Role of β2-microglobulin in uremic patients may be greater than originally suspected.

The role of beta2-microglobulin (β2M) in dialysis-related amyloidosis as a specific amyloid precursor was defined in the 1980s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association between β2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular (CV) and/or mortality risk have grown. In the current literature, clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the high-risk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.