Activated innate immunity and the involvement of CX3CR1–fractalkine in promoting hematuria in patients with IgA nephropathy

Cox, Sharon Natasha; Sallustio, Fabio; Serino, Grazia; Loverre, Antonia; Pesce, Francesco; Gigante, Margherita; Zaza, Gianluigi; Stifanelli, Patrizia; Ancona, Nicola; Schena, Francesco Paolo

doi:10.1038/ki.2012.147

Cited by 60 publications

(61 citation statements)

References 42 publications

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“…Recently, we reported that glomerular fraktalkine expression is involved in the pathogenesis and aggravation of childhood IgAN (Aizawa-Yashiro et al 2013;Tanaka and Imaizumi 2013). Furthermore, Cox et al (2012) have reported that increased glomerular expression of fraktalkine induces the onset of gross hematuria in adult patients with IgAN. However, the implications of both urinary fractalkine and MCP-1 concentrations in pediatric patients with GN remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Based on recent reports regarding the implications of expression of glomerular fractalkine in patients with IgAN (Cox et al 2012), fractalkine is thought to be a strong inducer of glomerular basement membrane (GBM) injury, resulting in massive hematuria. Thus, the urinary fractalkine concentration may be a predictor of inflammatory GBM damage in selected patients with GN.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it has been reported that measurement of urinary fractalkine levels is useful for monitoring of kidney transplant patients, since only changes in urinary fractalkine differentiate patients with acute rejection from those with acute tubular necrosis (Peng et al 2008). Furthermore, it has recently been reported that upregulation of glomerular and urinary expression of fractalkine promotes the onset of gross hematuria in adult patients with IgAN (Cox et al 2012). However, the implication of urinary fractalkine concent ration in children with GN remains to be determined.…”

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: 99%

Section: Discussionmentioning

confidence: 99%

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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“…Episodes of MH are frequently triggered by mucosal infections, mainly of the upper respiratory tract. Recently, Cox et al [19] found that patients with RMH exhibit an upregulated expression of the chemokine receptor CX3CR1 in their circulating leukocytes during episodes of MH; IgAN patients who have permanent microscopic hematuria are characterized by low glomerular fractalkine (CX3CR1 ligand) expression. On the other hand, IgAN patients characterized by RMH have an enhanced fractalkine expression in both podocytes and endothelial cells and an enhanced urinary level of this chemokine.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Outcome of IgA Nephropathy Patients with Recurrent Macroscopic Hematuria

Liang

Chen

et al. 2014

Am J Nephrol

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Background/Aims: The long-term renal outcomes of patients with IgA nephropathy (IgAN) who present with recurrent macroscopic hematuria (RMH) have not been described in previous studies. Methods: Patients with biopsy-proven primary IgAN in Jinling Hospital were divided into three groups according to different patterns of macroscopic hematuria (MH): RMH, isolated MH (IMH), and those without a history of MH (NMH). Results: A total of 1,155 patients were enrolled in the study (158 in the RMH group, 256 in the IMH group, and 741 in the NMH group). At biopsy, patients with RMH were younger, had lower median proteinuria, a lower incidence of hypertension, and a higher estimated glomerular filtration rate than those in the NMH group. Pathologically, patients with RMH had a lower level of mesangial hypercellularity and segmental glomerulosclerosis as well as less tubular atrophy than those with NMH. The demographic and clinical features of patients with IMH fell between patients with RMH and those with NMH. During a median follow-up of 7.9 years, the 5-, 10- and 20-year cumulative renal survival after biopsy, as calculated by K-M methods, were 98, 91, and 91% in the RMH group, 95, 89, and 64% in the IMH group, and 95, 79, and 57% in the NMH group. The renal survival in patients with RMH was significantly better than patients with NMH or IMH. Conclusions: The long-term prognosis of patients who present with RMH is significantly better than patients with NMH or IMH.

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“…Our recent experience on transcriptomics suggests that omics are available for creating specific classifiers in different diseases [19,20]. They are formed by a list of genes that are involved in the pathogenesis of the disease and they can be considered targeted genes for specific drugs [21].…”

Section: Expert Opinionmentioning

confidence: 99%

Biomarkers and personalized therapy in chronic kidney diseases

Schena

2014

Expert Opinion on Investigational Drugs

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Activated innate immunity and the involvement of CX3CR1–fractalkine in promoting hematuria in patients with IgA nephropathy

Cited by 60 publications

References 42 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

Long-Term Outcome of IgA Nephropathy Patients with Recurrent Macroscopic Hematuria

Biomarkers and personalized therapy in chronic kidney diseases

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