Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling

Abstract

BackgroundIgA 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.MethodsWe 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.ResultsWe 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.ConclusionsIn 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.

α‐1‐Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression

“…It is a glycoprotein with a broad range of activities, including the downregulation of neutrophil elastase during the inflammatory processes. Kwak et al recently evaluated this protein expression in renal biopsies [6], while other authors independently described its overexcretion in the urine of some patients with primary GNs, most specifically FSGS, IgAN, and minimal change disease [7][8][9]. The IHC staining against A1AT demonstrated its localization in the cytoplasm of podocytes present in sclerotic glomeruli.…”

Biomarkers in IgA nephropathy: relationship to pathogenetic hits

“…For example, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis identified a fragment of uromodulin, m/z 1913.14, in urine samples that showed an area under the curve (AUC) of 0.998 for distinguishing patients with IgA nephropathy from healthy controls and of 0.815 from patients with other glomerulopathies [87]. MALDI-TOF MS analysis of urine samples from 19 patients with IgA nephropathy and 14 healthy controls found 16 IgA nephropathy-associated peptides, including uromodulin ( m/z 1913) [88]. …”

Biomarker Characterization by MALDI–TOF/MS

“…Three peptides that strongly correlated with glioma were identified [243]. Serum peptide and protein profiling using magnetic beads/MALDI-TOF/MS for disease diagnosis have also been reported to diagnose hepatocellular carcinoma [244], CRC [245], schizophrenia [246], IgA nephropathy [247], biliary tract cancer [248], and inflammatory bowel diseases [249]. Moreover, this approach was used to obtain saliva peptide profiles for diagnosing primary Sj€ ogren's syndrome [250] and urine peptide profiles for diagnosing endometriosis [251].…”