The Next Step from High-Flux Dialysis: Application of Sorbent Technology

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Abstract

The current foci of renal replacement therapy with dialysis are middle molecular weight toxins, consisting of small proteins, polypeptides and products of glycosylation and lipoxygenation. Conventional high-flux dialysis is not efficient at removing these molecules, explaining the increased interest in using sorbents to supplement dialysis techniques. Prototype biocompatible sorbents have been developed and investigated for middle molecule removal; these have been shown, in man, to remove β<sub>2</sub>-microglobulin, angiogenin, leptin, cytokines and other molecules, without reducing platelets and leukocytes. Extensive clinical studies are underway to demonstrate the clinical utility and safety of adding routinely a sorbent hemoperfusion device to hemodialysis.

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Design and statistical issues of the hemodialysis (HEMO) study.

Tom Greene, Gerald J Beck, Jennifer Gassman … (2000)

The Hemodialysis Study is a multicenter clinical trial of hemodialysis prescriptions for patients with end stage renal disease. Participants from over 65 dialysis facilities associated with 15 clinical centers in the United States are randomized in a 2 x 2 factorial design to dialysis prescriptions targeted to a standard dose or a high dose, and to either low or high flux membranes. The primary outcome variable is mortality; major secondary outcomes are defined based on hospitalizations due to cardiovascular or infectious complications, and on the decline of serum albumin. The Outcome Committee, consisting of study investigators, uses a blinded review system to classify causes of death and hospitalizations related to the major secondary outcomes. The dialysis dose intervention is directed by the Data Coordinating Center using urea kinetic modeling programs that analyze results from dialysis treatments to monitor adherence to the study targets, adjust suggested dialysis prescriptions, and assist in trouble-shooting problems with the delivery of dialysis. The study design has adequate power to detect reductions in mortality rate equal to 25% of the projected baseline mortality rate for both of the interventions.

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Oxidative Protein Damage with Carbohydrates and Lipids in Uremia: ‘Carbonyl Stress’

R Inagi, T. Miyata (1999)

Chronic uremia appears to be in a state of an increased oxidative stress. Under oxidative stress, proteins are modified directly by reactive oxygen species with the eventual formation of oxidised amino acids. Proteins are also modified indirectly with reactive carbonyl compounds formed by the autoxidation of carbohydrates and lipids, with the eventual formation of the advanced glycation/lipoxidation end products (AGEs/ALEs). AGEs, pentosidine and carboxymethyllysine (CML), and ALE, malondialdehyde (MDA)-lysine, are elevated in plasma and matrix proteins of uremic patients several times above normal subjects. Precursor carbonyl compounds derived from carbohydrates and lipids are indeed elevated in uremic circulation. Uremia thus appears to be in a state of carbonyl overload with potentially damaging proteins (carbonyl stress). Carbonyl stress might be relevant to long-term complications associated with chronic renal failure and dialysis, such as dialysis-related amyloidosis and atherosclerosis. Immunohistochemical studies identified carbonyl stress in long-lived amyloid deposits and vascular lesions. Proteins modified under carbonyl stress exhibit several biological activities, which might, at least in part, account for the development of joint and vascular complications in uremia.

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First Clinical Experience with an Adjunctive Hemoperfusion Device Designed Specifically to Remove β 2 -Microglobulin in Hemodialysis

Claudio Ronco, Alessandra Brendolan, James F Winchester … (2001)

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Author and article information

Journal

Journal ID (publisher-id): BPU

Journal ID (nlm-ta): Blood Purif

Journal ID (doi): 10.1159/issn.0253-5068

Title: Blood Purification

Publisher: S. Karger AG

ISBN: 978-3-8055-7372-6

ISBN: 978-3-318-00813-5

ISSN (Print): 0253-5068

ISSN (Electronic): 1421-9735

Publication date Subscription-year: 2002

Publication date (Print): 2002

Publication date (Electronic): 17 January 2002

Volume: 20

Issue: 1

Pages: 81-86

Affiliations

^aRenalTech International, New York, N.Y., USA; ^bOspedale San Bortolo, Vicenza, Italy; ^cVeterinary Medicine Teaching Hospital, University of California Davis, Sacramento, Calif., USA; ^dRussian Academy of Sciences (INEOS), Moscow, Russia; ^eUniversity of Vienna, Austria; ^fUniversity of California San Francisco, Calif., USA and ^gRenal Research Institute, New York, N.Y., USA

Article

Publisher ID: 46989 Other ID: Blood Purif 2002;20:81–86

DOI: 10.1159/000046989

PubMed ID: 11803163

SO-VID: 0bf95180-fce9-49a1-a95e-fd85c4f112c8

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The Next Step from High-Flux Dialysis: Application of Sorbent Technology

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Karger: Nephrology

Most cited references 5

Design and statistical issues of the hemodialysis (HEMO) study.

Oxidative Protein Damage with Carbohydrates and Lipids in Uremia: ‘Carbonyl Stress’

First Clinical Experience with an Adjunctive Hemoperfusion Device Designed Specifically to Remove β 2 -Microglobulin in Hemodialysis

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