Primary IgA nephropathy: current challenges and future prospects
File(s)
Author(s)
Tam, FWK
Penfold, Rose S
Prendecki, Maria
McAdoo, Stephen
Type
Journal Article
Abstract
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, exhibiting a variable clinical and pathological course and significantly contributing to the global burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Current standards of care focus on optimization of anti-hypertensive and anti-proteinuric therapies (typically renin-angiotensin system blockade) to reduce disease progression. Much recent attention has focused on whether additional immunosuppression confers better outcomes than supportive management alone and indeed several trials have demonstrated renoprotective effects following use of oral corticosteroids. However, results have been inconsistent and perceived benefits must be balanced against risks and adverse effects associated with generalized immunosuppression, as highlighted by the high-profile STOP-IgAN and TESTING clinical trials. Recent translational research in vitro and animal models of IgAN have generated greater insight into potential therapeutic targets for this complex autoimmune disease. Deeper understanding of the roles of the mucosal immune barrier, complement activation and deposition, T-cell dependent and independent mechanisms of B cell activation, and of the deposition and downstream inflammatory signalling pathways of nephritogenic polymeric IgA1 complexes (eg. signaling of immune receptors via Syk) have formed the rationale for the development of novel agents and clinical trials of more targeted therapies. However, translating findings into clinical practice is challenging, with many immunopathological features of IgAN specific to humans.
Recent comprehensive reviews outline current understanding of mechanisms of IgAN as well as ongoing and future clinical trials; it is not our aim to replicate this here. Instead, we take a mechanistic approach to current treatment strategies, outlining advantages and limitations of each before exploring ongoing research with potential translation into future targeted therapies for this complex disease.
Recent comprehensive reviews outline current understanding of mechanisms of IgAN as well as ongoing and future clinical trials; it is not our aim to replicate this here. Instead, we take a mechanistic approach to current treatment strategies, outlining advantages and limitations of each before exploring ongoing research with potential translation into future targeted therapies for this complex disease.
Date Issued
2018-04-12
Date Acceptance
2018-01-12
Citation
International Journal of Nephrology and Renovascular Disease
ISSN
1178-7058
Publisher
Dove Medical Press
Start Page
137
End Page
148
Journal / Book Title
International Journal of Nephrology and Renovascular Disease
Volume
11
Copyright Statement
© 2018 Penfold et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.
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you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work
you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For
permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Sponsor
Kidney Research UK
Medical Research Council (MRC)
Grant Number
SP/MEKC/5/2014
MR/M018733/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
IgA nephropathy
glomerulonephritis
immunosuppression
chronic kidney disease
Syk
complement
RANDOMIZED CONTROLLED-TRIAL
RENIN-ANGIOTENSIN SYSTEM
GALACTOSE-DEFICIENT IGA1
SPLEEN TYROSINE KINASE
STAGE RENAL-DISEASE
COMPLEMENT FACTOR-H
MYCOPHENOLATE-MOFETIL
KIDNEY-TRANSPLANTATION
COMBINATION THERAPY
CYCLOPHOSPHAMIDE THERAPY
1103 Clinical Sciences
1102 Cardiovascular Medicine And Haematology
Publication Status
Published
Date Publish Online
2018-04-12