Corticosteroids for IgA Nephropathy

O’Shaughnessy, Michelle M.; Lafayette, Richard A.

doi:10.1001/jama.2017.9359

Cited by 7 publications

(5 citation statements)

References 16 publications

(25 reference statements)

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“…Recently, there has been a call to tailor treatment with corticosteroids (and other immunomodulatory agents) in IgAN and IgAV to those patients who will receive the most benefit and the least harm. 22 The CureGN cohort will couple the clinical data presented here with detailed histopathology, biomarker, genetic, and longitudinal follow-up data on all its participants. This cohort, therefore, is well positioned to begin to inform these important questions.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Selewski¹,

Ambruzs²,

Appel³

et al. 2018

Kidney International Reports

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IntroductionThe Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.MethodsPatients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.ResultsA total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001).ConclusionThis report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

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Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Selewski¹,

Ambruzs²,

Appel³

et al. 2018

Kidney International Reports

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“…Secondly, anti-IgA1 autoantibodies formed in immunological system. Thirdly, IgA1-containing immune complexes deposited in the glomerular mesangium, which incited nephritogenic inflammatory response ( O’Shaughnessy and Lafayette, 2017 ). The immune deposition leads to mesangial cell proliferate and over-produce components of extracellular matrix, cytokines and chemokines, causing downstream podocyte injury and induce proteinuria ( Lai et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Renin-angiotensin system blockade and immunosuppressive drugs, including corticosteroids have been list in the guideline for the therapy of IgAN (Rasche et al, 2016). Although the use of these drugs was confirmed to reduce the risk of kidney failure and Frontiers in Pharmacology frontiersin.org slow down the progression of renal function in patients with high-risk IgAN, a large proportion of patient was still observed to develop end-stage kidney disease (Lv et al, 2017;O'Shaughnessy and Lafayette, 2017). An "multi-hit" hypothesis of genetic and molecular mechanisms underlying IgAN is undisputed.…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits the proliferation of mesangial cells induced by enzymatically deglycosylated human IgA1 via IgA receptor/MAPK/NF-κB signaling pathway

Song

Chen

et al. 2023

Front. Pharmacol.

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Objective: Despite the use of renin-angiotensin system blockade and immunosuppressive drugs, including corticosteroids, the current treatment regimens for Immunoglobulins A nephropathy (IgAN) are severely limited. The proliferation of mesangial cell and deposition of deglycosylated human IgA1 immune complex are the most common pathologic features of IgAN. We examined the tetrandrine potential of suppressing the proliferation of mesangial cells and explored its underlying mechanisms with a focus on IgA receptor/MAPK/NF-κB signaling pathway.Methods: Standard human IgA (native IgA) were enzymatically desialylated (deS IgA) or further degalactosylated (deS/deGal IgA) using neuraminidase and β-galactosidase. Rat glomerular mesangial cells (HBZY-1) and human renal mesangial cells (HRMC) stimulated by IgA were used to observe the suppressive effect of tetrandrine. The MTT assay was used to detect the cell viability. The protein expression of IgA receptor/MAPK/NF-κB signaling pathway was examined by Western blot. Cell cycle analysis was measured by flow cytometer.Results: Native IgA and deS IgA showed limited stimulation effect on both HBZY-1 cells and HRMCs, whereas deS/deGal IgA significantly stimulated the proliferation of both HBZY-1 cells and HRMCs (p < 0.05). Compared with non-stimulation of deS/deGal IgA, 1–3 μM of tetrandrine had stronger inhibitory effect on the proliferation of HBZY-1 cells and HRMCs with the stimulation of deS/deGal IgA (p < 0.05), suggesting that tetrandrine possibly inhibited the proliferation of mesangial cells induced by deglycosylated human IgA1 specifically. Molecular mechanism study revealed that tetrandrine decreased the expression of IgA1 receptor, CD71 and β4GALT1, and inhibited the activation of MAPK/NF-κB significantly (p < 0.05). Moreover, these inhibitory effect of tetrandrine caused cell cycle arrest and stopped the cell growth in the S phase companied with the upregulating of cyclin A2 and downregulating of cyclin D1.Conclusion: Taken together, tetrandrine inhibited the proliferation of mesangial cells induced by enzymatically deglycosylated human IgA1 via IgA receptor/MAPK/NF-κB signaling pathway. Based on these potential molecular mechanisms, tetrandrine would be an appealing therapeutic option for IgAN.

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“…However, the role of immunosuppression in the management of IgA nephropathy remains highly controversial. The STOP-IgAN and TESTING trials were terminated due to adverse events ( Lv et al, 2017 ; O’Shaughnessy and Lafayette, 2017 ). Therefore, it is of social significance and scientific value to seek new treatment methods.…”

Section: Discussionmentioning

confidence: 99%

Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy

Chang

Yang

et al. 2021

Front. Pharmacol.

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Modified Huangqi Chifeng decoction (MHCD) has been used to reduce proteinuria in immunoglobulin A nephropathy (IgAN) for many years. Previously, we have demonstrated its protective role in glomerular mesangial cells. Podocyte injury, another key factor associated with proteinuria in IgAN, has also attracted increasing attention. However, whether MHCD can reduce proteinuria by protecting podocytes remains unclear. The present study aimed to investigate the protective effects of MHCD against podocyte injury in a rat model of IgAN. To establish the IgAN model, rats were administered bovine serum albumin, carbon tetrachloride, and lipopolysaccharide. MHCD in three doses or telmisartan was administered once daily for 8 weeks (n = 10 rats/group). Rats with IgAN developed proteinuria at week 6, which worsened over time until drug intervention. After drug intervention, MHCD reduced proteinuria and had no effect on liver and kidney function. Furthermore, MHCD alleviated renal pathological lesions, hyperplasia of mesangial cells, mesangial matrix expansion, and podocyte foot process fusion. Western blot analysis revealed that MHCD increased the expression of the podocyte-associated proteins nephrin and podocalyxin. Additionally, we stained podocyte nuclei with an antibody for Wilms’ tumor protein one and found that MHCD increased the podocyte number in rats with IgAN. In conclusion, these results demonstrate that MHCD attenuates proteinuria by reducing podocyte injury.

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Corticosteroids for IgA Nephropathy

Cited by 7 publications

References 16 publications

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Tetrandrine inhibits the proliferation of mesangial cells induced by enzymatically deglycosylated human IgA1 via IgA receptor/MAPK/NF-κB signaling pathway

Modified Huangqi Chifeng Decoction Attenuates Proteinuria by Reducing Podocyte Injury in a Rat Model of Immunoglobulin a Nephropathy

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