A pilot study to investigate the potential of mass spectrometry profiling in the discovery of novel serum markers in chronic renal disease

Abstract

There has been significant criticism of how technologies such as SELDI have been used in biomarker discovery and how the data have been analysed. We initiated a proof-of-principle pilot study using SELDI with stringent pre-analytic and analytical procedures with robust statistical analysis, to determine whether, under such conditions, using different degrees of renal dysfunction as a model, useful data could be obtained. SELDI-TOF-MS profiling with stringent quality control measures was used to examine the proteomic profile of serum from healthy controls (n=30), patients with end-stage renal failure being treated by dialysis (n=30) and renal transplant patients (n=50) with varying degrees of graft stability. Principal component analysis of the data suggests that the continuum from normality to end-stage renal failure through 'stable' and 'unstable' transplant may be detected by SELDI profiling. Serum β2 microglobulin was identified as a major component and this was validated using immunonephelometry. This pilot study suggests that stringently controlled SELDI analysis is able to detect proteins which may be useful in the stratification of patients post-renal transplant. Further studies using a larger cohort of patients with chronic allograft dysfunction, defined by protocol biopsies, are indicated.