Complement Activation by Activated Carbon Adsorbents

Acute renal failure (ARF) is a condition that affects up to 20% of patients on intensive care units (ICU). Although the most common causes of ARF are sepsis and septic shock [1], acute loss of renal function may also occur following surgery or as a result of trauma, burns or the use of nephrotoxic drugs [2]. Conventional treatment of ARF includes drug therapy in combination with extracorporeal renal replacement therapies such as continuous haemodialysis and haemofiltration. Such extracorporeal therapy consists of a circuit containing a filter through which blood is passed for the removal of low molecular weight uraemic toxins. The retained components of the blood, such as cells and proteins, are rehydrated with isotonic replacement solutions before being returned to the body [3,4,5]. A combination of the conventional filtration-based therapies with adsorptive technology may allow more efficient removal of molecules and complexes that are unable to pass through conventional membranes. However, contact between blood and foreign surfaces such as carbon adsorbents may result in further activation of the body's defence systems. One important component of this defence mechanism is the complement cascade which in turn leads to secondary inflammatory events [6]. The haemoperfusion columns currently available use adsorbents coated with a semi-permeable layer of polymer such as cellulose to improve their biocompatibility. However this coating strongly reduces the adsorptive properties of the material for molecules in the high molecular weight and middle molecule range as it acts as a barrier for the free diffusion of molecules to the carbons [7]. It is clear, therefore, that the development of bio/haemocompatible uncoated adsorbents, which show superior adsorption capacity for a range of molecules, would significantly improve the capabilities of current renal replacement therapies.