Novel agents for treating IgA nephropathy

Abstract

Purpose of reviewIn the past, the treatment of IgA nephropathy (IgAN), which is the most common glomerulonephritis worldwide, mostly relied on blockade of the renin–angiotensin system as a central component of so-called supportive therapy as well as on high-dose systemic corticosteroid therapy.Recent findingsThe supportive treatment arm has been expanded by the addition of sodium-glucose cotransporter-2 inhibitors, hydroxychloroquine, and, most recently, endothelin A receptor blockers. Treatment with high-dose systemic corticosteroids has become more controversial, with some studies observing no benefit and others documenting the protection of kidney function. However, all recent studies on systemic corticosteroids consistently found significant toxicity. An important novel approach to IgAN, therefore, is therapy with a targeted release formulation of budesonide with preferential release in the distal small intestine, given the mounting evidence for a gut–kidney axis in the pathophysiology of IgAN. In addition, emerging new therapeutic options include a variety of complement inhibitors as well as agents targeting B-cell proliferation and differentiation.SummaryIn recent years, IgAN has become the focus of a considerable number of clinical studies that will significantly advance the development of new therapy strategies.

Clinical Practice Patterns in IgA Nephropathy: A Global Questionnaire-Based Survey

“…To date, 2 new drugs have been recently approved for treating IgAN at high risk of progression (i.e., urine protein-to-creatinine ratio >1.5 mg/g), a targeted release formulation of budesonide, and sparsentan, an endothelin-1 receptor A inhibitor plus angiotensin II receptor antagonist. 25 The extent to which these new therapies will actually change how IgAN is managed will depend largely on their availability and affordability especially in economically disadvantaged populations. Also, any updated guidelines should focus on step-wise inclusion of these drugs only when absolutely required as their long-term use in this smoldering disease may pose a significant financial burden on patients especially in LMICs which do not provide universal health care.…”

Endothelin System in Hypertension and Chronic Kidney Disease

“…For example, considerable preclinical data have shown an important role for ET A R within the glomerulus to induce focal segmental sclerosis in a variety of kidney disease models, including diabetic 31 and sickle cell nephropathy, 32 and also interstitial fibrosis throughout the renal parenchyma even in the absence of hypertension (Figure 4). 33 Ongoing trials using ETRAs include several focusing specifically on IgAN 34 and other CKDs, as described below.…”

Deciphering roles of protein post-translational modifications in IgA nephropathy progression and potential therapy

“…The treatments of IgAN reduce its symptoms, prevent its complications and retard its progression. The therapeutic strategy of IgAN includes immunosuppressive therapy to suppress the immune system and reduce inflammation, supportive care, dietary modification, blood pressure control and prevention of complications [10][11][12][13].…”