Background Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome (NS).However,it is invasive,time-consuming and can not be performed frequent on the same patient.Thus,development of a non-invasive and rapid diagnostic method may improve clinical patient management.Methods Proteomic tool magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MB-based MALDI TOF MS) was applied to serum to determine peptidome patts that are characteristic of different pathological changes.Results Serum specimen from 114 patients with NS (62 were minimal change disease (MCD),30 were membranous nephropathy (MN),and 22 were focal segmental glomerulosclerosis (FSGS)) and 60 normal individuals were analyzed using MB-based MALDI TOF MS.The peptidome patt was generated by genetic algorithms using a training set of 31 MCD,15 MN,11 FSGS and 30 normal individuals and was validated by an independent testing set of the remaining samples.The serum peptidome patt,based on a panel of 14 peaks,accurately recognized samples from MCD,MN,FSGS and healthy control with sensitivities of 93.5％,86.7％,63.6％ and 90.0％,and specificities of 98.2％,94.4％,100％and 89.5％,respectively.Moreover,one peptide from peptidome patt was identified by liquid chromatography tandem mass spectrometry (LC MS/MS) as fibrinogen A.Conclusion Detection of the serum peptidome patt is a rapid,non-invasive,high-throughout,and reproducible method for identifying the pathological patts of patients with nephrotic syndrome.