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Current treatment of IgA nephropathy.

ABSTRACT: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia and the Western world. In most patients, it follows an asymptomatic to oligosymptomatic course and GFR loss, if any, is slow. The mainstay of therapy therefore is optimized supportive care, i.e., measures that lower blood pressure, reduce proteinuria, minimize lifestyle risk factors, and otherwise help to reduce non-specific insults to the kidneys. The value of immunosuppression has become controversial and if at all, systemic high-dose corticosteroid therapy should be considered for a few months taking into account patient characteristics that would caution against or preclude such therapy. In addition, adverse events related to corticosteroid therapy markedly increase as GFR declines. Beyond corticosteroids, there is little evidence that any additional immunosuppression is helpful, with the exception of mycophenolate mofetil in patients of Asian descent. A considerable number of clinical trials ranging from enteric coated budesonide to blockade of B-cell function to complement inhibitors are currently ongoing and will hopefully allow a more targeted therapy of high-risk patients with progressive IgAN in the future.

SUBMITTER: Floege J

PROVIDER: S-EPMC8551131 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Current treatment of IgA nephropathy.

Floege Jürgen J Rauen Thomas T Tang Sydney C W SCW

Seminars in immunopathology 20210908 5

IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia and the Western world. In most patients, it follows an asymptomatic to oligosymptomatic course and GFR loss, if any, is slow. The mainstay of therapy therefore is optimized supportive care, i.e., measures that lower blood pressure, reduce proteinuria, minimize lifestyle risk factors, and otherwise help to reduce non-specific insults to the kidneys. The value of immunosuppression has become controversial and if at all, s ...[more]

PMID: 34495361

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Project description: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 and end-stage renal disease. Current standards of care focus on optimization of antihypertensive and antiproteinuric 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 the 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 signaling pathways of nephritogenic polymeric IgA1 complexes (e.g., signaling of immune receptors via spleen tyrosine kinase) has 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.

Dataset Information

Current treatment of IgA nephropathy.

Publications

Current treatment of IgA nephropathy.

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