Semipermeable hollow-fiber dialyzers currently represent the standard of care for IHD or CRRT for patients with AKI. All dialyzer membranes induce some degree of activation of blood components, a phenomenon called bioincompatibility. 691 Earlier-generation dialyzer membranes composed of cuprophane or unmodified cellulose were more bioincompatible and had the potential to cause a ‘‘dialyzer membrane reaction’’, mediated by complement activation, release of proinflammatory markers, and oxidative stress, and manifested clinically by acute hypotension, vasodilatation, leucopenia, hypoxia and fever.692-697 More recently, modified cellulosic membranes (with substitution of the hydroxyl groups) and synthetic membranes composed of polyacylnitrile, polysulfone, or poly(methyl methacrylate) have been developed. These ‘‘biocompatible membranes’’ (or less bioincompatible membranes) produce less complement and cytokine activation, and decrease oxidative stress.697,698 Recent studies suggest that platelet activation might also be involved in the bioincompatibility phenomenon.698-701 Another membrane characteristic that might have clinicalimportance is the flux property, with membranes generally being divided in low-flux and high-flux, the latter having larger pores and thus the potential to clear larger solutes. The question of whether membrane bioincompatibility or flux has clinical relevance in the setting of AKI has been the subject of many clinical trials. A recent meta-analysis of 10 randomized or quasi-randomized controlled trials in 1100 patients could not establish any advantage for biocompatible or high-flux membranes.702 Of note, the authors chose to include modified cellulose membranes in the bioincompatible group, although other investigators consider modified cellulosic membranes to be biocompatible. When comparing the synthetic membranes to cuprophane, there was a trend towards reduced mortality with the synthetic membranes. This meta-analysis also did not assess the side-effects of different membrane compositions on more proximal, temporal associations, such as acute hypotension or fever. As a result, we agree with the authors’ conclusion that the use of either a biocompatible or modified cellulose acetate membrane appears to be appropriate.
Recent observations reveal specific potential side-effects when using certain dialyzer membranes. Bradykinin release syndrome has been observed at the start of CRRT with uncoated AN-69 membranes.703 Bradykinin release syndrome is characterized by acute hypotension and pulmonary vascular congestion. The syndrome is usually self-limited and is pH-dependent, and therefore more pronounced in patients with severe acidosis. Also, priming of the circuit with banked blood (that is acidotic and contains a large amount of citrate, inducing hypocalcemia) may evoke bradykinin release syndrome. Numerous measures have been published to prevent or mitigate this syndrome, including zero-balance HF to normalize the banked blood pH and calcium,704 or a bypass maneuver in which the blood prime is given to the patient instead of the circuit, while the patient is bled on to the circuit with the saline prime discarded.705 Finally, a form of bradykinin release syndrome has been reported in patients receiving ACE-I and IHD with AN-69 membranes,706-708 since ACE-I prevent the conversion of bradykinin and thereby prolong the hypotensive response when acidic blood comes in contact with the AN-69 membrane. However, others have disputed this interaction.704,705 Nevertheless, clinicians should be aware of the potential for bradykinin release syndrome if an uncoated AN-69 membrane is employed for RRT, especially in acidotic patients or in those receiving ACE-I. Neutralizing the electronegativity of the AN-69 membrane by coating with polyethyleneimine significantly reduces bradykinin generation.709
Whether conventional dialysis membranes are able to affect clinical outcomes in sepsis by removal of inflammatory mediators remains highly controversial. Until further evidence becomes available, the use of RRT to treat sepsis should be considered experimental.