Urinary levels of epidermal growth factor, interleukin‐6 and monocyte chemoattractant protein‐1 may act as predictor markers of renal function outcome in immunoglobulin A nephropathy

Stangou, Maria; Alexopoulos, Efstathios; Papagianni, Αikaterini; Pantzaki, Afroditi; Bantis, Christos; Dovas, Spiros; Economidou, D.; Leontsini, Maria; Memmos, Dimitrios

doi:10.1111/j.1440-1797.2008.01051.x

Cited by 82 publications

(66 citation statements)

References 33 publications

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“…However, little information is available regarding the implication of urinary proinflammatory chemokine levels in pediatric-onset renal diseases (Watson et al 2012). So far, it has been reported that the urinary MCP-1 concentration may predict disease activity in adulthood IgAN and LN (Stangou et al 2009(Stangou et al , 2013Abujam et al 2013). Interestingly, Stangou et al (2009) have reported that the urinary MCP-1 concentration is significantly correlated with the degree of interstitial fibrosis, which is an index reflecting the histological chronicity, in adult patients with IgAN.…”

Section: Discussionmentioning

confidence: 97%

“…Alternatively, recent studies have reported the usefulness of determining the "stable" urinary protein levels of functional molecules in patients with glomerular diseases (Stangou et al 2009(Stangou et al , 2013Watson et al 2012;Abujam et al 2013;Korzeniecka-Kozerska et al 2013). Among such candidate urinary cytokines/chemokines, monocyte chemoattractant protein-1 (MCP-1) has been reported to be a possible biomarker reflecting glomerular inflammation in patients with LN and IgAN (Stangou et al 2009(Stangou et al , 2013Watson et al 2012;Abujam et al 2013), since glomerular expression of MCP-1 is actually involved in the pathogenesis and subsequent tissue injury (Marks et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Urinary Fractalkine and Monocyte Chemoattractant Protein-1 as Possible Predictors of Disease Activity of Childhood Glomerulonephritis

Aizawa¹,

Imaizumi

Tsuruga³

et al. 2013

Tohoku J. Exp. Med.

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Renal biopsy is the gold standard for confirmation of disease severity and diagnosis of glomerulonephritis (GN), but its procedure is invasive with a risk of complications. Thus, a non-invasive monitoring method is desirable especially in pediatric patients. Fractalkine and monocyte chemoattractant protein-1 (MCP-1) are proinflammatory chemokines, and both have been reported to be involved in the pathogenesis of immunocomplex-mediated GN. Recently, it has been reported that urinary fractalkine and MCP-1 may serve as possible predictors of disease activity of adult patients with GN. We, therefore, examined whether urinary levels of fractalkine and MCP-1 correlate with clinical and histologic parameters. Twenty-six consecutive children with various types of GN were enrolled in this study, including lupus nephritis, IgA nephropathy, membranous nephropathy, acute GN, and thin basement membrane disease (served as a non-inflammatory control). Urinary fractalkine and MCP-1 concentrations in the first morning urine samples obtained at the time of renal biopsy were measured by enzyme-linked immunosorbent assay, and standardized for urinary creatinine concentrations. Urinary fractalkine concentration differed significantly among the disease categories. Urinary concentrations of fractalkine and MCP-1 showed a significant positive correlation with the degree of occult blood in urine and a significant inverse correlation with the estimated glomerular filtration rate. Furthermore, the urinary MCP-1 concentration was significantly correlated with histological chronicity indices in patients with lupus nephritis and IgA nephropathy. Measurement of urinary fractalkine and MCP-1 concentrations may be useful as a non-invasive method for predicting the disease activity of GN in children.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Urinary Fractalkine and Monocyte Chemoattractant Protein-1 as Possible Predictors of Disease Activity of Childhood Glomerulonephritis

Aizawa¹,

Imaizumi

Tsuruga³

et al. 2013

Tohoku J. Exp. Med.

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“…In clinical studies of IgAN, patients with moderate to severe disease showed much higher renal MCP-1 mRNA and protein expression, and higher levels of urinary MCP-1, compared with patients with mild and nonprogressive disease. Urinary levels of IL-6 and IL-8 also correlate with histological lesions and levels of proteinuria (32)(33)(34). Furthermore, levels of renal gene expression of various cytokines and chemokines, including TNF-a, IL1b, IL-6, IL-8, and IFN-g, correlate with the pattern and extent of histological lesions and clinical findings (35).…”

Section: Discussionmentioning

confidence: 98%

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Kim

McDaid

McAdoo

et al. 2012

The Journal of Immunology

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IgA immune complexes are capable of inducing human mesangial cell (HMC) activation, resulting in release of proinflammatory and profibrogenic mediators. The subsequent inflammation, cellular proliferation, and synthesis of extracellular matrix lead to the progression of IgA nephropathy (IgAN). Spleen tyrosine kinase (SYK) is an intracellular protein tyrosine kinase involved in cell signaling downstream of immunoreceptors. In this study, we determined whether SYK is involved in the downstream signaling of IgA1 stimulation in HMC, leading to production of proinflammatory cytokines/chemokines and cell proliferation. Incubation of HMC with IgA1 purified from IgAN patients significantly increased the synthesis of MCP-1 in a dose-dependent manner. There was also significantly increased production of IL-6, IL-8, IFN-γ–inducible protein-10, RANTES, and platelet-derived growth factor-BB. Stimulation of HMC with heat-aggregated IgA1 purified from IgAN patients induced significantly increased HMC proliferation. Both pharmacological inhibition of SYK and knockdown of SYK by small interfering RNA significantly reduced the synthesis of these mediators and inhibited HMC proliferation. Moreover, positive immunostaining for total and phospho-SYK in glomeruli of kidney biopsies from IgAN patients strongly suggests the involvement of SYK in the pathogenesis of IgAN. To our knowledge, we demonstrate, for the first time, the involvement of SYK in the downstream signaling of IgA1 stimulation in HMC and in the pathogenesis of IgAN. Hence, SYK represents a potential therapeutic target for IgAN.

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“…Many studies have associated CCL2/MCP-1 with glomerulopathies [6,13,[19][20][21][22][23][24][25][26] and with renal transplantation [10,27,28]. Wada and coworkers found significantly elevated urinary levels of this chemokine in adults with diabetic nephropathy, whereas serum levels remained similar to those of healthy volunteers [21].…”

Section: Chemokines In Renal Diseasesmentioning

confidence: 99%

“…CCL2/MCP-1 was the first CC chemokine to be discovered, acting as a potent chemotactic factor for monocytes, and has been one of the most studied biomarkers [6,10,13,[17][18][19][20][21][22][23][24][25][26][27][28]. Many studies have associated CCL2/MCP-1 with glomerulopathies [6,13,[19][20][21][22][23][24][25][26] and with renal transplantation [10,27,28].…”

Section: Chemokines In Renal Diseasesmentioning

confidence: 99%

Chemokines as Potential Markers in Pediatric Renal Diseases

Silva¹,

Pereira²,

Teixeira³

et al. 2015

Biomarkers in Kidney Disease

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Glomerular diseases and obstructive uropathies are the two most frequent causes of chronic kidney disease (CKD) in children. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric renal diseases. Among several putative biomarkers, chemokines emerge as promising molecules since they play relevant roles in the pathophysiology of pediatric renal diseases. The evaluation of these inflammatory mediators might help in the management of diverse renal diseases in children and the detection of patients at high risk to develop CKD. The aim of this paper is to revise general aspects of chemokines and the potential link between chemokines and the most common pediatric renal diseases by including experimental and clinical evidence.

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Urinary levels of epidermal growth factor, interleukin‐6 and monocyte chemoattractant protein‐1 may act as predictor markers of renal function outcome in immunoglobulin A nephropathy

Abstract: Urinary MCP-1, IL-6 and EGF levels may represent histology in IgAN. EGF excretion can be a predictive marker and its serial measurements may give information about disease outcome and the effect of treatment.

Cited by 82 publications

References 33 publications

Urinary Fractalkine and Monocyte Chemoattractant Protein-1 as Possible Predictors of Disease Activity of Childhood Glomerulonephritis

Urinary Fractalkine and Monocyte Chemoattractant Protein-1 as Possible Predictors of Disease Activity of Childhood Glomerulonephritis

Spleen Tyrosine Kinase Is Important in the Production of Proinflammatory Cytokines and Cell Proliferation in Human Mesangial Cells following Stimulation with IgA1 Isolated from IgA Nephropathy Patients

Chemokines as Potential Markers in Pediatric Renal Diseases

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