Proteinuria is often used as a surrogate marker in monitoring and predicting outcome in patients with chronic kidney diseases, but it is non-specific. IgAN belongs to the most common primary glomerulonephritis worldwide with serious prognosis. The main aim of this work was to assess differences in urine proteins in patients with IgA nephropathy and to identify abnormal proteins as potential biomarkers of IgA nephropathy or the renal disease. In our pilot project, we selected 20 patients and compared them with 20 healthy volunteers. Protein quantification was performed using iTRAQ (isobaric tag for relative and absolute quantitation) labeling method. The peptides were separated by the isoelectric focusing method (IEF) and nano-LC with C18 column and identified by mass spectrometry using MALDI-TOF/TOF MS. Proteins´ lists obtained from IEF-LC-MS-MS/MS analysis were combined and contained 201 proteins. It was found out that 113 proteins were common in both experiments. 30 urinary proteins were significantly up- or down-regulated in patients with IgA nephropathy. We characterized potential biomarkers such as alpha-1-antitrypsin, apolipoprotein A-I, CD44 antigen or kininogen. Potential biomarkers of IgAN should be validated in further studies.
- MeSH
- alfa-1-antitrypsin genetika moč MeSH
- apolipoprotein A-I genetika moč MeSH
- biologické markery moč MeSH
- dospělí MeSH
- IgA nefropatie diagnóza genetika moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- pilotní projekty MeSH
- proteomika metody MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ANCA-asociované vaskulitidy * imunologie moč MeSH
- autoprotilátky moč MeSH
- biologické markery moč MeSH
- IgA nefropatie * imunologie moč MeSH
- komplement C1q imunologie moč MeSH
- lidé MeSH
- membranózní glomerulonefritida * imunologie moč MeSH
- nefritida při lupus erythematodes * imunologie moč MeSH
- protilátky proti cytoplazmě neutrofilů moč MeSH
- receptory pro fosfolipasy A2 imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl(4), and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria.
- MeSH
- časové faktory MeSH
- desmin genetika metabolismus MeSH
- fluorescenční protilátková technika MeSH
- hematurie metabolismus MeSH
- IgA nefropatie chemicky indukované metabolismus patologie moč MeSH
- intracelulární signální peptidy a proteiny genetika metabolismus MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- membránové proteiny genetika metabolismus MeSH
- messenger RNA metabolismus MeSH
- modely nemocí na zvířatech MeSH
- podocyty metabolismus ultrastruktura MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- potkani Sprague-Dawley MeSH
- progrese nemoci MeSH
- proteinurie chemicky indukované metabolismus patologie moč MeSH
- transmisní elektronová mikroskopie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with <1 g/d of sustained proteinuria, the rate of decline was 90% slower than the mean rate. The rate of decline increased with the amount of proteinuria, such that those with sustained proteinuria >3 g/d (n = 121) lost renal function 25-fold faster than those with <1 g/d. Patients who presented with > or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.
- MeSH
- dospělí MeSH
- hodnoty glomerulární filtrace MeSH
- IgA nefropatie diagnóza moč terapie MeSH
- indukce remise MeSH
- ledviny patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- multivariační analýza MeSH
- prognóza MeSH
- proteinurie terapie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- dietní proteiny MeSH
- dospělí MeSH
- glomerulus MeSH
- IgA nefropatie moč MeSH
- lidé MeSH
- proteinurie diagnóza etiologie MeSH
- sporty MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- kongresy MeSH
- Klíčová slova
- EPA (WALMARK),
- MeSH
- dospělí MeSH
- IgA nefropatie farmakoterapie moč MeSH
- ikosanoidy moč MeSH
- lidé MeSH
- rybí oleje aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kongresy MeSH
- srovnávací studie MeSH