneration of ultrafiltrate is a new hemodialysis system, which allows uremic toxin removal over a wide molecular-weight spectrum.

Effect of Different Dialysis Modalities on Microinflammatory Status and Endothelial Damage

“…It is generally accepted that hemodiafiltration offers a highly effective dialysis modality that widens the spectrum of uremic toxins removed from small to medium-sized molecular solutes (18 -20). On-line hemodiafiltration using high-substitution fluid produces a greater clearance of large uramic toxins (21,22). Furthermore, we have reported that dialysis modalities with high convective transport are capable of reducing but not normalizing the percentage of CD14 ϩ CD16 ϩ monocytes (13).…”

Relationship of Serum Cystatin C with C-Reactive Protein and Apolipoprotein A1 in Patients on Hemodialysis

“…Although there is limited evidence about the range of cystatin C concentration during hemodialysis therapy, the levels before dialysis are in agreement with those measured by other authors and significantly higher post-dialysis than pre-dialysis. [17,20] This increase can be attributed to the low-flux membranes used, which retain cystatin C and other middle molecular weight molecules, in contrast to high-flux hemodialyzers or hemodiafiltration, which allow the removal of the above compounds and result in a substantial decrease in the post-dialysis levels of cystatin C. [21,22] We intended to determine if the increased concentration of serum cystatin C in hemodialysis patients is connected to the inflammatory factor CRP as well as to markers of atherosclerosis. As has been previously reported, the inflammatory process is related to atherosclerosis in chronic kidney disease [23,24] and is revealed by a release of CRP and inflammatory cytokines (i.e., Il-6) secreted by inflammatory cells present in atherosclerotic lesions [14,25] and also by leukocytes in contact with dialysis membranes.…”

Normal and Pathologic Concentrations of Uremic Toxins

“…22,31 The highest mass concentration was detected for the acute phase macromolecule a1-acid glycoprotein. 54 Most frequently reported concentrations concerned b2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone (PTH). There were large variations in binding of protein-bound solutes.…”