Absence of Increased α1-Microglobulin in IgA Nephropathy Proteinuria

Hiramoto, Masashi; Okada, Hirokazu; Kanno, Yoshihiko; Yuri, Masatoshi; Morita, Shigeaki; Naitou, Masanori; Ichikawa, Atsushi; Katoh, Miyuki; Suzuki, Hiromichi

doi:10.1074/mcp.m600336-mcp200

Cited by 31 publications

(21 citation statements)

References 16 publications

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“…Similar to reports that observed A1AT protein or its fragments [4,15,17,18,19,21,22], we identified three peptides – potentially derived from A1AT cleavage from its C-terminus during protease inhibition and elevated in GKD patients. Although examining urinary peptides by immunoassay is difficult, e.g.…”

Section: Discussionsupporting

confidence: 69%

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Uromodulin and α<sub>1</sub>-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

Navarro-Muñoz

Ibernón

Bonet

et al. 2012

Kidney Blood Press Res

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Background/Aims: Glomerular kidney disease (GKD) is suspected in patients based on proteinuria, but its diagnosis relies primarily on renal biopsy. We used urine peptide profiling as a noninvasive means to link GKD-associated changes to each glomerular entity. Methods: Urinary peptide profiles of 60 biopsy-proven glomerular patients and 14 controls were analyzed by combining magnetic bead peptide enrichment, MALDI-TOF MS analysis, and ClinProTools v2.0 to select differential peptides. Tentative identification of the differential peptides was carried out by HPLC-MS/MS. Results: The HPLC-MS/MS results suggest that uromodulin (UMOD; m/z: 1682, 1898 and 1913) and α₁-antitrypsin (A1AT; m/z: 1945, 2392 and 2505) are differentially expressed urinary peptides that distinguish between GKD patients and healthy subjects. Low UMOD and high A1AT peptide abundance was observed in 80–92% of patients with GKD. Proliferative forms of GKD were distinguished from nonproliferative forms, based on a combination of UMOD and A1AT peptides. Nonproliferative forms correlated with higher A1AT peptide levels – focal segmental glomerulosclerosis was linked more closely to high levels of the m/z 1945 peptide than minimal change disease. Conclusion: We describe a workflow – urinary peptide profiling coupled with histological findings – that can be used to distinguish GKD accurately and noninvasively, particularly its nonproliferative forms.

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Section: Discussionsupporting

confidence: 69%

“…Urine is one of the most amenable fluids in clinical proteomics, because it can be obtained noninvasively, allowing one to identify GKD-related markers [12,13,14,15,16,17,18,19,20,21,22]. Profiling methods are gaining popularity in the quest for new putative biomarkers for glomerular disorders [23,24,25,26,27,28,29,30,31].…”

Section: Introductionmentioning

confidence: 99%

Uromodulin and α<sub>1</sub>-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

Navarro-Muñoz

Ibernón

Bonet

et al. 2012

Kidney Blood Press Res

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“…For proteomic analysis, urine samples were first centrifuged at 1500 × g for 10 min at 4°C to remove debris. The supernatants were concentrated and desalted to remove interfering substances by centrifugation at 7500 × g for 30 min at 4°C using a centrifugal filter device (Amicon Ultra 4 molecular mass cutoff, 10-kDa; Merck Millipore, Billerica, MA, USA) as previously described [58]. The desalted concentrates were stored at −20°C until further use.…”

Section: Methodsmentioning

confidence: 99%

Identification of leptospiral 3-hydroxyacyl-CoA dehydrogenase released in the urine of infected hamsters

et al. 2014

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BackgroundLeptospirosis is a global zoonosis caused by pathogenic Leptospira. The non-specific clinical signs and symptoms of leptospirosis lead to its misdiagnosis. To date, there is still no reliable rapid test kit that can accurately diagnose leptospirosis at bedside or in field. In this research, with the ultimate goal of formulating a rapid and accurate diagnostic tool for leptospirosis, we aimed to identify leptospiral proteins excreted in urine of infected hamsters, which are thought to mimic Weil’s disease.ResultsHamsters were subcutaneously infected with leptospires, and the general attributes of urine as well as the proteins excreted in it were examined. Some leptospiral proteins were found to be excreted in the urine from the early phase of infection. The most important finding of this study was the detection of the lipid-metabolizing enzyme, 3-hydroxyacyl-CoA dehydrogenase (HADH), before the onset of illness, when leptospires were not yet detected in the urine of infected hamsters.ConclusionsThis is the first report on the detection of leptospiral HADH in the host urine, which may be a possible candidate leptospiral antigen that can be used in the early diagnosis of human and animal leptospirosis.

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“…Yokota et al [25] analyzed with 2D-DIGE and MS the urinary pattern of 17 IgAN patients, 10 healthy controls and 16 patients with diabetic nephropathy (DN). Most of 174 spots identified in urine were degradation products of albumin and serum proteins and their amounts in IgAN were higher than in normal controls; only 1-microglobulin was not higher in IgAN patients than in normal controls; these data were confirmed by ELISA.…”

Section: Ability Of Igan Specific Biomarkers Assessed By Ce-ms To Dmentioning

confidence: 99%

IgA Nephropathy: Clinical Significance of Urinary Proteins/Polypeptides Characterization

Bazzi¹

2009

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IgA nephropathy (IgAN), the most frequent type of glomerulonephritis, is characterized at biopsy by a wide variability of functional, proteinuric and histologic features; about 30% of patients progress to end stage renal disease (ESRD). Baseline proteinuria is one of the main predictors of progression. Few studies evaluated whether some components of proteinuria improve prediction of the outcome and may identify patients for whom different therapeutic approaches are indicated (no treatment, renin-angiotensin system (RAS) inhibition, immunosuppression). The composition of proteinuria was assessed by classical methods (SDS-PAGE, immunonephelometry); recently new technologies [mainly capillary electrophoresis coupled to mass spectrometry (CE-MS)] were able to analyze the whole spectrum of urinary proteins/polypeptides. Low molecular weight proteins in SDS-PAGE pattern predicted progression. Urinary excretion of IgG, a reliable marker of selectivity of glomerular capillary wall, predicted progression better than proteinuria/day and other markers by univariate and multivariate analysis. Fractional Excretion of IgG identified patients responsive to ACEinhibitors (ACEi) in non-crescentic IgAN and patients responsive to immunosuppression in crescentic-IgAN. CE-MS identified a specific "IgAN polypeptide pattern" significantly different from controls and from other glomerular diseases with high sensitivity and specificity. In patients treated with ACEi the analysis with 2-D PAGE coupled to nano-HPLC-ESI-MS/MS identified 3 proteins [kininogen, inter--trypsin inhibitor heavy chain H4 and transthyretin] whose excretion was significantly different in ACEi-responders vs non-responders. Baseline low kininogen excretion predicted inadeguate/absent response to ACEi. Conclusions: urinary excretion of IgG is to date the best proteinuric predictor of progression and responsiveness to ACEi in non-crescentic IgAN and to immunosuppression in crescentic IgAN . Urinary profile assessed by proteome analysis identifies a polypeptide pattern that distinguishes IgAN from healthy controls and other glomerular diseases and some proteins whose value predicts ACEi-responsiveness. Future developments of urinary proteome characterization in larger cohorts of patients may further improve diagnosis, prognostication and therapeutic approach.

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Absence of Increased α1-Microglobulin in IgA Nephropathy Proteinuria

Cited by 31 publications

References 16 publications

Uromodulin and α<sub>1</sub>-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

Uromodulin and α<sub>1</sub>-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

Identification of leptospiral 3-hydroxyacyl-CoA dehydrogenase released in the urine of infected hamsters

IgA Nephropathy: Clinical Significance of Urinary Proteins/Polypeptides Characterization

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