Omics are Getting Us Closer to Understanding IgA Nephropathy

Mucha, Krzysztof; Pac, Michał; Pączek, Leszek

doi:10.1007/s00005-023-00677-w

Cited by 5 publications

(2 citation statements)

References 114 publications

(155 reference statements)

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“…Besides, previous studies shown the association of IgAN with genetic variations in the HLA gene family, as well as other genes like TAP1/PSMB and DEFA across diverse populations. These genetic factors may contribute to the pathogenesis of IgAN and its complications, including TMA (36)(37)(38). Still, endothelial damage induced by C5b-9 leads to increased expression of the von Willebrand factor gene, promoting platelet activation and the formation of thrombi (26).…”

Section: Genetics Of Tma In Iganmentioning

confidence: 99%

Thrombotic microangiopathy in IgA nephropathy: pathophysiology, histopathology, and treatment perspectives

Rastegar-Kashkouli,

Jafari,

Shahrokh

et al. 2024

J Nephropathol

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The current narrative review study aims to provide an overview of thrombotic microangiopathy (TMA) in immunoglobulin A nephropathy (IgAN), with a particular emphasis on its pathophysiology, histopathology, and treatment options. The prevalence and clinical significance of TMA in IgAN may vary across different populations. Estimates suggest that TMA events occur in 2-50% of patients with IgAN. Endothelial injury is a key factor in TMA development in IgAN, triggered by immune complex deposition, complement activation, and potentially hypertension. TMA in IgAN correlates with vascular lesions, including arterial intimal sclerosis, arteriolar lumen reduction, and smooth muscle hypertrophy. Notably, patients with TMA show more intense deposition of C4, C3d, and C5b-9 complements. Treatment involves blood pressure management, immunosuppression, and targeted therapies such as eculizumab.

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Section: Genetics Of Tma In Iganmentioning

confidence: 99%

Thrombotic microangiopathy in IgA nephropathy: pathophysiology, histopathology, and treatment perspectives

Rastegar-Kashkouli,

Jafari,

Shahrokh

et al. 2024

J Nephropathol

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“…The clinical presentation of IgAN can vary greatly, encompassing a wide spectrum of manifestations. These can range from no apparent symptoms, such as the presence of asymptomatic hematuria and proteinuria, to gross hematuria accompanied by a rapid decline in kidney function [3]. Renal biopsy is considered the gold standard for diagnosis of IgAN.…”

Section: Introductionmentioning

confidence: 99%

Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis

Chronopoulou,

Tziastoudi,

Pissas

et al. 2023

IJMS

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The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (>2 g/24 h) and/or impaired kidney function (serum creatinine > 1.5 mg/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09–4.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545–11.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.

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The current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review

Davies,

Chetwynd,

McDowell

et al. 2024

J Nephrol

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Background Glomerulonephritis inherently leads to the development of chronic kidney disease. It is the second most common diagnosis in patients requiring renal replacement therapy in the United Kingdom. Metabolomics and proteomics can characterise, identify and quantify an individual’s protein and metabolite make-up. These techniques have been optimised and can be performed on samples including kidney tissue, blood and urine. Utilising omic techniques in nephrology can uncover disease pathophysiology and transform the diagnostics and treatment options for glomerulonephritis. Objectives To evaluate the utility of metabolomics and proteomics using mass spectrometry and nuclear magnetic resonance in glomerulonephritis. Methods The systematic review was registered on PROSPERO (CRD42023442092). Standard and extensive Cochrane search methods were used. The latest search date was March 2023. Participants were of any age with a histological diagnosis of glomerulonephritis. Descriptive analysis was performed, and data presented in tabular form. An area under the curve or p-value was presented for potential biomarkers discovered. Results Twenty-seven studies were included (metabolomics (n = 9)), and (proteomics (n = 18)) with 1818 participants. The samples analysed were urine (n = 19) blood (n = 4) and biopsy (n = 6). The typical outcome themes were potential biomarkers, disease phenotype, risk of progression and treatment response. Conclusion This review shows the potential of metabolomic and proteomic analysis to discover new disease biomarkers that may influence diagnostics and disease management. Further larger-scale research is required to establish the validity of the study outcomes, including the several proposed biomarkers. Graphical abstract

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Omics are Getting Us Closer to Understanding IgA Nephropathy

Cited by 5 publications

References 114 publications

Thrombotic microangiopathy in IgA nephropathy: pathophysiology, histopathology, and treatment perspectives

Thrombotic microangiopathy in IgA nephropathy: pathophysiology, histopathology, and treatment perspectives

Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis

The current use of proteomics and metabolomics in glomerulonephritis: a systematic literature review

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