ABSTRACT
Renal replacement therapy in acute renal failure (ARF) and chronic renal failure (end-stage renal disease; ESRD) has been based on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle-molecular-weight toxins, consisting of low-molecular-weight proteins and peptides (LMWP) and cytokines involved in inflammation. High-flux dialyzers are not efficient at removing LMWP, and for this reason, sorbents have been studied to augment or replace dialysis. Removal of LMWP such as beta2-microglobulin, leptin, complement factor D, angiogenin and cytokines such as interleukin (IL)-1, IL-6, IL-10, IL-18 and tumor necrosis factor-alpha has been established in animal models of sepsis and in ESRD patients using sorbents. Sorbent devices added to hemodialysis, or the use of such devices alone in inflammatory states, including sepsis, ARF, cardiopulmonary bypass, pre-explantation of donor organs and ESRD, are being studied.
Subject(s)
Acute Kidney Injury/therapy , Cytokines/blood , Hemoperfusion/methods , Kidney Failure, Chronic/therapy , Resins, Synthetic , Acute Kidney Injury/blood , Adsorption , Adult , Animals , Blood Proteins/metabolism , Clinical Trials as Topic , Female , Humans , Inflammation/blood , Kidney Failure, Chronic/blood , Male , Middle Aged , Molecular Weight , Peptides/blood , Resins, Synthetic/chemistry , Sepsis/blood , Sepsis/therapy , Treatment OutcomeABSTRACT
Beta-2 microglobulin is the most widely studied low-molecular-weight protein in end-stage renal disease. It is known to cause dialysis-related amyloidosis (DRA), by virtue of its retention when renal function fails, its deposition in tissues, its aggregation into fibrils, and its ability to become glycosylated. The onset of DRA may be protracted by the use of noncellulosic membranes, especially when high-volume hemodiafiltration is used in the treatment of renal failure. Adsorptive methods have been developed to improve the removal of beta-2 microglobulin. There seems to be a relative risk reduction in mortality when patients are treated with dialysis membranes that have a higher clearance of beta-2 microglobulin.
Subject(s)
Kidney Failure, Chronic/metabolism , beta 2-Microglobulin/metabolism , Amyloidosis/etiology , Amyloidosis/metabolism , Arteriosclerosis/etiology , Arteriosclerosis/metabolism , Glycation End Products, Advanced/metabolism , Humans , Inflammation/etiology , Inflammation/metabolism , Kidney Failure, Chronic/mortality , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/urine , Kinetics , Renal Dialysis/adverse effects , Renal Dialysis/methods , Uremia/complicationsSubject(s)
Dialysis Solutions/pharmacology , Peritoneal Dialysis, Continuous Ambulatory/methods , Adsorption , Automation , Biocompatible Materials , Cation Exchange Resins/pharmacology , Charcoal/pharmacology , Dialysis Solutions/pharmacokinetics , Female , Hemofiltration , Humans , Kidney Failure, Chronic/therapy , Male , Particle Size , Sensitivity and Specificity , Treatment OutcomeABSTRACT
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.
