An Update on the Current State of Management and Clinical Trials for IgA Nephropathy

Cheung, Chee Kay; Rajasekaran, Arun; Barratt, Jonathan; Rizk, Dana V.

doi:10.3390/jcm10112493

Cited by 42 publications

(45 citation statements)

References 107 publications

(122 reference statements)

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“…e incidence of autoimmune diseases has been increasing in recent years, and with it, the use of glucocorticoids has become more widespread [37]. e abuse of glucocorticoids has been accompanied by adverse effects of hormones such as femoral head necrosis, diabetes mellitus, and severe fatal infections, making the overall cost of the disease higher, and some patients are unable to tolerate them, refusing to take them, and easily giving up treatment and increasing the risk of disease progression.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis

Chen¹,

Zhang²,

Li³

et al. 2022

Emergency Medicine International

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Background. IgA nephropathy (IgAN) is currently the most common primary glomerular disease, accounting for approximately 36.7% to 58.2% of primary glomerular disease in kidney biopsies in China. Definitive diagnosis depends on immunopathological examination of the kidney. The prognosis of this disease was generally considered to be good, but recent studies have found that about half of patients can progress to end-stage renal disease within 30 years of onset. Because the pathogenesis is unknown, there is no specific treatment. Objective. To evaluate the efficacy and safety of glycosides of Tripterygium wilfordii (GTW) in combination with renin-angiotensin system (RAS) inhibitors for the treatment of IgAN. Methods. Search Embase, Pubmed, Cochrane, CNKI, Web of Science, Wanfang, and VIP for all randomized controlled trials (RCTs) on treating IgAN with RASI from the self-built database to December 2021. Relevant data were searched and collected separately by two reviewers. The Cochrane risk of bias model was used for quality assessment, and RevMan 5.3 was used for data analysis. Results. Thirteen Chinese publications with a total of 958 patients were finally included. There was no statistically significant difference in baseline information (including laboratory data and clinical parameters) between the two groups of patients. The urine protein quantification in both groups showed a significant decreasing trend as the treatment duration increased. At 3, 6, 9, and 12 months after treatment, urine protein was significantly lower than the baseline value in both the observation and control groups (P < 0.05). During the follow-up period, there was no statistical difference in blood creatinine (Scr) and eGFR values between the two groups compared with the baseline values (P > 0.05). Patients with CKD stage 2 achieved a higher remission rate compared with patients with CKD stage 3, with a statistically significant difference (P < 0.05), and the difference between the two groups was not significant for patients in the same stage. There was no statistically significant difference in the total effective rate between the two groups (P > 0.05). During the follow-up period, there was no statistically significant difference in urine protein quantification, Scr, and eGFR between the two groups. In terms of the incidence of adverse reactions, the observation group was less than the control group, and there was a significant difference between the two groups (P < 0.05). Conclusion. GTW combined with RASI is one of the safe and effective treatment modes for IgAN nephropathy. It can not only effectively reduce the excretion of urinary protein in patients and delay the progression of chronic kidney disease but also has less serious side effects and is well tolerated by patients, so it can be a new choice of therapeutic drugs for this group of patients.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis

Chen¹,

Zhang²,

Li³

et al. 2022

Emergency Medicine International

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“…Coincident with this, there is a lack of disease-specific treatment for IgAN and many patients progress to ESKD. Even the new ongoing clinical trials for IgAN target specific areas of the broader disease state [for review, see [183]]. Below, we describe conceptual premises for disease-specific treatment and methods that may allow investigators to get closer to that goal.…”

Section: Iga Nephropathy-disease-specific Treatment Approachesmentioning

confidence: 99%

Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

Knoppová

Reily

King

et al. 2021

JCM

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IgA nephropathy, initially described in 1968 as a kidney disease with glomerular “intercapillary deposits of IgA-IgG”, has no disease-specific treatment and is a common cause of kidney failure. Clinical observations and laboratory analyses suggest that IgA nephropathy is an autoimmune disease wherein the kidneys are damaged as innocent bystanders due to deposition of IgA1-IgG immune complexes from the circulation. A multi-hit hypothesis for the pathogenesis of IgA nephropathy describes four sequential steps in disease development. Specifically, patients with IgA nephropathy have elevated circulating levels of IgA1 with some O-glycans deficient in galactose (galactose-deficient IgA1) and these IgA1 glycoforms are recognized as autoantigens by unique IgG autoantibodies, resulting in formation of circulating immune complexes, some of which deposit in glomeruli and activate mesangial cells to induce kidney injury. This proposed mechanism is supported by observations that (i) glomerular immunodeposits in patients with IgA nephropathy are enriched for galactose-deficient IgA1 glycoforms and the corresponding IgG autoantibodies; (ii) circulatory levels of galactose-deficient IgA1 and IgG autoantibodies predict disease progression; and (iii) pathogenic potential of galactose-deficient IgA1 and IgG autoantibodies was demonstrated in vivo. Thus, a better understanding of the structure–function of these immunoglobulins as autoantibodies and autoantigens will enable development of disease-specific treatments.

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“…Recently, a novel targeted-release form of the corticosteroid budesonide that has been engineered to target the Peyer's patches in the distal ileum, [9][10][11] was approved by the United States Food and Drug Administration (FDA) to become the first disease-specific therapy in IgAN. 12 Herein, we will review the processes that regulate IgA production in the gut mucosa, as well as the evidence that links gut mucosal alterations to IgAN.…”

Section: Introductionmentioning

confidence: 99%

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy

et al. 2022

Self Cite

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Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

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An Update on the Current State of Management and Clinical Trials for IgA Nephropathy

Cited by 42 publications

References 107 publications

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis

Efficacy and Safety of Glycosides of Tripterygium wilfordii Combined with Renin-Angiotensin System in the Treatment of IgA Nephropathy: A Systematic Review and Meta-Analysis

Pathogenesis of IgA Nephropathy: Current Understanding and Implications for Development of Disease-Specific Treatment

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy

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