Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

Abstract

There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

Age‐Dependent Changes of Kidney Injury Biomarkers in Pediatrics

“…Serum beta‐2 microglobulin is independent from muscle mass, and the production of this protein is increased during infection and inflammatory processes . Recent research showed that serum beta‐2 microglobulin to assess glomerular filtration function might be less favorable in pediatric populations as compared to adults . However, urinary beta‐2 microglobulin might be more useful since beta‐2 microglobulin is removed from the serum by glomerular filtration, but almost all of the filtered protein is reabsorbed in the proximal tubule.…”

“…31 Recent research showed that serum beta-2 microglobulin to assess glomerular filtration function might be less favorable in pediatric populations as compared to adults. 38 However, urinary beta-2 microglobulin might be more useful since beta-2 microglobulin is removed from the serum by glomerular filtration, but almost all of the filtered protein is reabsorbed in the proximal tubule. This results in a minimal urinary beta-2 microglobulin concentration.…”

Effect factors related to a high probability of hemodialysis independence in newly diagnosed multiple myeloma patients requiring hemodialysis

“…26,27 Recent studies discovered that β 2 M is not only a biomarker in patients with chronic kidney disease and endstagerenaldisease,butalsoapromisingmarkertoassessglomerular and tubular function in adults. 28 However, our study first found the role of β 2 M in the reversal of renal failure and recovery from dialysis dependence.…”

Identification of key proteins involved in stickleback environmental adaption with system-level analysis

“…All four fingerprint proteins of the LS population are functionally important during inflammation, suggesting that an inflammatory response is activated in gill tissue of the LS population. Caspase 1 (G3P6H8) is part of the inflammsome complex 11 , beta-2-microglobulin (G3Q6I1) is a common inflammatory protein that has been used as a biomarker of inflammation associated with human diseases 12 , metalloendopeptidases (inlc. choryolysin L-type, G3PN26) are potant targets of anti-inflammatory drugs 13 , and sphingomyelin phosphodiesterases (incl.…”