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Urinary prognostic biomarkers and classification of IgA nephropathy by high resolution mass spectrometry coupled with liquid chromatography.

ABSTRACT: IgA nephropathy is the most common cause of primary glomerulonephritis. There are different pathologic biopsy-based scoring systems in use, but there is no consensus among nephrologists yet regarding the best classification method. Our aim was to test urine proteomics as a non-invasive method for classification of IgA nephropathy. This aim was pursued by discovering novel prognostic protein biomarkers in urine, and linking them to pathogenesis of the disease through known signaling and metabolic pathways. 13 urine samples of the patients with biopsy-proven IgA nephropathy were analyzed via two proteomics approaches: nanoflow LC-MS/MS and GeLC-MS/MS. The results of label-free quantification were subjected to multivariate statistical analysis, which could classify patients into two groups, broadly corresponding to the primary and advance stages. The proteome classification correlated well with biopsy-based scoring systems, especially endocapillary hypercellularity score of the Oxford's classification. Differentially excreted candidate proteins were found as potential prognostic biomarkers: afamin, leucine-rich alpha-2-glycoprotein, ceruloplasmin, alpha-1-microgolbulin, hemopexin, apolipoprotein A-I, complement C3, vitamin D-binding protein, beta-2-microglobulin, and retinol-binding protein 4. Pathway analysis suggested impairment of Extra Cellular Matrix (ECM)-Receptor Interaction pathways as well as activation of complement and coagulation pathway in progression of IgA nephropathy.

SUBMITTER: Kalantari S

PROVIDER: S-EPMC3855054 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Urinary prognostic biomarkers and classification of IgA nephropathy by high resolution mass spectrometry coupled with liquid chromatography.

Kalantari Shiva S Rutishauser Dorothea D Samavat Shiva S Nafar Mohsen M Mahmudieh Leyla L Rezaei-Tavirani Mostafa M Zubarev Roman A RA

PloS one 20131205 12

IgA nephropathy is the most common cause of primary glomerulonephritis. There are different pathologic biopsy-based scoring systems in use, but there is no consensus among nephrologists yet regarding the best classification method. Our aim was to test urine proteomics as a non-invasive method for classification of IgA nephropathy. This aim was pursued by discovering novel prognostic protein biomarkers in urine, and linking them to pathogenesis of the disease through known signaling and metabolic ...[more]

PMID: 24339887

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Project description:Background. MicroRNAs (miRNAs) have been found in virtually all body fluids and used successfully as biomarkers for various diseases. Evidence indicates that miRNAs have important roles in IgA nephropathy (IgAN), a major cause of renal failure. In this study, we looked for differentially expressed miRNAs in IgAN and further evaluated the correlations between candidate miRNAs and the severity of IgAN. Methods. Microarray and RT-qRCR (real-time quantitative polymerase chain reaction) were sequentially used to screen and further verify miRNA expression profiles in urinary sediments of IgAN patients in two independent cohorts. The screening cohort consisted of 32 urine samples from 18 patients with IgAN, 4 patients with MN (membranous nephropathy), 4 patients with MCD (minimal changes disease) and 6 healthy subjects; the validation cohort consisted of 102 IgAN patients, 41 MN patients, 27 MCD patients and 34 healthy subjects. The renal pathological lesions of patients with IgAN were evaluated according to Lee's grading system and Oxford classification. Results. At the screening phase, significance analysis of microarrays analysis showed that no miRNA was differentially expressed in the IgAN group compared to all control groups. But IgAN grade I-II and III subgroups (according to Lee's grading system) shared dysregulation of two miRNAs (miR-3613-3p and miR-4668-5p). At the validation phase, RT-qPCR results showed that urinary level of miR-3613-3p was significantly lower in IgAN than that in MN, MCD and healthy controls (0.47, 0.44 and 0.24 folds, respectively, all P < 0.01 by Mann-Whitney U test); urinary level of miR-4668-5p was also significantly lower in IgAN than that in healthy controls (0.49 fold, P < 0.01). Significant correlations were found between urinary levels of miR-3613-3p with 24-hour urinary protein excretion (Spearman r = 0.50, P = 0.034), eGFR (estimated glomerular filtration rate) (r = - 0.48, P = 0.043) and Lee's grades (r = 0.57, P = 0.014). Similarly, miR-4668-5p was significantly correlated with eGFR (r = - 0.50, P = 0.034) and Lee's grades (r = 0.57, P = 0.013). For segmental glomerulosclerosis according to Oxford classification, patients scored as S0 had significantly lower levels of urinary miR-3613-3p and miR-4668-5p than those scored as S1 (0.41 and 0.43 folds, respectively, all P < 0.05). Conclusions. The expression profile of miRNAs was significantly altered in urinary sediments from patients with IgAN. Urinary expression of miR-3613-3p was down-regulated in patients with IgAN. Moreover, urinary levels of both miR-3613-3p and miR-4668-5p were correlated with disease severity. Further studies are needed to explore the roles of miR-3613-3p and miR-4668-5p in the pathogenesis and progression of IgA nephropathy.

Dataset Information

Urinary prognostic biomarkers and classification of IgA nephropathy by high resolution mass spectrometry coupled with liquid chromatography.

Publications

Urinary prognostic biomarkers and classification of IgA nephropathy by high resolution mass spectrometry coupled with liquid chromatography.

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