Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification. Methods. We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis. Results: We identified 55 peptides - 13 in serum, 26 in plasma, and 16 in urine - that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings - ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury.We also identified 3 peptides - corresponding to bradykinin, uromodulin, and alpha-1-antitrypsin - that were associated with severity of lesions, such as tubulointerstitial damage and segmental glomerulosclerosis.Moreover, blood peptides with m/z 2953, 5337, 9287, and 9289 and urine peptides with m/z 1769, 1898, 1913, 1945, 2491, 2756, 2977, 3004, 3389, and 4752 correlated significantly with poor renal function. Conclusions: In patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients. © 2013 Graterol et al.; licensee BioMed Central Ltd.