Interaction between beta 2-microglobulin and advanced glycation end products in the development of dialysis related-amyloidosis
Department of Medicine, Division of Rheumatology
Amyloidosis; Collagen; Glycosylation; Glycosylation End Products, Advanced; Humans; Kidney Failure, Chronic; Renal Dialysis; beta 2-Microglobulin
Female Urogenital Diseases and Pregnancy Complications | Male Urogenital Diseases
Dialysis related amyloidosis (DRA) is a progressive debilitating complication of long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs preferentially in older patients and initially is located in collagen-rich osteo-articular tissues. Since an age-dependent increase in the formation of advanced glycation end products (AGE) has been observed in collagen-containing structures, we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed locally in osteo-articular structures as a subsequent event of its binding to collagen-AGE. Based on this hypothesis, we investigated the binding between beta 2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to collagen-AGE was dependent on the concentrations of both beta 2m and of AGE contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta 2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation during three weeks of incubation with physiologic concentrations of glucose. Similar processes in vivo may be important in the pathobiology of DRA.
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Citation: Kidney Int. 1997 May;51(5):1514-9.
Hou, Fan Fan; Chertow, Glenn M.; Kay, Jonathan; Boyce, Joshua; Lazarus, J. Michael; Braatz, James A.; and Owen, William F. Jr., "Interaction between beta 2-microglobulin and advanced glycation end products in the development of dialysis related-amyloidosis" (1997). Rheumatology Publications and Presentations. 80.