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, Introduction Acute renal failure is manifested by the sudden cessation of renal function, retention of products of protein and mineral metabolism, alterations in fluid and acid-base homeostasis, and extremely high mortality. The latter has remained virtually unchanged over the last 30 years [1, 2], and has only been altered recently by advances in dialysis techniques [3] requiring large volumes of substitution fluid in the process of hemodiafiltration. The leading cause of acute renal failure and admission to the ICU in the USA is sepsis, with over 750,000 cases per annum an consisting of small proteins, and cytolkines involved in absolute mortality rate of 28.6%, and a projected annual 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. Copyright (C) 2003 S. Karger AG, Basel.

BACKGROUND Middle molecules such as beta2-microglobulin (beta2M) and advanced glycation end products (AGE)-modified proteins contribute to inflammation in uremia. The BetaSorb column is a new adsorptive device, which contains copolymeric beads, suitable for removal of beta2M and other middle molecules. We assessed the effect of this column on the bioreactivity of uremic plasma, as measured by cytokine responsiveness. METHODS Uremic plasma was perfused in vitro through the column (10 mL/min) and samples were collected after 10 to 30 passes. Endotoxin-stimulated tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production by THP-1-derived monocytes was measured following brief exposure to uremic plasma. beta2M levels were measured. The contribution of AGE-modified proteins to the bioreactivity of uremic plasma was explored. RESULTS TNF-alpha and IL-10 production markedly decreased after 30 passes (629 +/- 78 vs. 144 +/- 62 pg/mL; 207 +/- 25 vs. 117 +/- 23 pg/mL; P=0.04). The column removed beta2M efficiently with a marked decline in plasma levels by 99% after 30 passes. Neutralization of AGE receptor (RAGE) resulted in a further reduction in the bioreactivity of uremic plasma. This was observed with nonperfused, as well as perfused, uremic plasma, suggesting that AGE-modified proteins were biologically active and still present after perfusion. CONCLUSION The sorbent beads removed uremic solute(s) that prime monocytes to enhanced cytokine production. Removal of beta2M was efficient, and of native and AGE-modified middle molecules likely.

Recent technological advances have led to the development of a new adsorption column that allows removal of β-2 microglobulin (β2M) from the blood (BetciSorb™, RenalTech Int., New York, NY). The aim of this study was to assess the effect ot BetaSorb™ on the bioreactivity of uremic plasma mianly cytokine and hydrogen peroxide (H2O2) production by THP-1-moiiocytes. Plasma obtained pre dialysis from an ESRD patient at 5 distinct time points was used for in vitro perfusion experiments. Plasma was perfused over the column at a flow rate of 10 ml/min and samples were collected after 10, 20 and 30 passes. LPS-stimulated TNF-α and IL-10 production and H2O2 generation by THP-1-monocytes were measured following brief exposure to uremic plasma. β2M removal by the column was also examined. The column removed β2M efficiently as demonstrated by a marked decrease in β2M level by 91%, 98% and 99% after 10, 20 and 30 passes, respectively. Moreover, TNF-α and IL-10 production by THP-1-monocytes markedly decreased after 30 passes over the column while H2O2 production did not significantly change after 30 passes.TableThese results indicated that the BetaSorb™ perfusion column removes uremic solute(s) that prime monocytes to enhanced production of pro-inflammatory cytokines. Although this column is capable of removing β2M efficiently, studies are under way to elucidate mechanisms behind this drastic decline in cytokine production by monocytes after in vitro perfusion.

L'invention concerne des dispositifs et systemes multifonctionnels intraveineux, a demeure ou integres concus pour reduire les concentrations sanguines d'un composant cible par adsorption selective. Ces dispositifs et systemes peuvent etre utilises, par exemple pour reduire les concentrations sanguines de stimulateurs ou mediateurs pro-inflammatoires ou anti-inflammatoires par adsorption selective. Ces dispositifs et systemes sont utiles dans des situations ou des niveaux anormaux d'interactions non regulees ou excessives entre des stimulateurs ou des mediateurs pro-inflammatoires ou anti-inflammatoires sont atteints ou au cours d'evenements induisant ou pouvant induire une production anormale de stimulateurs ou de mediateurs pro-inflammatoires ou anti-inflammatoires. Ces dispositifs et systemes servent a prevenir, reguler, reduire ou attenuer la severite de la reponse inflammatoire et des etats pathologiques associes a des niveaux anormaux d'interactions non regulees ou excessives entre des stimulateurs ou des mediateurs pro-inflammatoires ou anti-inflammatoires.

A cluster of four cases of symptomatic B virus infection in humans occurred in Pensacola, Florida, in March 1987. Three cases occurred in persons who worked with monkeys at a research facility, and the fourth resulted from apparent autoinoculation through use of a nonprescription skin cream. Contact tracing identified 159 persons who may have been exposed to B virus (21 had been exposed to monkeys at the facility and 138 had been exposed to one or more of the case-patients), but no further cases were identified. Comparisons of restriction endonuclease patterns from B virus isolates linked two of the three cases in monkey handlers to one clinically ill monkey and the other to a second, healthy monkey. Three risk factors for human infection were identified: nonuse of mechanical or chemical restraints for monkeys before handling, nonuse of available protective gear, and direct viral inoculation through the application of a topical medication.