IgA Nephropathy

Rodrigues, Jennifer C.; Haas, Mark; Reich, Heather N.

doi:10.2215/cjn.07420716

Cited by 453 publications

(364 citation statements)

References 72 publications

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“…Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis throughout the world [1]. The disease is characterized by the deposition predominantly of IgA in the mesangium, whereas histological changes of IgAN on light microscopy may vary greatly among patients.…”

Section: Introductionmentioning

confidence: 99%

Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

Zhang

Sun

Zhou

et al. 2018

Kidney Blood Press Res

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Background/Aims: Arterial fibrotic intimal thickening and arteriolar hyaline are considered common pathological features in immunoglobulin A nephropathy (IgAN), whereas little is known about the acute pathological manifestations of endothelial cell injury. The aim of this study was to investigate characteristics of intrarenal arterial lesions and to estimate their prognostic values in patients with IgAN. The primary renal endpoint was a 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). Methods: Various renal arterial lesions (arterial fibrotic intimal thickening, arteriolar hyaline, arteriolar endotheliocyte swelling, arteriolar inflammatory cell infiltration, and arteriolar thrombosis) in 1683 patients with IgAN were reviewed and reclassified using a semi-quantitative scoring system. Their correlations with clinical features, pathological characteristics, and renal outcomes were evaluated. Results: The prevalence of intrarenal arterial lesions was up to 72.2% in IgAN patients. There were 978 patients (58.1%) with arterial fibrotic intimal thickening, 350 patients (20.8%) with arteriolar hyaline, 432 patients (25.7%) with arteriolar endotheliocyte swelling, 356 patients (21.2%) with arteriolar inflammatory cell infiltration and 43 patients (2.6%) with arteriolar thrombosis. Arterial fibrotic intimal thickening and arteriolar hyaline were strongly associated with higher mean arterial pressure (MAP) and reduced eGFR (P < 0.001) but were not related to proteinuria at the time of renal biopsy. In contrast, arteriolar endotheliocyte swelling and arteriolar thrombosis were correlated with heavier proteinuria as well as higher MAP and reduced eGFR. During follow-up, patients with vascular lesions received more renin-angiotensin system (RAS) blockade and less glucocorticoid and showed poorer renal outcomes. Univariate Cox model showed that the presence of renal vascular lesions [hazard ratio (HR) = 25.01, 95% confidence interval (CI): 6.19 to 101.03, P < 0.001] was a risk factor for renal outcomes. However, in multivariable Cox analysis, which included clinical factors and the Oxford-MEST-C, vascular lesions were not significantly associated with an increased risk of renal failure. Remarkably, the impact of vascular lesions on the survival from ESRD or 50% reduction in renal function was eliminated by the use of RAS blockade after adjustment for eGFR, proteinuria, and MAP. Conclusion: Our study demonstrates the high prevalence of vascular lesions, including the chronic and acute arterial pathological changes, in patients with IgAN. The presence of vascular lesions is associated with higher MAP, reduced eGFR and poorer renal outcomes, which could be influenced by the RAS blockade treatment.

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Section: Introductionmentioning

confidence: 99%

Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

Zhang

Sun

Zhou

et al. 2018

Kidney Blood Press Res

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“…IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease [1, 2]. The immunopathogenesis of IgAN involves an aberrant O-galactosylation of IgA1 molecules, production of O-glycan-specific autoantibodies and formation of nephritogenic immune complexes that deposit in the glomerular mesangium and evoke glomerular injury [3].…”

Section: Introductionmentioning

confidence: 99%

CTLA-4 Polymorphisms in Patients with IgA Nephropathy Correlate with Proteinuria

Jacob

Ohl

Goodarzi

et al. 2018

Kidney Blood Press Res

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Background/Aims: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and still constitutes one of the most important causes of end-stage renal disease. Abnormal T cell responses may play a role in IgAN pathogenesis. Co-stimulatory molecules such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are important for naive T cells to initiate and terminate immune responses. Single nucleotide polymorphisms (SNPs) in the CTLA4 gene locus are associated with several autoimmune diseases. Methods: We aimed to investigate the occurrence of the SNPs -318C/T, +49A/G and CT60 G/A within the CTLA4 locus in healthy blood donors (n=455) and IgAN patients (n=252) recruited from the recently published STOP-IgAN trial. The presence of these SNPs was then associated with baseline proteinuria in IgAN patients. Results: We observed a significantly increased frequency of the CTLA4 -318C/T genotype in IgAN patients as compared to controls (CC vs. CT+TT: OR 1.65, 95%-CI 1.03-2.65, p=0.035). No significant associations, neither with the +49A/G nor for the CT60 G/A SNP, were detected. However, when we stratified for proteinuria at time of inclusion into the STOP-IgAN trial (<1 g/day vs. >1 g/day), we observed significant differences in the frequencies of the CT60 G/A genotype, i.e. a significantly increased risk for higher proteinuria in patients carrying the G allele (OR 2.81, 95%-CI 1.03-7.64, p=0.042). Conclusion: The CTLA4 -318/C/T SNP was associated with an increased risk to develop IgAN, while the CT60 G/A genotype significantly associated with the risk for higher proteinuria suggesting a possible role for CTLA-4 in IgAN.

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“…IgA nephropathy is a glomerular disease that is common worldwide (1). It is characterized by mesangial expansion, high serum IgA levels, and IgA deposition in the glomerulus; however, its pathogenic and progressive factors have not been fully elucidated (2, 3). Although the progression of IgA nephropathy is not rapid, the renal functions of subjects with IgA nephropathy decline progressively, and ∼40% of patients reportedly progress to renal failure in 20 yr (4).…”

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confidence: 99%

Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice

et al. 2019

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Because the association between sphingosine 1‐phosphate (S1P)/apolipoprotein M (ApoM) and chronic kidney diseases has not been established, we investigated the involvement of S1P/ApoM in the phenotypes of IgA nephropathy in hyper‐IgA (HIGA) mice. The overexpression of ApoM in adenoviral gene transfer ameliorated the phenotypes of IgA nephropathy in HIGA mice, whereas the knockdown of ApoM with siRNA caused deterioration. When ApoM‐overexpressing HIGA mice were treated with VPC23019, an antagonist against S1P receptor 1 (S1P1) and 3 (S1P3), we observed that the protective effects of ApoM were reversed, whereas JTE013, an antagonist against S1P2, did not inhibit the effects. We also found that S1P bound to albumin accelerated the proliferation of MES13 cells and the fibrotic changes of HK2 cells, which were inhibited by JTE013, whereas S1P bound to ApoM suppressed these changes, which were inhibited by VPC23019. These results suggest that S1P bound to ApoM possesses properties protective against the phenotypes of IgA nephropathy through S1P1 and S1P3, whereas S1P bound to albumin exerts deteriorating effects through S1P2. ApoM may be useful as a therapeutic target to treat or retard the progression of IgA nephropathy.—Kurano, M., Tsuneyama, K., Morimoto, Y., Nishikawa, M., Yatomi, Y. Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice. FASEB J. 33, 5181–5195 (2019). http://www.fasebj.org

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IgA Nephropathy

Cited by 453 publications

References 72 publications

Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

CTLA-4 Polymorphisms in Patients with IgA Nephropathy Correlate with Proteinuria

Apolipoprotein M suppresses the phenotypes of IgA nephropathy in hyper‐IgA mice

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