Peritoneal dialysis appears to be a promising therapeutic tool for patients affected by refractory CHF. Clinical improvement of cardiac function may be related to clearing blood from middle molecular weight myocardial depressant substances, including atrial natriuretic peptide. Prospective multicentre trials are needed to confirm these encouraging results.

No abstract

The application of extracorporeal blood circuits in liver failure therapy has its roots in the two functions of the liver, first as a detoxifying and second as a synthetizing organ. In contrast to hydrophilic uremic toxins, most liver toxins are hydrophobic and bind preferentially to blood proteins. Consequently, the majority of these compounds cannot be removed by hemodialysis or similar dialytic procedures. Current systems use albumin as a transport vehicle for hydrophobic compounds across high flux membranes (e.g. albumin-dialysis, molecular adsorbent recirculating system (MARS)). In contrast to these devices, the Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) applies filtration across highly permeable membranes with a molecular weight cut-off of >300.000. These membranes facilitate a direct filtration of most of the toxin-bearing proteins. In a secondary circuit these toxins are then removed by adsorber beads assembled in specially designed cartridges. The protein-containing toxin-free solution returns to the primary circuit. Clinical testing of the Prometheus system's safety and efficacy parameters showed that cell counts and coagulation factors were not significantly affected. Total bilirubin-, bile acid- and plasma ammonia-levels were reduced in vivo by -21%, -43% and -40%, respectively. First successful therapeutic results have been obtained for patients treated for drug abuse and for patients waiting for transplantation. Thus, a combination of plasma fractionation with highly permeable membranes followed by a secondary circuit with adsorber cartridges proves to be the most effective method of removing toxic waste in liver failure. Further investigations will follow in order to extend the application of the Prometheus system to larger cohorts of patients.

The parameters of a two-pool model of beta2-m kinetics can be derived from concentration profiles obtained under routine dialysis conditions, but accuracy is not completely satisfactory. Similar to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2-m) can be calculated from the pre- and post-dialysis concentrations of beta2-m, body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the maximum possible removal of beta2-m in HD with three sessions per week.

Initial results of the clinical use of primary porcine liver cells for extracorporeal liver support are being reviewed as the cell source is controversial. According to Eurotransplant data 20 −25% of explanted donor livers are not transplanted, due to factors such as steatosis or cirrhosis. This number corresponds to the number of patients with acute liver failure who require bridging therapy to transplantation. Primary human liver cells from transplant discards can be isolated, purified and maintained in bioreactors and provide an alternative for cell-based extracorporeal liver support therapy. A four-compartment bioreactor enables recovery from preservation and isolation injury in a three-dimensional network of interwoven capillary membranes with integrated oxygenation, rendering the liver cells from these discarded donor organs viable for clinical utilization. Patient contact with additional animal-derived biomatrix and fetal calf serum can be avoided. The initiation of an in vitro cultivation phase allows cell stabilization, quality control, and immediate availability of a characterized system without cryopreservation. The hypothesis of this paper is that with appropriate logistics and four-compartment bioreactor technology, cells from human liver transplant discards can serve the demand for cell-based therapy, including extracorporeal liver support.