Kyungsoo Lee

Cell-based approaches for the treatment of systemic inflammation

Acute and chronic solid organ failures are costly disease processes with high mortality rates. Inflammation plays a central role in both acute and chronic organ failure, including heart, lung and kidney. In this regard, new therapies for these disorders have focused on inhibiting the mediators of inflammation, including cytokines and free radicals, with little or no success in clinical studies. Recent novel treatment strategies have been directed to cell-based rather than mediator-based approaches, designed to immunomodulate the deleterious effects of inflammation on organ function. One approach, cell therapy, replaces cells that were damaged in the acute or chronic disease process with stem/progenitor technology, to rebalance excessive inflammatory states. As an example of this approach, the use of an immunomodulatory role of renal epithelial progenitor cells to treat acute renal failure (ARF) and multiorgan failure arising from acute kidney injury is reviewed. A second therapeutic pathway, cell processing, does not incorporate stem/progenitor cells in the device, but rather biomimetic materials that remove and modulate the primary cellular components, which promote the worsening organ tissue injury associated with inflammation. The use of an immunomodulating leukocyte selective cytopheretic inhibitory device is also reviewed as an example of this cell processing approach. Both of these unconventional strategies have shown early clinical efficacy in pilot clinical trials and may transform the therapeutic approach to organ failure disorders.

Mathematical analysis for internal filtration of convection-enhanced high-flux hemodialyzer

Structural modifications using a conventional hemodialyzer improved the internal filtration and clearance of middle molecular weight wastes by enhanced convection effect. In this study, we employed a mathematical model describing the internal filtration rate as well as the hemodynamic and hematologic parameters in highflux dialyzer to interpret the previous reported experimental results. Conventional high-flux hemodialysis and convection-enhanced high-flux hemodialysis were configured in the mathematical forms and integrated into the iterative numerical method to predict the internal filtration phenomena inside the dialyzers during dialysis. The distributions of blood pressure, dialysate pressure, oncotic pressure, blood flow rates, dialysate flow rates, local ultrafiltration, hematocrit, protein concentration and blood viscosity along the axial length of dialyzer were calculated in order to estimate the internal filtration volume. The results show that the filtration volumes by internal filtration is two times higher in a convection-enhanced high-flux hemodialyzer than in a conventional high-flux hemodialzer and explains the experimental result of improved clearance of middle molecular size waste in convection-enhanced high-flux hemodialyzer.

Substitution-free hemodiafiltration.

Hemodiafiltration (HDF) has been reported to deliver better dialysis outcomes in patients with end-stage renal disease. Technical advances now allow online-based HDF to be used on a clinical basis. However, HDF is being performed at a limited rate because of the requirement of exogenous fluid infusion, which causes safety and cost issues. Therefore, various modifications on HDF strategies have been devised to achieve the HDF without exogenous fluid infusion, which can be achieved by spontaneous fluid reinfusion. In this article, substitution-free HDF strategies are reviewed in detail, with specific attention to technical aspects of the methodology, in vivo and in vitro efficacies, and applicability to clinical use.

Engineering perspective on the evolution of push/pull-based dialysis treatments.

The incidence of kidney disease is rapidly increasing worldwide, and techniques and devices for treating end-stage renal disease (ESRD) patients have been evolving. Better outcomes achieved by convective treatment have encouraged the use of synthetic membranes with high water permeability in clinical setups, and high-flux hemodialysis (HD) and hemodiafiltration (HDF) are now preferred forms of convective therapy in ESRD patients. Push/pull-based dialysis strategies have also been examined to increase convective mass transfer in ESRD patients. The push/pull technique uses the entire membrane as a forward filtration domain for a period of time. However, backfiltration must accompany the forward filtration to compensate for the fluid depletion resulting from the forward filtration, making it necessary to switch the membranes to a backfiltration domain. This paper attempts to describe the advancement of push/pull-based renal supportive treatments in terms of their technical description, hemodialytic efficacy including fluid management accuracy and applicability for clinical use. How the optimization of push and pull actions could translate into better convective efficiency will also be discussed in depth.