An Update on Targeted Treatment of IgA Nephropathy: An Autoimmune Perspective

Huang, Xin; Xu, Gaosi

doi:10.3389/fphar.2021.715253

Cited by 30 publications

(21 citation statements)

References 125 publications

(135 reference statements)

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“…Encouragingly, targeted-release budesonide as a novel form of steroid therapy has been a research focus. Nefecon is an oral targeted release steroid, which mainly acts on the terminal ileum to exert immunosuppressive effects, and thereby the AEs of systemic steroid therapy are alleviated to some extent [ 2 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

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The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov

Cui

Zhai

et al. 2022

Renal Failure

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Objectives IgA Nephropathy (IgAN) is common chronic kidney disease with a high incidence. This study aims to analyze comprehensively therapeutic clinical trials for IgAN registered on ClinicalTrials.gov. Methods Therapeutic trials for IgAN registered on ClinicalTrials.gov. up to 15 August 2021 were obtained. The general characteristics, features of experimental design, treatment strategies, and some main inclusion criteria and outcome measures were accessed. Results A total of 104 therapeutic clinical trials for IgAN were extracted on ClinicalTrials.gov up to 15 August 2021. Most of these trials explored the treatment for primary IgAN confirmed by renal biopsy in adults. Only 9% of all selected trials had results. Forty-five percent of trials recruited 50 or fewer participants, and 73% were adults or older adults. 99% of trials were interventional studies, and of all the interventional trials, 70% of trials were randomized, and 68% exercised a parallel assignment of intervention model. Immunosuppression was the most studied for the treatment of IgAN. Moreover, many novel agents had been increasingly studied in recent years. Furthermore, the inclusion criteria and primary outcome measures in these trials were diverse, and the level of proteinuria and change of proteinuria levels were the most used as inclusion criteria and primary outcome, respectively. Conclusions The majority of therapeutic trials for IgAN were randomized, none masking and parallel-assignment interventional studies, primarily recruiting adult patients as research subjects. These trials had relatively small sample sizes and short observation. Thus, more large-scale, multicenter, and randomized controlled trials are still needed to improve the management for IgAN.

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Section: Discussionmentioning

confidence: 99%

“…Factor B (FB) is an essential component of complement activation by AP. LNP023 is an agent that can selectively block FB, thus preventing the complement activation by AP, which may contribute to alleviating disease progression [ 25 , 27 ]. OMS721 is an antibody targeting MASP-2, a protease involved in the complement activation by LP.…”

Section: Discussionmentioning

confidence: 99%

The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov

Cui

Zhai

et al. 2022

Renal Failure

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“…IgAN is an important cause of end-stage renal disease in young people. However, the disease cannot be treated effectively and selectively, and most treatment strategies are based on controlling blood pressure and relieving proteinuria to slow disease progression ( Leung et al, 2018 ; Huang and Xu 2021 ). Albuminuria is considered as the most widely and well-studied risk factor for IgAN progression to end-stage kidney disease ( Thompson et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

et al. 2022

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Background: Immunoglobulin A nephropathy (IgAN) is the most common glomerular disease worldwide. Its pathological features include IgA immune complex deposition, accompanied by mesangial cell proliferation and mesangial matrix expansion. This study was conducted to investigate the effects of Liuwei Dihuang pills (LWDHW) on IgAN in mice and human podocytes, as well as to determine their underlying mechanisms of action.Methods: For in vitro experiments, podocytes were exposed to the human mesangial cell culture medium supernatant of glomerular cells treated with aggregated IgA1 (aIgA1) and LWDHW-containing serum. Cell viability and the proportion of positive cells were evaluated using CCK-8 and flow apoptosis kits, respectively. The cells were collected for western blot analysis. Twenty-four mice with IgAN induced by oral bovine serum albumin administration combined with tail vein injection of staphylococcal enterotoxin B were randomly divided into four groups of six mice each: untreated model group, model + LWDHW group, model + rapamycin group, and model + LWDHW + rapamycin group. The normal control group contained six mice. The red blood cell count in the urine, urine protein, blood urea nitrogen, serum creatinine, and IgA deposition were determined, and TUNEL and western blotting were performed in the mouse kidney tissues.Results:In vitro experiments showed that LWDHW promoted autophagy by regulating the PI3K/Akt/mTOR signalling pathway and improved the damage to podocytes caused by the aIgA1-treated mesangial cell supernatant. This study demonstrates the effectiveness of LWDHW for treating IgAN. In the animal experiments, LWDHW significantly reduced the urine red blood cell count, serum creatinine and urea nitrogen contents, and 24 h urinary protein function and improved IgA deposition in the kidney tissues, glomerular volume, glomerular cell proliferation and polysaccharide deposition, and glomerular cell apoptosis. The pills also reversed the changes in the LC3II/I ratio and p62 content in the kidney tissues. The combination of LWDHW and rapamycin showed stronger inhibitory effects compared to those of LWDHW or rapamycin alone.Conclusion: LWDHW may improve regulation of the PI3K-Akt-mTOR pathway and inhibit autophagy in podocytes, as well as alleviate IgA nephropathy by directly altering mesangial cell exosomes.

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“…IgA nephropathy is usually considered to be an immune complex-induced or polymerized IgA1-induced glomerulonephritis [57][58][59][60]. Zhong et al [61] reported that although α-diversity exhibited no significant differences in taxon richness and evenness, there was a clear separation in the composition of gut microbiota between patients with IgA nephropathy and healthy controls, indicating that the diversity of gut microbiota was altered in patients with IgA nephropathy.…”

Section: Iga Nephropathymentioning

confidence: 99%

Recent advances of gut microbiota in chronic kidney disease patients

Zhao

2022

Exploration of Medicine

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Chronic kidney disease (CKD) is a worldwide public health issue and has ultimately progressed to an end-stage renal disease that requires life-long dialysis or renal transplantation. However, the underlying molecular mechanism of these pathological development and progression remains to be fully understood. The human gut microbiota is made up of approximately 100 trillion microbial cells including anaerobic and aerobic species. In recent years, more and more evidence has indicated a clear association between dysbiosis of gut microbiota and CKD including immunoglobulin A (IgA) nephropathy, diabetic kidney disease, membranous nephropathy, chronic renal failure and end-stage renal disease. The current review describes gut microbial dysbiosis and metabolites in patients with CKD thus helping to understand human disease. Treatment with prebiotics, probiotics and natural products can attenuate CKD through improving dysbiosis of gut microbiota, indicating a novel intervention strategy in patients with CKD. This review also discusses therapeutic options, such as prebiotics, probiotics and natural products, for targeting dysbiosis of gut microbiota in patients to provide more specific concept-driven therapy strategy for CKD treatment.

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An Update on Targeted Treatment of IgA Nephropathy: An Autoimmune Perspective

Cited by 30 publications

References 125 publications

The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov

The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov

Liuwei Dihuang Pills Inhibit Podocyte Injury and Alleviate IgA Nephropathy by Directly Altering Mesangial Cell-Derived Exosome Function and Secretion

Recent advances of gut microbiota in chronic kidney disease patients

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