Proteomic-based identification of cleaved urinary β2-microglobulin as a potential marker for acute tubular injury in renal allografts

Our aim is to develop noninvasive tests to monitor the renal allograft posttransplant. Previously, we have reported that an unbiased proteomic-based approach can detect urine protein peaks associated with acute tubulointerstitial renal allograft rejection. Identification of these proteins peaks by mass spectrometry demonstrated that they all derive from nontryptic cleaved forms of beta 2-microglobulin. In vitro experiments showed that cleavage of intact beta 2-microglobulin requires a urine pH < 6 and the presence of aspartic proteases. Patients with acute tubulointerstitial rejection had lower urine pH than stable transplants and healthy individuals. In addition, they had higher amounts of aspartic proteases and intact beta 2-microglobulin in urine. These factors ultimately lead to increased amounts of cleaved urinary beta 2-microglobulin. Cleaved beta 2-microglobulin as an indicator of acute tubular injury may become a useful tool for noninvasive monitoring of renal allografts.