Thoughts and Progress Pulse Push/Pull Hemodialysis: In Vitro Study on New Dialysis Modality With Higher Convective Efficiency *†‡Kyungsoo Lee, *†‡Sa Ram Lee, *†‡Cho Hae Mun, and †‡§¶Byoung Goo Min *Interdisciplinary Program in Biomedical Engineering Major, Seoul National University; †Korea Artificial Organ Center; ‡Cancer Research Institute, Seoul National University Hospital; §Department of Biomedical Engineering, College of Medicine, Seoul National University; and ¶Institute of Medical Engineering, Medical Research Center, Seoul National University, Seoul, Korea Abstract: Midsize molecule retention is related with renal-failure-associated mortality. Here, the authors describe a new dialysis modality, pulse push/pull hemodi- alysis (PPPHD), which increases convective clearance. Blood and dialysate are circulated by a pulsatile pump, but with pulsatile flow patterns that are 180° out of phase.This causes blood-to-dialysate pressure gradients that oscillate between positive and negative, and which cause consecu- tive periods of ultrafiltration and backfiltration. The devised PPPHD was compared with conventional high- flux hemodialysis (CHFHD) in terms of solute clearances, albumin loss, and total protein levels. Human plasma con- taining dissolved uremic marker molecules was used as a blood substitute, and clearances were investigated for blood urea nitrogen, creatinine, vitamin B12, and inulin. Observed clearances were found to be significantly higher for PPPHD by approximately 3–14% for low-molecular- weight solutes, by 47–48% for vitamin B12, and by 38–49% for inulin than for CHFHD. No albumin loss was observed in either of these two study groups. The authors conclude that PPPHD offers a simple straightforward means of enhancing uremic molecule removal by in- creasing total ultrafiltration volume without the need to infuse replacement fluid. Key Words: Pulsatile flow— Hemodialysis—Convection—Clearance—Ultrafiltration— Backfiltration—Transmembrane pressure. Maintenance renal replacement therapies have been continuously improved over the past decades and technical innovations continue to enhance patient outcomes. These include improvements in midsize solute clearances, as the retention of these species is related to renal-failure-associated mortal- ity (1). Hemodiafiltration (HDF) and high-flux hemodialysis are both used to increase convective clearance for chronic renal failure patients. Both modalities make use of a synthetic membrane with high water permeability and sieving capacities. HDF can usually achieve better convective clearance than high-flux hemodialysis by increasing total ultrafiltra- tion volume (2), but requires a large amount of substitution fluid infusion, which complicates the system. Thus, various strategies have been devised to enhance convective mass transfer without the need for sterile replacement infusion. In one such system, ultrafiltrate extracted from a hemofilter is regenerated and then reinfused into the blood- stream, which is sequentially dialyzed (3). Ultra- filtrate regeneration in paired filtration–dialysis systems eliminates the requirement for exogenous substitution infusion. Dual-stage HDF using dia- lyzers in series also enhances the total amount of ultrafiltration, but no replacement fluid infusion is required because continuous filtration at the upstream dialyzer, which exceeds the desired weight loss, is compensated for by backfiltration at the downstream dialyzer (4–6). These two modalities provide significantly greater convective clearance, but they require two filters which make these systems complex and raise treatment costs. A similar but simpler method, the so-called push/pull HDF method, was introduced to increase convective mass transfer. This system relies on repeated cycles of ultrafiltration and backfiltration during hemodialysis (7–11). Such pressure-controlled push/pull HDF systems can maintain transmembrane pressures (TMPs) at the maximum permissible level through- out treatment (12), but require an additional device, that is, a double-compartment piston pump, to regu- late instantaneous blood and dialysate pressures (13). Volumetrically controlled high-flux hemodialy- sis also adequately clears midsize solutes without sterile fluid infusion, but the internal filtration involved leads to limited middle-size molecular removal versus HDF or hemofiltration, due to limi- tations imposed by the greater pressure gradients. doi:10.1111/j.1525-1594.2008.00561.x Received May 2007; revised July 2007. Address correspondence and reprint requests to Dr. Byoung Goo Min, Department of Biomedical Engineering, College of Medicine, Seoul National University, 28 Yungun-dong, Chongno- gu, Seoul, 110-744, Korea. E-mail: bgmin@plaza.snu.ac.kr Artificial Organs 32(5):406–419, Blackwell Publishing, Inc. © 2008, Copyright the Authors Journal compilation © 2008, International Center for Artificial Organs and Transplantation and Blackwell Publishing 406