All participants in this trial underwent a 6-month run-in period, where an intensive program of supportive care was provided utilizing the measures outlined above. The Supportive versus immunosuppressive Therapy for the treatment of Progressive IgA Nephropathy (STOP-IgAN) trial has provided robust evidence to support this approach. This includes renin-angiotensin-aldosterone system (RAAS) blockade, with either an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), but not both, to the maximum tolerated amount, and addressing overall cardiovascular risk, including strict blood pressure control (to a recommended target of 0.3 g/day and 1 g/day), dietary sodium reduction, smoking cessation if appropriate, weight control, and exercise. The primary focus of management for those who have proteinuria above this threshold should be on optimized goal-directed supportive care. In this review, 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.
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. Over the past few decades, significant advances have been made in understanding the complex pathogenesis that underlies IgAN.
The role of corticosteroids in the management of IgAN is uncertain, and there has been no consistent evidence to support the use of other existing immunosuppressive agents. To date there is no approved disease-specific treatment available. 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. IgA nephropathy (IgAN) remains the most common primary glomerular disease in the world. Finally, we describe clinical trials that are taking place in each area and explore future directions for translational research. 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. 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. 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. 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. IgA nephropathy remains the most common primary glomerular disease worldwide.