Urinary β2-Microglobulin is a Sensitive Indicator for Renal Tubular Injury

Objective: After filtration through the glomeruli of the kidney, β2-microglobulin is reabsorbed by the renal proximal tubules. Increase in urinary β2-microglobulin indicates tubular dysfunction, and measurement of β2-microglobulin in urine sediment is useful to determine the source of kidney injury. CD133 has recently been characterized as a progenitor cell marker in the kidney, detecting injured epithelial cells in the proximal tubules. This study was designed to evaluate the correlation of increase in urinary β2-microglobulin and CD133 staining in patients with tubular injury. Methods: Between 2009 and 2012, 47 patients with renal biopsies had prior RenalVysion™ analysis. Among these, 30 patients had elevated urinary β2-microglobulin, the remaining 17 had normal range of urinary β2-microglobulin. Immunohistochemical staining for CD133 was performed in the corresponding renal biopsy specimens. Confluent CD133 staining in proximal tubules was considered positive. The correlation of urinary β2-microglobulin and CD133 staining was evaluated. Results: Of the 30 patients with elevated urinary β2-microglobulin, 26 showed positive CD133 staining in the proximal tubules. In 17 patients with normal urinary β2-microglobulin, 6 were positive for CD133 staining. Using positive CD133 staining as the end point, sensitivity was 86.6%, specificity was 64.7%, positive predictive value was 81.3%, and negative predictive value was 73.7%. Conclusion: Measurement of β2-microglobulin in urine is a sensitive assay to detect tubular injury, and strongly correlated with CD133 staining in injured renal proximal tubules. Due to low specificity, patients with elevated level of β2-microglobulin in urine should be evaluated in conjunction with the clinical history and urine cytological analysis, as well as urine and serum chemistry.