BACKGROUND: IgA nephropathy (IgAN) is the most prevalent type of primary glomerular disease (PGD) worldwide. Currently, prognosis of PGD is predicted depends on estimated glomerular filtration rate (eGFR) and the degree of proteinuria. However, these physiological parameters may be varied and not sensitive enough to predict prognosis and treatment outcomes. Therefore, it is necessary to identify novel biomarkers to guide therapeutic decisions. METHODS AND RESULTS: Using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled two‑dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS), we quantified a total of 581 proteins in all renal biopsy specimens of 54 IgAN patients who were given, on a randomized basis, either traditional Chinese medicine (TCM) or combined corticosteroids and TCM (CT) therapy. 6 modules of co-expressed networks were revealed by using weighted gene co-expression network analysis (WGCNA). Of these, 4 modules correlated with baseline eGFR (1 negatively, and 3 positively) or change in eGFR between baseline and 12-month follow-up (3 negatively, and 1 positively). Multiple linear regression models were applied to assess effects of individual proteins on treatment outcomes in patients with IgAN. After adjustment for potential confounders, including baseline eGFR, age, and gender, expression levels of 32 proteins in kidney were significantly (p<0.05) associated with change in eGFR between baseline and 12-month follow-up in CT treatment group (16 positive, 16 negative). CONCLUSIONS: We constructed the renal protein co-expression networks for IgAN patients which can be correlated with clinicopathological features and prognosis. The proteins associated with treatment outcomes of CT therapy in IgAN patients may serve as potential markers to guide medical decision making.