Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes

Christiansen, Merete Skovdal; Iversen, Kasper; Larsen, Casper; Goetze, Jens P.; Hommel, Eva; Mølvig, Jens; Pedersen, Bente Klarlund; Magid, Erik; Feldt‐Rasmussen, Bo

doi:10.1080/00365510802531100

Cited by 23 publications

(18 citation statements)

References 48 publications

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“…Orosomucoid, α-1 acid glycoprotein with 41 kDa, is an acute-phase protein and the serum concentrations correlated with low-grade inflammation in the patients with diabetes [28], [29]. Urine excretion of orosomucoid was increased in the patients with diabetes and normoalbuminuria and it correlated with markers of inflammation such as CRP [29]–[31] and markers for endothelial dysfunction [32]. Type 2 diabetic patients with elevated urinary orosomucoid excretion exhibited normal glomerular and tubular function, suggesting the possibility of local renal production of orosomucoid due to chronic low-grade inflammation rather than hyperfiltration [33].…”

Section: Discussionmentioning

confidence: 97%

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

et al. 2013

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We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Siaα2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography–tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40±0.43; A2, 0.60±0.53; A3 1.57±1.13 ng/gCr; p = 7.29×10−8) and of GFR stages (G1, 0.39±0.39; G2, 0.49±0.45; G3, 1.25±1.18; G4, 1.34±0.80 ng/gCr; p = 3.89×10−4). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881–11.844) and 3.739 (1.785–7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 97%

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

et al. 2013

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“…In spite of the fact that the elevation of urinary orosomucoid (u-ORM) concentrations seems to be a non-specific marker, several publications stated that u-ORM might serve advantageous information on early monitoring of certain inflammatory disorders. Elevated u-ORM was described in diabetes mellitus associated with the ongoing chronic low-grade inflammation and endothelial dysfunction and was considered to be an independent predictor of diabetic nephropathy and cardiovascular mortality among patients with type 2 diabetes ( 15 - 19 ). Recent findings suggest that it also might be a potential novel marker for the early detection of chronic heart failure ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Urinary orosomucoid: validation of an automated immune turbidimetric test and its possible clinical use

et al. 2016

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IntroductionBesides routine serum markers of inflammatory diseases, the diagnostic potential of selected urinary proteins has not been fully exploited yet. Former studies revealed that urinary orosomucoid (u-ORM) might have complementary information in inflammatory disorders. Our aim was to develop and validate a fully automated method for u-ORM measurements and to evaluate its potential clinical impact on systemic inflammatory diseases.Materials and methodsA particle-enhanced immune turbidimetric assay was validated for a Cobas 8000/c502 analyzer to determine u-ORM levels. Spot urine samples from 72 healthy individuals, 28 patients with Crohn’s disease and 30 septic patients were studied.ResultsOur assay time was 10 minutes and the detection limit of u-ORM was 0.02 mg/L. The intra- and inter-assay imprecision expressed as CV was less than 5%, and the recovery ranged between 95–103%. Within 10 to 60 years of age, a preliminary reference range for urinary orosomucoid/creatinine ratio (u-ORM/u-CREAT) was found to be 0.08 (0.01–0.24) mg/mmol [median (2.5–97.5 percentiles)]. Compared to controls, a five-fold increase of u-ORM/u-CREAT values in Crohn’s disease and approximately a 240-fold increase in sepsis were observed.ConclusionsWe set up a fast, sensitive and precise turbidimetric approach for automated u-ORM determination. Our highly sensitive assay is ideal for routine u-ORM measurements and might be a potential novel laboratory test in the management of systemic inflammatory processes.

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“…This protein is known as an acute-phase protein that has immunomodulatory as well as anti-inflammatory effect and is also a marker for inflammatory diseases and endothelial injury [59–61]. Increased urinary alpha-1-acid glycoprotein has been reported to be associated with kidney injury caused by radiation therapy, trauma, and type II diabetes [62].…”

Section: Discussionmentioning

confidence: 99%

The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis

Nafar

Kalantari

Samavat

et al. 2014

International Journal of Nephrology

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Background. Focal segmental glomerulosclerosis (FSGS) is a glomerular injury with various pathogenic mechanisms. Urine proteome panel might help in noninvasive diagnosis and better understanding of pathogenesis of FSGS. Method. We have analyzed the urine sample of 11 biopsy-proven FSGS subjects, 8 healthy controls, and 6 patients with biopsy-proven IgA nephropathy (disease controls) by means of liquid chromatography tandem mass spectrometry (nLC-MS/MS). Multivariate analysis of quantified proteins was performed by principal component analysis (PCA) and partial least squares (PLS). Results. Of the total number of 389 proteins, after multivariate analysis and additional filter criterion and comparing FSGS versus IgA nephropathy and healthy subjects, 77 proteins were considered as putative biomarkers of FSGS. CD59, CD44, IBP7, Robo4, and DPEP1 were the most significant differentially expressed proteins. These proteins are involved in pathogenic pathways: complement pathway, sclerosis, cell proliferation, actin cytoskeleton remodeling, and activity of TRPC6.There was complete absence of DPEP1 in urine proteome of FSGS subjects compared with healthy and disease controls. DPEP1 acts via leukotrienes on TRPC6 and results in increased podocyte motility and proteinuria. Conclusion. The results suggest a panel of candidate biomarkers for noninvasive diagnosis of FSGS, while complete absence of DPEP1 might represent a novel marker of FSGS.

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Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes

Cited by 23 publications

References 48 publications

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray

Urinary orosomucoid: validation of an automated immune turbidimetric test and its possible clinical use

The Novel Diagnostic Biomarkers for Focal Segmental Glomerulosclerosis

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