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

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 (beta M-2) 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 beta M-2, 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 beta M-2 function arise as a result of altered binding of beta M-2 to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of beta M-2 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 beta M-2 may be a marker for glomerular rather than tubular pathology. We review the existing literature about beta M-2 as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that beta M-2 is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of beta M-2 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 beta M-2 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.