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Redefining IgAN Care: Key Updates From the KDIGO 2025 Guideline, With Jonathan Barratt, MD, PhD
Barratt describes the evolving diagnostic and therapeutic landscape of IgAN and breaks down key recommendations from the new KDIGO guidelines.
The field of nephrology has seen several notable advancements in recent years, especially in IgA nephropathy (IgAN). With an improved understanding of the natural history of the disease and the introduction of several new treatment options, identification and management have undergone drastic changes.
Recognizing the changing diagnostic and therapeutic landscape, Kidney Disease: Improving Global Outcomes (KDIGO) released its 2025 Clinical Practice Guideline for the Management of IgAN and immunoglobulin A vasculitis, providing comprehensive, evidence-based recommendations for clinicians managing these kidney diseases and building upon the last update to the IgAN and IgAV management guideline published as part of the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.
For further insight into the significance of these guidelines and their clinical impact, the editorial team of HCPLive Nephrology spoke with guideline author Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in the following Q&A:
HCPLive Nephrology: What recent advances in IgAN necessitated this KDIGO guideline update?
Barratt: I think the data that's been coming out looking at the natural history of IgA nephropathy has really highlighted the poor outcomes for patients living with this disease. A focus of the guideline update has been to promote early diagnosis with early kidney biopsy at low levels of proteinuria, to identify that patients at low level proteinuria are at significant lifetime risk of kidney failure, and that we want nephrologists to think about their treatment and to intervene early.
The goal of treatment has been set to try and return the rate of loss of kidney function back to the healthy population, which is a high bar, but realistically that is the only way we are going to avoid kidney failure in a large number of patients with IgA nephropathy. Of course, the way we assess the loss of kidney function on a clinic by clinic basis is not by the slope of loss of kidney function, because we need longer term data. What we use is proteinuria, and so we have established a much lower proteinuria target this time around, aiming for a proteinuria of < 0.5 grams per day. Ideally, what we want to see is complete remission of proteinuria, so < 0.3 grams.
The overarching theme of this guideline revision is to diagnose early, intervene early, and treat hard with the goal to prevent kidney failure in the lifetime of our patients. We've set up the treatment paradigm to focus on the 2 different aspects of loss of nephrons that we believe are important in IgA nephropathy. The first is the immune complex mediated kidney disease itself, so use treatments that tackle the immunological aspect of IgA nephropathy. The second is to focus on those general changes that occur in all kidneys when someone has lost a lot of nephrons, so those are what we would traditionally describe as supportive care measures. We want to address both of these simultaneously to try and achieve our goal of preventing kidney failure in the lifetime of our patients.
HCPLive Nephrology: What are the clinical implications of some of these recommendations you’ve described?
Barratt: I hope the implications are that we'll see more kidney biopsies, we'll see an increase in the number of people diagnosed with IgA nephropathy early, and we will be able to intervene when those patients have significant nephrons remaining and really impact on the risk of kidney failure.
The average GFR at diagnosis in the US is between 30 and 40 mils per minute, and in the UK is between about 50 and 60 mils per minute, so we are diagnosing these people far too late. We need to try and reduce the number of barriers that are in place that prevent an early diagnosis.
HCPLive Nephrology: Do you foresee any barriers potentially hindering the implementation of any of the recommendations made in this document?
Barratt: I think it's a complete change in the way we think about this disease. There are some people that we like to call “early adopters” that will buy into this message quickly, and others who've looked after IgA nephropathy for the last 30 years may feel more challenged to completely change how they view this disease, and so we are going to need to continually educate our colleagues on the data behind these recommendations. It's not opinion. It is very much driven by data, including global data from across North and South America, Europe and Asia, showing how poor outcomes are in this disease, and how we must diagnose early and intervene early.
HCPLive Nephrology: What unmet needs or unanswered questions remain that you think are most important to address moving forward?
Barratt: I think the most important one is whether we have availability of the right treatments and do we have the right treatments for the right people? IgA nephropathy is very heterogeneous, and it's likely that certain treatments will work in certain patients, and others will work in other patients. Not all treatments are going to work for everyone.
In terms of where we are, we have 2 new therapies included in the 2025 update. It's already out of date because there are 2 additional approved therapies in the United States, we're going to get another approved therapy before Christmas and another one just after Christmas, in all likelihood, and then another 2 therapies approved each year for the next 2 or 3 years.
We need to keep the document live and we need to be thinking about how we introduce all of these new therapies. Do we sequence them? Do we combine them? That is the biggest unmet need, and that is what I'm asked most often. I used to have no choice because there were no treatments, and life was easy. It wasn’t good for patients, but it was easy for me. Now I'm going to have 10 treatments, and how on earth am I going to choose between them? How do I know which one to start first? How do I know whether I can combine things safely? That's going to be the big challenge for the next 5 to 10 years.
Editors’ note: Relevant disclosures for Barratt included Argenx, Calliditas Therapeutics, Chinook Therapeutics, Galapagos NV, GSK, Novartis, Travere Therapeutics, and others.
