Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods

Purpose: Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals. Experimental design: The study included 34 renal transplant patients with histologically proven CAN and 36 patients with normal renal transplant function. High-throughput proteomic profiles were generated from urine samples with three different ProteinChip arrays by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Following SELDI, a biomarker pattern software analysis was performed which led to the identification of a novel biomarker pattern that could distinguish patients with CAN from those with normal renal function. Results: An 11.7 kDa protein identified as beta 2 microglobulin was the primary protein of this biomarker pattern, distinguishing CAN from control patients (receiver operator characteristic [ROC] = 0.996). SELDI-TOF-MS comparison of purified beta 2 microglobulin protein and CAN urine demonstrated identical 11.7 kDa protein peaks. Significantly, higher concentrations of 2 microglobulin were found in the urine of patients with CAN compared with the urine of normal renal function transplant recipients (p<0.001). Conclusions and clinical relevance: Although further validation in a larger more diverse patient population is required to determine if this beta 2 microglobulin protein biomarker will provide a potential means of diagnosing CAN by noninvasive methods in a clinical setting, this study clearly shows a capability to stratify control and disease patients.