**3.1 Pulse push/pull HD**

Repetitive procedures of ultrafiltration and backfiltration during PPPHD are achieved by replacing conventional roller pumps with pulsatile pumps for both blood and dialysate. During an early trial, a T-PLS pump (Twin Pulse Life Supporter, AnC Bio Inc., Seoul, Korea) was used as pulsatile pumps for blood and dialysate (K. Lee et al., 2008). The T-PLS consists of blood and dialysate sacs, a reciprocating actuator, and a motor-cam assembly (J. J. Lee et al., 2005). The actuator is located between blood and dialysate sacs (Fig. 5). When the actuator squeezes the blood sac, blood in the sac can move only in the forward direction due to the presence of one-way check valves. At the same time, the dialysate sac expands and is filled with fresh dialysate. In the same manner, dialysate also moves forward when the sac is squeezed, and these reciprocating movements create pulsatile flow. By setting their phase difference at 180O degrees, the respective pushing phases of blood and dialysate pumps alternate, and TMPs cycle between positive and negative, which drive consecutive periods of ultrafiltration and backfiltration.

<sup>1</sup> Continuous Renal Replacement Therapy

### Fig. 5. T-PLS pump for the original PPPHD

126 Progress in Hemodialysis – From Emergent Biotechnology to Clinical Practice

maximal levels and the total filtration volumes achieved are far greater than that of any other treatment modality. In addition to the filtration quantity, repetitive cycles in a shorter time than the time required for a protein layer to be established ensure superior membrane use throughout treatment, which further inhibits albumin loss. However, given the advances represented by membranes with high β2M sieving coefficients (>0.8), but very small albumin sieving coefficients (<0.01) (Ronco et al., 2002), the differences between push/pull HDF and high-flux HD with respect to β2M removal may be reduced, and albumin leakage less problematic. To an extent in modern dialysis practice, albumin permeable membranes are even considered to remove non-soluble and/or much larger molecules (De Smet et al., 2007, Samtleben et al., 2003). Therefore, a prolonged prospective study on push/pull HDF may be worthwhile to determine the benefits of this modality

Flow patterns, that is, pulsatile versus non-pulsatile, remain topics of research for treatments requiring extracorporeal blood circulation. Despite controversy, blood pulsation has been accepted to have a benefit during cardiopulmonary bypass, because it achieves greater perfusion to peripheral vessels and end-organs (Dapper et al., 1992, Orime et al., 1999). Furthermore, blood pulsation in a pediatric CRRT1 animal model was found to deliver adequate performance over a 2-hour period in terms of ultrafiltration rates and cross-filter blood pressure drops (Lopez-Herce et al., 2006, Ruperez et al., 2003). In addition, it was also found that the pulsatile flow tends to enhance ultrafiltration rates versus non-pulsatile flow (Lim et al., 2009, Runge et al., 1993), which attributed to an increased rheological power of pulsatile flow. However, little clinical or experimental evidence is available that explains the efficacy of pulsatile flow during dialysis. Pulse push/pull HD is a convection enhanced dialysis treatment, based on the use of pulsatile flows to achieve a cyclic repetition of forward and backward filtration. As explained in the previous section, the repetitive manner of ultrafiltration and backfiltration contributes substantially to total volume exchange and

Repetitive procedures of ultrafiltration and backfiltration during PPPHD are achieved by replacing conventional roller pumps with pulsatile pumps for both blood and dialysate. During an early trial, a T-PLS pump (Twin Pulse Life Supporter, AnC Bio Inc., Seoul, Korea) was used as pulsatile pumps for blood and dialysate (K. Lee et al., 2008). The T-PLS consists of blood and dialysate sacs, a reciprocating actuator, and a motor-cam assembly (J. J. Lee et al., 2005). The actuator is located between blood and dialysate sacs (Fig. 5). When the actuator squeezes the blood sac, blood in the sac can move only in the forward direction due to the presence of one-way check valves. At the same time, the dialysate sac expands and is filled with fresh dialysate. In the same manner, dialysate also moves forward when the sac is squeezed, and these reciprocating movements create pulsatile flow. By setting their phase difference at 180O degrees, the respective pushing phases of blood and dialysate pumps alternate, and TMPs cycle between positive and negative, which drive consecutive periods

versus other forms of convective renal replacement.

**3. Pulse Push/Pull Hemodialysis (PPPHD)** 

convective mass transfer.

**3.1 Pulse push/pull HD** 

of ultrafiltration and backfiltration.

1 Continuous Renal Replacement Therapy

The hemodialytic efficiencies of PPPHD have been demonstrated *in vitro* and also *in vivo*, and these studies have shown that PPPHD substantially improves the clearances of uremic marker molecules, particularly for mid-sized molecules (Table 1) (K. Lee et al., 2008), which is believed to be due to a higher level of total filtration. Pressure profiles also showed obvious oscillations of TMPs throughout treatment, and their magnitudes were significantly larger than those observed in conventional hemodialysis (CHD) mode.


Table 1. Solutes Clearances. (CHD, conventional high-flux HD; PPPHD, pulse push/pull HD; BPM, beats per minute; QB, blood flowrate; QD, dialysate flowrate; BUN, blood urea nitrogen; NS, not significant)

Increased filtration volumes in the PPPHD unit may also be due to reduced membrane fouling. In an *in vivo* setup on PPPHD, one cycle of ultrafiltration and backfiltration took 3 seconds at a pulse frequency of 20 bpm (K. Lee et al., 2008). When ultrafiltration and backfiltration times were defined as the durations of positive and negative TMPs, respectively, ultrafiltration and backfiltration times for the PPPHD unit were 1.68±0.02 and 1.31±0.03 seconds, respectively. Since protein concentration polarization on the blood-side membrane develops during the forward filtration phase and it is reduced by backfiltration, membrane convective capacity might be better maintained during PPPHD than during CHD, showing smaller reductions in post-dialysis hydraulic permeabilities (K. Lee et al., 2008). Furthermore, PPPHD-treated animals were tolerably sustained and their physiologic parameters were stable.

Pulse Push/Pull Hemodialysis: Convective Renal Replacement Therapy 129

Fig. 6. Dual Pulse Pump (DPP). Its body is made of an aluminum alloy, and comprises a base plate, a unidirectional electric motor (not seen), a cam, and four actuators. It can also contain two separate silicone tubes. Pulsatile flow is generated by squeezing each dialysate and effluent tubing segments. (A1~A4, actuators 1 to 4; p1~p6, silicone tubing segments at

Fig. 7. Tube Openness Diagram for Dialysate (upper) and Effluent Pump (below) of DPP.

openness increases whereas p1 tube openness decreases. During the 2nd phase (θ=90°~180°), with p1 closed, p2 begins to be squeezed and simultaneously p3 begins to open, and pure dialysate is driven into the hemodialyzer. Closure of p1 fulfills the same function as atrioventricular valve closure during left ventricular systole, which prevents retrograde flow. During the 3rd phase (θ=180°~270°), p3 is closed, while p1 and p2 remain

positions 1 to 6, respectively)

Pulse push/pull HD is conceptually similar to push/pull HDF. Both modalities were devised to increase total filtration level by alternating forward and backward filtration. However, the underlying design of PPPHD differs from push/pull HDF, and thus, the supplementary component required to switch from ultrafiltration to backfiltration phases or vice versa used in push/pull HDF was eliminated for PPPHD and the entire system was remarkably simplified.
