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J Am Soc Nephrol 13:S72-S77, 2002
© 2002 American Society of Nephrology

Hemodialysis

ß2-Microglobulin Amyloidosis: Effects of Ultrapure Dialysate and Type of Dialyzer Membrane

Gerhard Lonnemann and Karl M. Koch

Department of Nephrology, Medizinische Hochschule Hannover, Hannover, Germany

Address correspondence to Dr. Gerhard Lonnemann, Gemeinschaftspraxis, Eickenhof 15, D-30851 Langenhagen, Germany. Phone: +49-511-7865621; Fax: +49-511-7865625; E-mail: GLonnemann{at}t-online.de

Abstract

ABSTRACT. The available data on the pathophysiology of ß2-microglobulin amyloidosis (ß2mA) suggest that this progressive disease associated with end-stage renal failure develops in several consecutive phases. First, declining kidney function leads to retention of ß2 microglobulin (ß2m) and its deposition preferentially in the synovial tissue of bigger joints such as wrists, shoulders, and hips. Second, at the site of deposition, formation of unique amyloid fibrils, whose major component is ß2m, takes place. Deposition and fibril formation occur in the absence of modification of ß2mA by advanced glycoxidation end products and also in the absence of a local inflammatory response. It is later, in the third phase, that advanced glycoxidation end product modification of ß2m induces a local inflammatory response by attracting macrophages chemotactically and by stimulating these cells to produce and release proinflammatory cytokines. In addition, unmodified ß2m itself induces inflammatory activities such as upregulation of cyclooxygenase-2 and metalloproteinase-1. The severity of the local inflammation seems to determine the degree of the destructive processes in tissue and bone accompanying ß2mA.




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