Albumin Dialysis MARS: Knowledge from 10 Years of Clinical Investigation STEFFEN R. MITZNER,* JAN STANGE,* SEBASTIAN KLAMMT,† SEBASTIAN KOBALL,* HEIKO HICKSTEIN,* AND EMIL C. REISINGER† A decade ago, albumin dialysis was introduced as a new extracorporeal detoxification method for patients with liver failure. Today, the molecular adsorbent recirculating system is the most frequently used type of albumin dialysis and most studied liver-support technique. Numerous preclinical and clinical studies demonstrated the importance of albumin as a scavenger for molecules with pathophysiological relevance in liver failure. Albumin dialysis enables the selective regenera- tion of albumin. The resulting increase of albumin binding capacity is paralleled by improvement of central and local hemodynamics and liver, brain, and kidney functions. The treatment can contribute to liver regeneration and prolonga- tion of patient survival in the context of acute liver failure, decompensated chronic liver disease, and bridging of patients to liver transplantation. Proper patient selection is critical for clinical success. Aggressive treatment of infections and sepsis seems to be a decisive prerequisite for its safe and efficient use. Cautious anticoagulation with heparin is the common standard. Citrate use is recommended for patients prone to bleeding. Taken together, albumin dialysis represents a valu- able therapeutic tool for the treatment of various types of liver failure. Ongoing and future studies will help define the optimal patient selection and technical process parameters such as session length and frequency of treatment. ASAIO Journal 2009; 55:498 –502. E arly generations of liver-support devices were limited in their therapeutic capacity mainly due to lack of efficacy (e.g., in systems using dialysis and hemofiltration) or selectivity (e.g., plasma exchange and plasma perfusion over sorbents). Espe- cially, the question of membrane structure and pore size in membrane-based methods is of concern. Removal rates for larger target substances increase with increasing pore size. However, selectivity decreases at the same rate and can result in loss of valuable plasma components such as regulator pro- teins of blood coagulation or growth hormones such as hepa- tocyte growth factor. Ho et al. 1 showed in an elegant plasma filtration study that survival dramatically decreases in animals with acute liver failure (ALF) if a regular pore size plasma filter is used, when compared with more selective filters. Another relevant aspect of low-selectivity systems is that they are typ- ically not suited for continuous treatment. This dilemma be- tween efficacy and selectivity, which prevented real clinical improvement of liver failure patients, prevailed until the mid- 90s. Introduction of liver cell bioreactors seemed to be an alternative worth studying. However, the observation that the most relevant liver failure toxins are small, hydrophobic mol- ecules dependent on transport by human serum albumin opened a new window of opportunity for the “artificial” liver- support systems. In the 1990s, several innovative approaches reached the level of clinical studies. The liver dialysis method of Ash et al. 2 works with a combination of membrane separation (using a dialysis membrane) and adsorption. The Prometheus System (fractionated plasma separation and adsorption) fol- lows a similar approach, although the separation membrane is more open (i.e., permeable for albumin), and the adsorption is done through fixed columns rather than a moving sorbent suspension. 3 Another technical approach to albumin cleansing is presented by a method called albumin dialysis. This tech- nology is based on the fact that albumin-bound substances (“liver toxins”) can be dialyzed through a regular dialysis membrane if the dialysate contains clean albumin as a molec- ular acceptor. Albumin dialysis is the first membrane-based liver support that allows maintaining the selectivity of a regular dialysis procedure by using a small pore membrane and effec- tive removal of even strongly albumin bound toxins. Two clinically usable modes of albumin dialysis are available to- day: the molecular adsorbent recirculating system (MARS) and single-pass albumin dialysis. 4 Molecular adsorbent recirculat- ing system has been available for broad clinical use since 1998 and is the best-studied albumin dialysis method at present time. It comprised a modified hemodialysis with a high-flux membrane, permitting passage of hydrophobic, albumin- bound target substances, and albumin-enriched dialysate. This albumin dialysate is on-line regenerated by passage through a second dialyzer and two adsorber columns (charcoal and anion exchanger) (Figure 1). 5 Clearance of Water-Soluble and Albumin-Bound Toxins The pattern of substances that can be removed from blood by albumin dialysis is much broader than that of hemodialysis, even if the identical type of dialysis membrane is used. Espe- cially, a significant removal of various albumin-bound metab- olites and drugs that accumulate in liver or kidney failure, enzyme defects such as protoporphyria, or drug overdose belong to this pattern. Substances that are bound to serum albumin and exert damaging effects in higher concentrations From the *Division of Nephrology, Department of Medicine, and †Division of Tropical Medicine and Infectious Diseases, Department of Medicine, University of Rostock, Rostock, Germany. Submitted for consideration August 2008; accepted for publication in revised form April 2009. Presented in part at the 54th Annual ASAIO Conference, June 19 – 21, 2008, San Francisco, CA. Reprint Requests: Steffen R. Mitzner, MD, Division of Nephrology, Department of Medicine, University of Rostock, E.-Heydemann-Str. 6, Rostock 18055, Germany. Email: steffen.mitzner@med.uni-rostock.de DOI: 10.1097/MAT.0b013e3181b37d86 ASAIO Journal 2009 498