In vitro Removal of Protein-Bound Retention Solutes by Extracorporeal Blood Purification Procedures.

INTRODUCTION: When the kidneys or liver fail, toxic metabolites accumulate in the patient's blood, causing cardiovascular and neurotoxic complications and increased mortality. Conventional membrane-based extracorporeal blood purification procedures cannot remove these toxins efficiently. The aim of this in vitro study was to determine whether commercial hemoperfusion adsorbers are suitable for removing protein-bound retention solutes from human plasma and whole blood as well as to compare the removal to conventional hemodialysis. METHODS: For in vitro testing of the removal of protein-bound substances, whole blood and plasma were spiked with uremic retention solutes (homocysteine, hippuric acid, indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid) and the toxins of liver failure (bilirubin, cholic acid, tryptophan, phenol). Subsequently, the protein binding of each retention solute was determined. The adsorption characteristics of the hemoperfusion adsorbers, Jafron HA and Biosky MG, both approved for the adsorption of protein-bound uremic retention solutes and Cytosorb, an adsorber recommended for adsorption of cytokines, were tested by incubating them in spiked whole blood or plasma for 1 h. Subsequently, the adsorption characteristics of the adsorbers were tested in a dynamic system. For this purpose, a 6-h in vitro hemoperfusion treatment was compared with an equally long in vitro hemodialysis treatment. RESULTS: Hippuric acid, homocysteine, indoxyl sulfate, and tryptophan were most effectively removed by hemodialysis. Bilirubin and cholic acid were removed best by hemoperfusion with Cytosorb. A treatment with Jafron HA and Biosky MG showed similar results for the adsorption of the tested retention solutes and were best for removing phenol. 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid could not be removed with any treatment method. DISCUSSION/CONCLUSION: A combination of hemodialysis with hemoperfusion seems promising to improve the removal of some toxic metabolites in extracorporeal therapies. However, some very strongly protein-bound metabolites cannot be removed adequately with the adsorbers tested.

Particle leakage in extracorporeal blood purification systems based on microparticle suspensions.

AIM: The newly developed 'Microspheres based Detoxification System' (MDS) designed for any extracorporeal adsorption therapy uses microparticles as adsorbents characterized by a size of 1-20 microm in diameter which are recirculated in the secondary (filtrate) circuit connected to a hollow fiber filter located in the primary (blood) circuit. In the case of a leakage or rupture in the hollow fiber filter, microspheres can enter patients' blood circuits and cause embolic episodes in different organs with varying degrees of clinical relevance. Aim of this study was to determine the amount of particles infused to a patient during a long-term treatment under different failure conditions of the filter. METHODS: The filters were prepared by cutting single hollow fibers. Fresh-frozen plasma (FFP) and a mixture of glycerol and water were used as a medium together with microparticles potentially used in the MDS. The amounts of particles transferred from the filtrate into the primary circuit were measured. RESULTS: The analysis of particle transfer in the case of a single cut hollow fiber inside the membrane results in particle volumes of up to 26 ml calculated for 10 h. CONCLUSION: Particle leakage in microparticle suspension based detoxification systems can lead to considerable particle transfer to the patient. Therefore, a particle detection unit which is able to detect critical amounts of particles (<1 ml particle volume/treatment) in the extracorporeal blood line is necessary for patient safety.