Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy

2018 ◽  
Vol 34 (9) ◽  
pp. 1549-1558 ◽  
Author(s):  
Ran Luo ◽  
Shui-Ming Guo ◽  
Yue-Qiang Li ◽  
Yi Yang ◽  
Meng-Lan Li ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Creatinine Level ◽  
Mesangial Cells ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Chinese Patients ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Urine Protein ◽  
Mesangial Hypercellularity

Abstract Background A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients. Methods Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed. Results The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7. Conclusions Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN.

Podocytopathy in the mesangial proliferative immunoglobulin A nephropathy: new insights into the mechanisms of damage and progression

2019 ◽  
Vol 34 (8) ◽  
pp. 1280-1285 ◽  
Author(s):  
Hernán Trimarchi ◽  
Rosanna Coppo
Keyword(s):  
Mesangial Cells ◽  
Immunosuppressive Treatment ◽  
Immunoglobulin A ◽  
Primary Site ◽  
New Drugs ◽  
Immunoglobulin A Nephropathy ◽  
Inflammatory Reactions ◽  
Persistent Proteinuria ◽  
Mesangial Area ◽  
Function Loss

Abstract Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition of IgA immune material is the mesangium, and proliferation of mesangial cells and matrix excess deposition are the first histopathologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuria, and recent studies indicate that a major role is played by previous damage of function and anatomy of podocytes. In IgAN, the podocytopathic changes are the consequence of initial alterations in the mesangial area with accumulation of IgA containing immune material. Podocytes are therefore affected by interactions of messages originally driven from the mesangium. After continuous insult, podocytes detach from the glomerular basement membrane. This podocytopathy favours not only the development of glomerular focal and segmental sclerosis, but also the progressive renal function loss. It is still debated whether these lesions can be prevented or cured by corticosteroid/immunosuppressive treatment. We aimed to review recent data on the mechanisms implicated in the podocytopathy present in IgAN, showing new molecular risk factors for progression of this disease. Moreover, these observations may indicate that the target for new drugs is not only focused on decreasing the activity of mesangial cells and inflammatory reactions in IgAN, but also on improving podocyte function and survival.

scholarly journals Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Coagulation System ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Tubular Atrophy ◽  
Coagulation Parameters ◽  
T Score ◽  
Stage Renal Disease

Abstract Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods: This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s). Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

Expression of response gene to complement-32 in renal tissue of children with immunoglobulin A nephropathy

2011 ◽  
Vol 45 (5) ◽  
pp. 371-376 ◽  
Author(s):  
Xiao-Ling Niu ◽  
Xin-Yu Kuang ◽  
Zhi-Gang Zhang ◽  
Xue-Guang Liu ◽  
Zhong-Hua Zhao ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Renal Tissue ◽  
Immunoglobulin A Nephropathy ◽  
Response Gene

Detection of α1 Integrin in Urine of Patients With Immunoglobulin A Nephropathy

2008 ◽  
Vol 56 (3) ◽  
pp. 581-586
Author(s):  
Jonathan Bank ◽  
Aharon Ben-David ◽  
Ram Doolman ◽  
Ben-Ami Sela ◽  
Ilan Bank
Keyword(s):  
Mesangial Cells ◽  
Kidney Diseases ◽  
Surface Membrane ◽  
Immunoglobulin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Healthy Individuals ◽  
Immunoglobulin A Nephropathy ◽  
A Cell ◽  
Dose Dependent

BackgroundThe α1β1 integrin is a cell surface membrane heterodimer composed of noncovalently linked α1 and β1 polypeptides that is up-regulated on activated and proliferating mesangial cells.MethodsA double-sandwich enzyme-linked immunosorbent assay that detects α1 integrin in a specific and dose-dependent manner at concentrations greater than 150 ng/mL was used to evaluate whether intact α1 polypeptides are secreted in the urine samples of 29 patients with various kidney diseases and in those of 5 healthy individuals.Resultsα1 Integrin was detected in 8 of the 29 patients including 3 of 3 patients with biopsy-proven immunoglobulin A nephropathy and 3 of 3 clinically suspected but non-biopsy-proven immunoglobulin A nephropathy with evidence of active nephritis. No α1 integrins were found in samples of 5 healthy controls.Conclusionsα1 Integrin polypeptides can be detected in human urine, particularly in immunoglobulin A nephropathy. Further extensive studies are required to clarify the significance of secretion of α1 integrins in urine of patients with kidney disease.

scholarly journals Salivary microbial analysis of Chinese patients with immunoglobulin�A nephropathy

2019 ◽  
Author(s):  
Shaodong Luan ◽  
Shuyuan Zhang ◽  
Huanli Zhong ◽  
Yingwei Zhang ◽  
Xing Wei ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Chinese Patients ◽  
Immunoglobulin A Nephropathy ◽  
Microbial Analysis

scholarly journals The Urinary Exosomal miRNA Expression Profile is Predictive of Clinical Response in Lupus Nephritis

2020 ◽  
Vol 21 (4) ◽  
pp. 1372 ◽  
Author(s):  
Eloi Garcia-Vives ◽  
Cristina Solé ◽  
Teresa Moliné ◽  
Marta Vidal ◽  
Irene Agraz ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Clinical Response ◽  
Mesangial Cells ◽  
Area Under The Curve ◽  
Mirna Expression Profile ◽  
Renal Tissue ◽  
Renal Outcome ◽  
Protein Levels ◽  
Urinary Exosomes

Data on exosomal-derived urinary miRNAs have identified several miRNAs associated with disease activity and fibrosis formation, but studies on prognosis are lacking. We conducted a qPCR array screening on urinary exosomes from 14 patients with biopsy-proven proliferative lupus glomerulonephritis with a renal outcome of clinical response (n = 7) and non-response (n = 7) following therapy. Validation studies were performed by qRT-PCR in a new lupus nephritis (LN) cohort (responders = 22 and non-responders = 21). Responder patients expressed significantly increased levels of miR-31, miR-107, and miR-135b-5p in urine and renal tissue compared to non-responders. MiR-135b exhibited the best predictive value to discriminate responder patients (area under the curve = 0.783). In vitro studies showed exosome-derived miR-31, miR-107, and miR-135b-5p expression to be mainly produced by tubular renal cells stimulated with inflammatory cytokines (e.g IL1, TNFα, IFNα and IL6). Uptake of urinary exosomes from responders by mesangial cells was superior compared to that from non-responders (90% vs. 50%, p < 0.0001). HIF1A was identified as a potential common target, and low protein levels were found in non-responder renal biopsies. HIF1A inhibition reduced mesangial proliferation and IL-8, CCL2, CCL3, and CXCL1 mesangial cell production and IL-6/VCAM-1 in endothelial cells. Urinary exosomal miR-135b-5p, miR-107, and miR-31 are promising novel markers for clinical outcomes, regulating LN renal recovery by HIF1A inhibition.

Molecular Analysis of C3 Allotypes in Chinese Patients With Immunoglobulin A Nephropathy

1994 ◽  
Vol 23 (4) ◽  
pp. 543-546 ◽  
Author(s):  
Jacqueline E. Finn ◽  
Philip K.T. Li ◽  
Kar Neng Lai ◽  
Peter W. Mathieson
Keyword(s):  
Molecular Analysis ◽  
Immunoglobulin A ◽  
Chinese Patients ◽  
Immunoglobulin A Nephropathy

scholarly journals The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy

2021 ◽  
Author(s):  
Francesco Paolo Schena ◽  
Michele Rossini ◽  
Daniela Isabel Abbrescia ◽  
Gianluigi Zaza
Keyword(s):  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Kidney Biopsy ◽  
Immunoglobulin A ◽  
Renal Tissue ◽  
Urinary Biomarkers ◽  
Specific Gene ◽  
Rna Seq ◽  
Immunoglobulin A Nephropathy ◽  
Renal Lesions

AbstractKidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions. Over the past three decades, renal transcriptomic studies have been performed on fresh or frozen renal tissue, and formalin-fixed paraffin-embedded kidney tissue specimens obtained from archival histological repositories. This paper aims to describe (1) the transcriptomic profiles of the kidney biopsy and (2) the potential urinary biomarkers that can be used to monitor the follow-up of IgAN patients. The use of quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), microarrays and RNA-sequencing (RNA-seq) techniques on renal tissue and separated compartments of the nephron such as glomeruli and tubule-interstitium has clarified many aspects of the renal damage in IgAN. Recently, the introduction of the single-cell RNA-seq techniques has overcome the limitations of the previous methods, making that it is possible to study the whole renal tissue without the dissection of the nephron segments; it also allows better analysis of the cell-specific gene expression involved in cell differentiation. These gene products could represent effective candidates for urinary biomarkers for clinical decision making. Finally, some of these molecules may be the targets of old drugs, such as corticosteroids, renin–angiotensin–aldosterone blockers, and new drugs such as monoclonal antibodies. In the era of personalized medicine and precision therapy, high-throughput technologies may better characterize different renal patterns of IgAN and deliver targeted treatments to individual patients.

scholarly journals The association of microhematuria with mesangial hypercellularity, endocapillary hypercellularity, crescent score and renal outcomes in immunoglobulin A nephropathy

2019 ◽  
Author(s):  
Shane A Bobart ◽  
Mariam P Alexander ◽  
Khaled Shawwa ◽  
Lisa E Vaughan ◽  
Ranine Ghamrawi ◽  
...  
Keyword(s):  
Estimated Glomerular Filtration Rate ◽  
Independent Predictor ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy ◽  
High Power Field ◽  
Surrogate Outcome ◽  
Mesangial Hypercellularity ◽  
Egfr Decline ◽  
Endocapillary Hypercellularity

Abstract Background Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores. Methods In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf). Results Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P &lt; 0.05 for all) compared with patients without microhematuria. Of the 125 patients, 72 had follow-up data available. An increase in the degree of microhematuria was significantly associated with an eGFR decline of −0.81 mL/min/1.73 m2 [95% confidence interval (CI) −1.44 to −0.19, P = 0.01], after adjusting for follow-up time, proteinuria and T score. Severe microhematuria (≥21 RBCs/hpf) was associated with an even larger decline in eGFR (−3.99 mL/min/1.73 m2; 95% CI −6.9411 to −1.0552, P = 0.008), after similar adjustments. Conclusion Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.

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