Sorbents in Acute Renal Failure and the Systemic Inflammatory Response Syndrome

Abstract

Renal replacement therapy in acute renal failure is currently focused on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle molecular weight toxins, consisting of small proteins, and cytokines involved in the systemic inflammatory response syndrome (SIRS). Conventional high-flux dialyzers are not efficient at removing these molecules, prompting the investigation of sorbents to augment or replace dialysis. Sorbents have been developed to modulate SIRS by targeting cytokines such as IL-1, IL-6, IL-10, IL-18 and TNF, among others. Extensive pre-clinical studies are underway to demonstrate the clinical utility and safety of either adding sorbent hemoadsorption devices to hemodialysis, or the use of such devices alone in SIRS, sepsis, acute renal failure, cardiopulmonary bypass and end-stage renal disease.

Detrimental Cross-Talk Between Sepsis and Acute Kidney Injury: New Pathogenic Mechanisms, Early Biomarkers and Targeted Therapies

“…Most of these devices are designed to combine the adsorption strategy with standard RRT. The biocompatibility of these devices is the main limitation for their use and thrombocytopenia and bleeding risk are the most relevant adverse effects [43]. Polymyxin B (PMX-B) is a cationic polypeptide antibiotic with activity against Gram-negative bacteria and high affinity for endotoxin, but its intravenous use has been limited due to the wellknown nephrotoxicity and neurotoxicity.…”

Clinical review: Blood purification for sepsis

“…The sorbent attracts solutes through hydrophobic interactions, ionic attraction, hydrogen bonding, and van der Waals interactions [41]. Until recently, poor biocompatibility has been the main clinical limitation of hemoadsorption, as evidenced by severe thrombocytopenia and leukopenia [41].…”

“…The sorbent attracts solutes through hydrophobic interactions, ionic attraction, hydrogen bonding, and van der Waals interactions [41]. Until recently, poor biocompatibility has been the main clinical limitation of hemoadsorption, as evidenced by severe thrombocytopenia and leukopenia [41]. The interesting feature of hemoadsorption is its high-molecular-weight adsorption potential, allowing it to target large molecules, exceeding the cutoff of conventional synthetic high-flux hemofilters.…”

Cytokine Removal with a Novel Adsorbent Polymer

“…The most likely mechanisms include hydrophobic interactions, ionic or electrostatic attractions, hydrogen bonding and van der Waals' interactions [17]. However, the influence of temperature and Ca 2+ on the adsorption is not known.…”