Biomarkers in IGA Nephropathy

Hwang, Vicki J.; Ulu, Arzu; Hoorebeke, Justin van; Weiss, Robert H.

doi:10.2217/bmm.14.92

Cited by 7 publications

(6 citation statements)

References 80 publications

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“…However, because renal biopsy is an invasive diagnostic method and cannot be performed periodically, there are limitations to validating treatment outcomes and predicting the prognoses. Moreover, there is a growing interest in identification of biomarkers as a method to complement the limitations of renal biopsy 5 .…”

Section: Introductionmentioning

confidence: 99%

IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

Cho

Park

et al. 2019

Sci Rep

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Mitochondrial injury plays important roles in the pathogenesis of various kidney diseases. However, mitochondrial injury in IgA nephropathy (IgAN) remains largely unexplored. Here, we examined the associations among mitochondrial injury, IgAN, and treatment outcomes. We prospectively enrolled patients with IgAN and age-/sex-matched healthy volunteers (HVs) as controls (n = 31 each). Urinary copy numbers of the mitochondrial DNA (mtDNA) genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured. Urinary mtDNA levels were elevated in the IgAN group compared with that in HVs (p < 0.001). Urinary ND1 levels were significantly higher in the low proteinuria group than in the high proteinuria group (p = 0.027). Changes in urinary levels of ND1 and COX3 were positively correlated with changes in proteinuria (p = 0.038 and 0.024, respectively) and inversely correlated with changes in the estimated glomerular filtration rate (p = 0.033 and 0.017, respectively) after medical treatment. Mitochondrial injury played important roles in IgAN pathogenesis and may be involved in early-stage glomerular inflammation, prior to pathological changes and increased proteinuria. The correlation between changes in urinary mtDNA and proteinuria suggest that these factors may be promising biomarkers for treatment outcomes in IgAN.

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Section: Introductionmentioning

confidence: 99%

IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

Cho

Park

et al. 2019

Sci Rep

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“…Moreover, urinary peptidomics approaches have been utilized to develop non-invasive diagnostic tools based on a panel of differentially expressed molecules, able to differentiate IgAN from patients with other glomerular diseases 27 . None of the aforementioned markers has been implemented in clinical settings until now, stressing the unmet need for novel biomarkers, able to successfully diagnose early stages of the disease 28 .…”

Section: Introductionmentioning

confidence: 99%

Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis

Krochmal

Cisek

Filip

et al. 2017

Sci Rep

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IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming at identification of novel molecular signatures of the disease. Nine published urinary proteomics datasets were collected and the reported differentially expressed proteins in IgAN vs. healthy controls were integrated into known biological pathways. Proteins participating in these pathways were subjected to multi-step assessment, including investigation of IgAN transcriptomics datasets (Nephroseq database), their reported protein-protein interactions (STRING database), kidney tissue expression (Human Protein Atlas) and literature mining. Through this process, from an initial dataset of 232 proteins significantly associated with IgAN, 20 pathways were predicted, yielding 657 proteins for further analysis. Step-wise evaluation highlighted 20 proteins of possibly high relevance to IgAN and/or kidney disease. Experimental validation of 3 predicted relevant proteins, adenylyl cyclase-associated protein 1 (CAP1), SHC-transforming protein 1 (SHC1) and prolylcarboxypeptidase (PRCP) was performed by immunostaining of human kidney sections. Collectively, this study presents an integrative procedure for -omics data exploitation, giving rise to biologically relevant results.

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“…Moreover, Gd-IgA1 are increased in patients, but also in healthy relatives [20]. In conclusion, high levels of Gd-IgA1 are necessary for the development of IgAN, but not sufficient for the full clinical expression of the renal damage, and in most reports this biomarker is not associated with signs of progressive disease with proteinuria and glomerular filtration rate (GFR) decline [10,11,15]. However, higher levels of Gd-IgA1 are present in a subset of IgAN with severe clinical and renal features and predict a poor prognosis, and in recurrent IgAN after transplantation [21].…”

Section: Biomarkers Specific To Iganmentioning

confidence: 99%

“…The proteomic investigation in biofluids of patients with IgAN has detected several biomarkers of inflammation and progression, most of them belonging to the complement and coagulation pathways [11,41]. Several old and new data have indicated the role of complement dysregulation in IgAN, as complement factor deposits in association with IgA, particularly C5b-9, mannose binding lectin, ficolin, and C4b, indicating the prevalence of the lectin pathway activation [41][42][43].…”

Section: Complement As Biomarkers For Igan and Therapeutic Approachesmentioning

confidence: 99%

“…However, renal biopsy is needed in these subjects, not only for a correct diagnosis, but for detecting histological biomarkers of progression [4,6], as discussed below. The interest in biomarkers in IgAN is demonstrated by more than 800 publications in PubMed (reviewed in Hastings et al, Hwang et al, and Moresco et al [10][11][12]). The list is almost endless, as some of them have common factors with other glomerular diseases or chronic nonrenal diseases, and it is outside of the intent of this report to list all of them.…”

Section: Introductionmentioning

confidence: 99%

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Biomarkers and targeted new therapies for IgA nephropathy

Coppo

2016

Pediatr Nephrol

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IgA nephropathy (IgAN) has variable clinical presentation and outcome. There is a need to identify children who have the potential to progress to end stage renal disease (ESRD). Biomarkers related to the pathogenetic process of IgAN can detect risk factors and identify targets for new therapies. Galactose-deficient IgA1 (Gd-IgA1) is a specific biomarker of IgAN and could be the first treatment target. In experimental mice, reduction of IgA1 deposits and hematuria was observed after treatment with a bacterial protease that selectively cleaves human IgA1. Glycan-targeted drugs that may act to neutralize Gd-IgA1 inhibit abnormal enzymatic glycosylation of IgA1 or deplete cells producing Gd-IgA1. The autoimmune response to Gd-IgA1 produces autoantibodies that are sensitive and specific biomarkers of IgAN development and progression and suggests the possible benefits of anti-B cell therapies directed against CD20, B-cell activating factor (BAFF), or B cell receptor, and also proteasome inhibitors. The activation of complement in IgAN offers new biomarkers and the rationale for using complement inhibitors, including eculizumab. Renal pathological features represent sensitive biomarkers of added value over clinical data and may drive steroid therapy in selected cases. Finally, the hypothesis of the involvement of intestinal mucosal immunity in the pathogenesis of IgAN suggests the possibility of avoiding the systemic effect of steroid. Enteric budesonide targeting Peyer's patches at the ileocecal junction is an interesting option that has provided some preliminary favorable results in IgAN. In conclusion, the identification of new biomarkers is a promising area for therapies targeting IgAN in patients at risk of progression.

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Biomarkers in IGA Nephropathy

Cited by 7 publications

References 80 publications

IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

IgA nephropathy is associated with elevated urinary mitochondrial DNA copy numbers

Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis

Biomarkers and targeted new therapies for IgA nephropathy

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