Is there a role for immunosuppression in immunoglobulin A nephropathy?

Al-Lawati, Ali I.; Reich, Heather N.

doi:10.1093/ndt/gfw342

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…Considering a number of adverse effects, immunosuppression should be prescribed only for patients at the highest risk of developing ESRD [85]. Al-Lawati et al suggested that immunosuppressive drugs in IgAN ought to modulate immune responses, including Gd-IgA1 production, glomerular and tubulointerstitial inflammation, and mesangial and endothelial cell proliferation [85].…”

Section: T Cells As a Therapeutic Target Of Traditional And Biologicamentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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Background Immunoglobulin A nephropathy (IgAN), the most frequent cause of primary glomerulonephritis worldwide, is an autoimmune disease with complex pathogenesis. In this review, we focus on T cells and summarize knowledge about their involvement in pathophysiology and treatment of IgAN Methods We reviewed the literature for (1) alterations of T cell subpopulations in IgAN, (2) experimental and clinical proofs for T cells’ participation in IgAN pathogenesis, (3) clinical correlations with T cell-associated alterations, and (4) influence of drugs used in IgAN therapy on T cell subpopulations. Results We found that IgAN is characterized by higher proportions of circulatory Th2, Tfh, Th17, Th22 and γδ T cells, but lower Th1 and Treg cells. We discuss genetic and epigenetic makeup that may contribute to this immunological phenotype. We found that Th2, Th17 and Tfh-type interleukins contribute to elevated synthesis of galactose-deficient IgA1 (Gd-IgA1) and that the production of anti-Gd-IgA1 autoantibodies may be stimulated by Tfh cells. We described the roles of Th2, Th17, Th22 and Treg cells in the renal injury and summarized correlations between T cell-associated alterations and clinical features of IgAN (proteinuria, reduced GFR, hematuria). We detailed the impact of immunosuppressive drugs on T cell subpopulations and found that the majority of drugs have nonoptimal influence on T cells in IgAN patients. Conclusions T cells play an important role in IgAN pathogenesis and are correlated with its clinical severity. Clinical trials with the drugs targeting the reported alterations of the T-cell compartment are highly desirable.

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Section: T Cells As a Therapeutic Target Of Traditional And Biologicamentioning

confidence: 99%

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

et al. 2018

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“…However, no recommendation was made for patients with eGFR < 45 ml/min/1.73m 2 . Given that some studies supported the use of steroids or immunosuppressants [7][8][9] for these patients, which is also widely applied clinically, thus we conducted this study to explore whether corticosteroids or immunosuppressant therapies could improve the renal outcome of patients with advanced IgAN (eGFR < 45 mL/min/1.73 m 2 and mean proteinuria > 1 g/24h).…”

Section: Introductionmentioning

confidence: 99%

Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in Chinese Patients with Advanced IgA Nephropathy

Tang

Peng

et al. 2018

Kidney Blood Press Res

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Background/Aims: Treatment of advanced Immunoglobulin A nephropathy (IgAN) patients with estimated glomerular filtration rate (eGFR) below 45 mL/min per 1.73 m² remains inconsistent. The aim of this study is to compare the effects of corticosteroid and immunosuppressant therapies among these patients. Methods: A total of 201 adult patients with advanced IgAN (eGFR < 45 mL/min/1.73 m² and proteinuria > 1 g/24h at biopsy) grouped into supportive care (SC), steroids alone (CS), and steroids plus immunosuppressant (IT) groups, were investigated between 30^th December 2002 and 30^th June 2016. The primary endpoint was the combined endpoint of a 50% decline in eGFR and/or end stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m² or maintenance renal replacement treatment). Responses to therapy included complete remission (CR: urinary protein excretion < 0.5 g/24h, with eGFR decrease less than 10% baseline), partial remission (PR: proteinuria decrease by > 50% baseline, with eGFR decrease less than 10% baseline), no response (NR: proteinuria decrease < 50% baseline, or eGFR decrease > 10% baseline) and ESRD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: During the follow-up period (37.2 ± 22.7 months), 6.8% patients in SC group, 25.0% in CS group, and 38.0% in IT group achieved CR or PR, while 78.4%, 62.5% and 49.3% patients in these 3 groups reached primary endpoint respectively (p < 0.001). Three-year renal survival rates in SC and combined immunosuppressive treatment groups (CS and IT groups) were 33.8% vs 51.2% (p = 0.02), and 5-year renal survival rates were 12.2% vs 21.3% (p = 0.1) respectively. Multivariate Cox regression analysis showed that hypertension (HR = 2.44, 95% CI 1.51–3.95; p < 0.001), Scr (HR = 1.01, 95% CI 1.00-1.01; p < 0.001), T1-T2 lesion (HR = 1.99, 95% CI 1.35–2.93; p = 0.001) were independent indicators of poor renal outcome. Conclusion: Immunosuppressive treatment (CS and IT therapy) may improve short-term renal outcome compared with supportive treatment in advanced IgAN patients.

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“…Specifically, it was found, that during the first six post-transplant months, the area under the receiver operating characteristic curve of prednisone was significantly associated with the decrease of Gd-IgA1 and IgA1, whereas area under the receiver operating characteristic curve of tacrolimus was associated with the decrease of IgA1 in the same period. A meta-analysis revealed that tacrolimus combined with low-dose glucocorticoids is an effective and safe therapeutic option for the treatment of IgAN in native kidneys as well [ 36 ]. Exploitation of tacrolimus in patients with refractory IgAN has also been tried with promising results [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression

et al. 2021

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Objectives Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. Methods Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN). Results At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others. Conclusion Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

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Is there a role for immunosuppression in immunoglobulin A nephropathy?

Cited by 10 publications

References 36 publications

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

T cells in IgA nephropathy: role in pathogenesis, clinical significance and potential therapeutic target

Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in Chinese Patients with Advanced IgA Nephropathy

Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression

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