Abstract
IgA nephropathy remains the most common primary glomerular disease worldwide. It affects children and adults of all ages, and is a leading cause of end-stage kidney disease, making it a considerable public health issue in many countries. Despite being initially described over 50 years ago, there are still no disease specific treatments, with current management for most patients being focused on lifestyle measures and renin-angiotensin-aldosterone system blockade. However, significant advances in the understanding of its pathogenesis have been made particularly over the past decade, leading to great interest in developing new therapeutic strategies, and a significant rise in the number of interventional clinical trials being performed. In this review, we will summarise the current state of management of IgAN, and then describe major areas of interest where new therapies are at their most advanced stages of development, that include the gut mucosal immune system, B cell signalling, the complement system and non-immune modulators. Finally, we describe clinical trials that are taking place in each area and explore future directions for translational research.
Highlights
IgA nephropathy (IgAN) remains the most common primary glomerular disease in the world
Long-term registry data have shown that patients with IgAN who have preserved kidney function, non-visible haematuria and minimal proteinuria
Forthcoming Kidney Disease: Improving Global Outcomes (KDIGO) guidelines emphasize that patients with IgAN who have proteinuria >1 g/day despite 90 days of optimized supportive care can be considered for corticosteroid therapy, their clinical benefit is not established, and that it is much preferred that such patients be offered an opportunity to take part in a therapeutic clinical trial
Summary
IgA nephropathy (IgAN) remains the most common primary glomerular disease in the world. It often affects younger adults, and in approximately 30% of patients it progresses to end-stage kidney disease (ESKD) within 20 years of diagnosis, placing a considerable burden on individuals, carers and healthcare systems globally. Over the past few decades, significant advances have been made in understanding the complex pathogenesis that underlies IgAN. This has driven an explosion of interest in developing new therapeutic strategies for this condition, and several global phase II and phase III clinical trials are currently underway. We will focus on current treatment guidelines and new therapies for IgAN that range from being in the initial stages of development to the late phases of clinical trials
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