Eungtaek Kang

Advanced glycation end products induce apoptosis and procoagulant activity in cultured human umbilical vein endothelial cells

Hyperglycemia and the late products of non-enzymatic glycosylation, called advanced glycation end products (AGEs), play an important role in the development of microvascular complications in diabetes mellitus. Previous studies have reported that a high glucose environment triggered apoptotic changes in human umbilical vein endothelial cells (HUVECs). Therefore, we investigated whether AGEs contribute to the development of apoptosis and prothrombotic activity in HUVECs. After incubation of HUVECs with 0.2, 2.2, 22, 220 and 2200 nM of AGE-bovine serum albumin (BSA) from 6 to 48 h, we assayed the degree of apoptosis and procoagulant activity (PCA). There were no significant differences between HUVECs cultured for 48 h with 0.2, 2.2 or 22 nM of AGE-BSA and in controls in the proportion of apoptotic cells (3.5 +/- 0.8%, 3.9 +/- 1.5% and 5.2 +/- 1.1% vs. 2.5 +/- 0.6%). However, the proportion of apoptotic cells increased significantly to 36.7 +/- 9.8% in 220 nM of AGE-BSA, and 72.3 +/- 10.2% in 2200 nM of AGE-BSA (P < 0.001). PCA levels were 142 +/- 10 s after 6 h of exposure to 22 nM (P < 0.01), 131 +/- 5 s after 6 h of exposure to 220 nM (P < 0.001), and 106 +/- 4 s after 6 h of exposure to 2200 nM of AGE-BSA (P < 0.001). These values show that PCA was shortened significantly from the basal value of 161 +/- 6 s, and remained below the basal level until the end of the study. The amount of tissue factor was also significantly increased in 22 and 220 nM of AGE-BSA compared to the controls. In conclusion, this study showed that AGEs could induce apoptosis and increase procoagulant activity in cultured HUVECs. We suggest that AGEs can contribute to the development of microvascular complications through cell death of HUVECs and functional changes of the blood vessels.

A wearable artificial kidney: technical requirements and potential solutions

Recently, new approaches for miniaturization and transportability of medical devices have been developed, paving the way for wearability and the possibility of implantation, for renal replacement therapies. A wearable artificial kidney (WAK) is a medical device that supports renal function during ambulation or social activities out of hospital. With the aim of improving dialysis patients’ quality of life, WAK systems have been developed for several decades. However, at present there are a lot of technical issues confronting the attempt to apply WAK systems in clinical practice. This article focuses on technical requirements and potential solutions for WAKs and reviews up-to-date approaches related to dialysis membrane, dialysate regeneration, vascular access, patient-monitoring systems and power sources for WAKs.

Enhancement of solute removal in a hollow-fiber hemodialyzer by mechanical vibration.

Better solute clearance, particularly of middle-molecular-weight solutes, has been associated with improved patient outcomes. However, blood-membrane interaction during dialysis results in the development of secondary mass transfer resistances on the dialyzer membrane surface. We discuss the potential effects of mechanical vibration on the diffusion, convection and adsorption of uremic solutes during dialysis. For sinusoidal and triangular vibratory motions, we conceptualized the hemodynamic changes inside the membrane and consequent effects on membrane morphology. Longitudinal vibration generates reverse flow by relative membrane motion, and transverse vibration generates a symmetric swirling flow inside the hollow fiber, which enhances wall shear stress and flow mixing. Moreover, the impulse induced by triangle wave vibration could provide higher absorption capacity to middle-molecular-weight solutes. Mechanical vibration could enhance solute removal by minimizing membrane morphology changes resulting from blood-membrane interaction during hemodialysis. These effects of mechanical vibration can be helpful in extracorporeal blood purification therapies including continuous, portable and wearable systems.

Effect of fiber structure on dialysate flow profile and hollow-fiber hemodialyzer reliability: CT perfusion study.

Background Uniform dialysate distributions in hollow-fiber hemodialyzers facilitate effective solute removal, and the fiber structure inside hemodialyzers plays a significant role in determining dialysate flow distribution and dialysis efficiency. The authors analyzed the effects of undulated fibers on dialysate flow profiles and hemodialyzer reliability using a perfusion CT technique. Method Using a multi-detector row CT unit, perfusion studies were performed on two different types of hemodialyzers: (A) straight fiber configuration; (B) undulated fiber configuration (wavy-shaped fibers). Deconvolution theory was used for image processing to derive dialysate flows, dialysate volumes, and mean transit time distributions. Three-dimensional perfusion maps for the two types of hemodialyzers were reconstructed using high resolution images and these parameters were compared at hemodialyzer midsections. Results Dialysate maldistributions were observed in both types of hemodialyzer. However, dialysate flow distributions were more uniform in the undulated-fiber hemodialyzer, whereas more complex flow distributions developed in straight-fiber hemodialyzer. Reliability as determined using intraclass correlation coefficients was markedly higher for the hemodialyzer containing undulated fiber (0.968 vs. 0.496 for type A and type B, respectively). Conclusions The undulated-fiber type was found to have more uniform, consistent dialysate flow profiles. It is believed that this type of hemodialyzer will be found helpful for measurement and prescription of the delivered hemodialysis dose due to its better consistency.

Effects of arterial port design on blood flow distribution in hemodialyzers.

Background/Aims: Blood flow profiles in fiber bundles depend on the design of the arterial port and affects the biocompatibility of the hemodialyzer. We analyzed the effects of arterial port design on blood flow distribution in fiber bundles using nonintrusive imaging techniques. Methods: The velocity fields in arterial ports and the hemodynamics in fiber bundles were analyzed for hemodialyzers with different configurations using particle image velocimetry and perfusion computed tomography. Results: In a hemodialyzer with standard arterial ports, high blood flow profiles in the central and peripheral regions and low blood profiles in the middle region were developed due to jet flow and vortices around the jet. In a hemodialyzer with spiral arterial ports, higher flow profiles were developed due to the central vortices that decrease perfusion into the fiber bundles. Conclusion: The arterial port design of hemodialyzers should be optimized such that jet flow and vortices do not impair dialysis efficiency and biocompatibility.

Effects of dialysate flow configurations in continuous renal replacement therapy on solute removal: computational modeling.

Background/Aims: Continuous renal replacement therapy (CRRT) is commonly used for critically ill patients with acute kidney injury. During treatment, a slow dialysate flow rate can be applied to enhance diffusive solute removal. However, due to the lack of the rationale of the dialysate flow configuration (countercurrent or concurrent to blood flow), in clinical practice, the connection settings of a hemodiafilter are done depending on nurse preference or at random. Methods: In this study, we investigated the effects of flow configurations in a hemodiafilter during continuous venovenous hemodialysis on solute removal and fluid transport using computational fluid dynamic modeling. We solved the momentum equation coupling solute transport to predict quantitative diffusion and convection phenomena in a simplified hemodiafilter model. Results: Computational modeling results showed superior solute removal (clearance of urea: 67.8 vs. 45.1 ml/min) and convection (filtration volume: 29.0 vs. 25.7 ml/min) performances for the countercurrent flow configuration. Countercurrent flow configuration enhances convection and diffusion compared to concurrent flow configuration by increasing filtration volume and equilibrium concentration in the proximal part of a hemodiafilter and backfiltration of pure dialysate in the distal part. In clinical practice, the countercurrent dialysate flow configuration of a hemodiafilter could increase solute removal in CRRT. Nevertheless, while this configuration may become mandatory for high-efficiency treatments, the impact of differences in solute removal observed in slow continuous therapies may be less important. Under these circumstances, if continuous therapies are prescribed, some of the advantages of the concurrent configuration in terms of simpler circuit layout and simpler machine design may overcome the advantages in terms of solute clearance. Conclusion: Different dialysate flow configurations influence solute clearance and change major solute removal mechanisms in the proximal and distal parts of a hemodiafilter. Advantages of each configuration should be balanced against the overall performance of the treatment and its simplicity in terms of treatment delivery and circuit handling procedures.

Three-dimensional dialysate flow analysis in a hollow-fiber dialyzer by perfusion computed tomography.

Perfusion computed tomography (PCT) is a means to rapidly and easily evaluate cerebral perfusion in patients presenting with acute stroke symptoms, which provides insights into capillary-level hemodynamics. In this study, we used PCT to analyze the 3-dimensional dialysate flow in a low-flux hemodialyzer equipped with a standard fiber bundle. The dynamic CT studies were performed with 64-channel multi-detector row CT (MDCT) at a dialysate flow rate of 500 ml/min and a 1.0 ml/sec injection rate of contrast agent. Central volume principle was used to calculate hydrodynamic parameters by deconvolution of time-density curves (TDCs). Functional maps of dialysate flow (DF), dialysate volume (DV), and mean transit time (MTT) could quantitatively describe the dialysate flow maldistribution, variations in fiber packing, and perfusion pressure distribution in a hemodialyzer, respectively. PCT by means of analysis was able to overcome the limitations of conventional imaging techniques for analyzing dialysate flow distributions in hollow-fiber dialyzers. Not only local hydrodynamic phenomena at microscopic level but also macroscopic flow behavior of dialysate were visualized quantitatively. Therefore, we concluded that PCT is a quantitative analysis method to provide better insights into hydrodynamics of hollow-fiber dialyzers and is expected to contribute to optimization of artificial kidneys.

Development of a Cold Dialysate Regeneration System for Home Hemodialysis

Background/Aims: Because longer and/or more frequent dialysis has potential clinical benefits, home hemodialysis (HHD) systems should provide flexible renal replacement therapies. We propose a new cold dialysate regeneration system that requires 10 l per treatment for HHD. Methods: We designed a dialysate regeneration system using cold dialysate and 2 activated carbon columns alternatively switched between adsorption and desorption. Urea adsorption ratios were compared in three different conditions; cold dialysate (5.7°C), normal dialysate (36.8°C), and cold dialysate with washing. In vivo tests (n = 8) were conducted to validate this system. Results: The urea removal ratios were 20.0 ± 1.7% in cold dialysate, 36.0 ± 1.7% in normal dialysate, and 82.5 ± 1.2% in cold dialysate with washing. In animal experiments, the urea reduction ratio was 60.9 ± 6.3%, Kt/V was 1.0 ± 0.2, and serum electrolytes remained stable. Conclusion: The proposed cold dialysate regeneration system using a small volume of dialysate will be useful for HHD.

Computational modeling of effects of mechanical shaking on hemodynamics in hollow fibers

Introduction: Blood-membrane interaction during hemodialysis develops a secondary protein layer on the dialysis membrane surface, resulting in reduction of hemodialyzer performance. Wall shear stress at the surface of the hollow-fiber membrane is one of the determinant factors able to influence dialysis efficiency. Shaking of hemodialyzer during treatment could increase the wall shear stress of the membrane, which could enhance hemodialyzer performance. Methods: In this study, hemodynamic changes in hollow fibers were analyzed using computational fluid dynamics software for various shaking conditions of hemodialyzer (longitudinal, transverse, rotational motions). Results: Longitudinal motion induced reverse flow, while transverse motion induced symmetric swirling inside the hollow fiber. During rotational motions, nonuniform vortices were developed according to the rotational radius of the hollow fiber. These changes in flow pathlines induced by different shaking profiles increased the relative motion of blood, transmembrane pressure, and wall shear stress on dialysis membrane surfaces. Both longitudinal and transverse shaking profiles showed a linear relationship between shaking velocity (the product of amplitude and frequency) and wall shear stress. Conclusion: Performance of hemodialyzer can be enhanced with simple mechanical shaking motions, and optimal shaking profiles for clinical application can be investigated and predicted with the computational fluid dynamics model proposed in this study.

Analysis of Blood and Dialysate Flow in a Hemodialyzer by Perfusion Computed Tomography

Perfusion computed tomography (PCT) is a means to rapidly and easily evaluate cerebral perfusion in patients presenting with acute stroke symptoms, which pro-vides insights into capillary-level hemodynamics. In this study, we used PCT to analyze the 3-dimensional blood and dialysate flow in a low-flux hemodialyzer equipped with a standard fiber bundle. The dynamic CT studies were performed with 64-channel multi-detector row CT (MDCT) at a dialysate flow rate of 500 ml/min and a 1.0 ml/sec injection rate of contrast agent. Central volume principle was used to calculate hydro-dynamic parameters by deconvolution of time-density curves (TDCs). Functional maps of PCT parameters quantitatively described the blood and dialysate flow maldistribution, varia-tions in fiber packing, and perfusion pressure distribution in a hemodialyzer. PCT was able to overcome the limitations of conventional imaging techniques for analyzing dialysate flow distributions in hollow-fiber dialyzers. Therefore, PCT is a quantitative analysis method to provide better insights into hemodynamics of hollow-fiber dialyzers and is expected to contribute to optimization of artificial kidneys.