Treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy

Kawasaki, Yukihiko

doi:10.1007/s10157-022-02187-z

Cited by 3 publications

(3 citation statements)

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“…Macrophages are known as heterogeneous populations, which are subdivided into different groups based on their surface molecules and functions ( 16 ). In IgAN, these groups of macrophages might exist differently and have diverse effects on the renal injury of IgAN ( 17 ). M1 macrophages are correlated to proinflammatory reactions in the acute phase, during the first 48 h after an acute kidney injury (AKI), while M2 macrophages, which are relevant to chronic inflammation, take part in tissue repair and remodeling and dominate at later time points ( 18 , 19 ).…”

Section: The Macrophage Subpopulations and Their Functions In Iganmentioning

confidence: 99%

“…Macrophages also can participate in the immune response by activating the T cell as an antigen-presenting cell, leading to cell necrosis, mesangial cell proliferation, extracellular matrix dilatation, and crescent formation. Macrophages that infiltrate the glomeruli can be involved in the progress of par mesangial destructive injury or decline of glomerular basement membrane (GBM) ( 17 ) and the destruction of the completeness of podocyte. The podocyte is damaged by various inflammatory cascades, immune responses, and oxidative stress.…”

Section: The Role Of Mononuclear Phagocyte System In Glomerulimentioning

confidence: 99%

“…There were 12 articles on IgAN concerning the infiltration of macrophages in the glomeruli, and 87.5% of the patients belonged to the M1 according to the Oxford MEST-C. Hematuria and proteinuria are usual symptoms in IgAN patients. Kawasaki et al showed the connection between the clinical manifestations of 41 patients with the infiltration of macrophages by renal biopsy (17). The average number of glomerular macrophages per patient (ANM/P) is linked with the severity of hematuria and leukocyturia positively (p < 0.01) (29), and the macrophage subtypes were associated with pathological subclasses according to MEST-C. CD68 + macrophage counts per glomerulus were related with C (r = 0.346), M (r = 0.325), and final MEST-C sum scores (r = 0.337) (12).…”

Section: The Relationship Between Different Subtypes Of Macrophages A...mentioning

confidence: 99%

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The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis

Liu

Gong

2023

Front. Immunol.

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Although the “multiple hits” theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-β (TGF-β), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule.

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Section: The Macrophage Subpopulations and Their Functions In Iganmentioning

confidence: 99%

Section: The Role Of Mononuclear Phagocyte System In Glomerulimentioning

confidence: 99%

Section: The Relationship Between Different Subtypes Of Macrophages A...mentioning

confidence: 99%

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The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis

Liu

Gong

2023

Front. Immunol.

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Current treatment status of IgA nephropathy in Japan: a questionnaire survey

Matsuzaki,

Suzuki,

Kikuchi

et al. 2023

Clin Exp Nephrol

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Background In 2020, the Committee of Clinical Practical Guideline for IgA Nephropathy (IgAN) revised the clinical practice guidelines. Herein, we conducted a questionnaire survey to assess the potential discrepancies between clinical practice guidelines and real-world practice in Japan. Methods A web-based survey of members of the Japanese Society of Nephrology was conducted between November 15 and December 28, 2021. Results A total of 217 members (internal physicians: 203, pediatricians: 14) responded to the questionnaire. Of these respondents, 94.0% answered that the clinical practice guidelines were referred to “always” or “often.” Approximately 66.4% respondents answered that histological grade (H-Grade) derived from the “Clinical Guidelines for IgA nephropathy in Japan, 3rd version” and the “Oxford classification” were used for pathological classification. Moreover, 73.7% respondents answered that the risk grade (R-grade) derived from the “Clinical Guidelines for IgA nephropathy in Japan, 3rd version” was referred to for risk stratification. The prescription rate of renin–angiotensin system blockers increased based on urinary protein levels (> 1.0 g/day: 88.6%, 0.5–1.0 g/day: 71.0%, < 0.5 g/day: 25.0%). Similarly, the prescription rate of corticosteroids increased according to proteinuria levels (> 1.0 g/day: 77.8%, 0.5–1.0 g/day: 52.8%, < 0.5 g/day: 11.9%). The respondents emphasized on hematuria when using corticosteroids. In cases of hematuria, the indication rate for corticosteroids was higher than in those without hematuria, even if the urinary protein level was 1 g/gCr or less. Few severe infectious diseases or serious deterioration in glycemic control were reported during corticosteroid use. Conclusion Our questionnaire survey revealed real-world aspects of IgAN treatment in Japan.

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Causal relationship between gut microbiota, circulating inflammatory proteins and IgA nephropathy: two-sample and mediated Mendelian randomisation analysis

Dong,

Li,

Feng

et al. 2024

Preprint

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Background：IgA nephropathy (IgAN) is an immune-inflammatory glomerulonephritis mediated by both genetic and environmental factors. Recent research indicates a close association between gut microbiota dysbiosis and IgAN development. Additionally, circulating inflammatory proteins also play a significant role in the progression of IgAN.However, the causal relationship among gut microbiota, circulating inflammatory proteins, and IgAN remains unclear. Methods：This study utilized publicly available genome-wide association study (GWAS) data for Mendelian randomization (MR) analysis to investigate the causal relationship among gut microbiota circulating inflammatory proteins and IgAN, as well as to examine the mediating role of circulating inflammatory proteins in the association between gut microbiota and IgAN. The primary analytical method employed in this study was inverse variance-weighted (IVW) analysis with specific attention given to Bayesian-weighted MR results and supported by MR-Egger regression, weighted median, median model and simple model approaches. Several sensitivity analyses were performed to evaluate the robustness of MR analysis findings. Results：(1)MR analysis of gut microbiota and IgAN indicates negative associations between g_Roseburia, g_Faecalibacterium, s_Odoribacter_splanchnicus, and s_Roseburia_unclassified with IgAN risk, while positive associations exist between s_Paraprevotella_unclassified and s_Lachnospiraceae_bacterium_7_1_58FAA with IgAN risk.(2) Circulating inflammatory proteins to IgAN in MR analysis showed that IL-10RA was negatively correlated with the risk of IgAN, while TSGP-CD5, FGF23, LIF, and TGF-α levels were positively correlated with the risk of IgAN.(3)Mediation analysis suggests that TGF-αserves as a mediator between s_Odoribacter_splanchnicus and the causality of IgAN. (4) The results of the reverse MR analysis suggest no significant causal effect of IgAN on gut flora and circulating inflammatory proteins.Sensitivity analyses consistently support the reliability of the study results. Conclusion：Our research findings, obtained through genetic methods, substantiate the causal link between gut microbiota, circulating inflammatory proteins, and IgAN. The identification of biomarkers offers novel insights into the potential mechanisms underlying IgAN, which can be advantageous for early diagnosis and the development of more effective treatment strategies.

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Treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy

Cited by 3 publications

References 70 publications

The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis

The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis

Current treatment status of IgA nephropathy in Japan: a questionnaire survey

Causal relationship between gut microbiota, circulating inflammatory proteins and IgA nephropathy: two-sample and mediated Mendelian randomisation analysis

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