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A Receptor‐Based Bioadsorbent to Target Advanced Glycation End Products in Chronic Kidney Disease
Author(s) -
Zhang Yangrong,
Lapidos Karen A.,
GalMoscovici Anca,
Sprague Stuart M.,
Ameer Guillermo A.
Publication year - 2014
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/aor.12203
Subject(s) - glycation , chemistry , albumin , dialysis , kidney disease , medicine , receptor , serum albumin , peritubular capillaries , kidney , endocrinology , immunology
The accumulation of advanced glycation end products ( AGE s) has been reported to be a major contributor to chronic systemic inflammation. AGE s are not efficiently removed by hemodialysis or the kidney of a chronic kidney disease ( CKD ) patient. The goal of this study was to develop a receptor for AGE s ( RAGE )‐based bioadsorbent device that was capable of removing endogenous AGE s from human blood. The extracellular domain of RAGE was immobilized onto agarose beads to generate the bioadsorbent. The efficacy of AGE removal from saline, serum, and whole blood; biological effects of AGE reduction; and hemocompatibility and stability of the bioadsorbent were investigated. The bioadsorbent bound AGE ‐modified bovine serum albumin ( AGE ‐ BSA ) with a binding capacity of 0.73 ± 0.07 mg AGE ‐ BSA /mL bioadsorbent. The bioadsorbent significantly reduced the concentration of total AGE s in serum isolated from end‐stage kidney disease patients by 57%. AGE removal resulted in a significant reduction of vascular cell adhesion molecule‐1 expression in human endothelial cells and abolishment of osteoclast formation in osteoclast progenitor cells. A hollow fiber device loaded with bioadsorbent‐reduced endogenous AGE s from recirculated blood to 36% of baseline levels with no significant changes in total protein or albumin concentration. The bioadsorbent maintained AGE ‐specific binding capacity after freeze‐drying and storage for 1 year. This approach provides the foundation for further development of soluble RAGE ‐based extracorporeal therapies to selectively deplete serum AGE s from human blood and decrease inflammation in patients with diabetes and/or CKD .