IgAN is the most common glomerular disease worldwide, and one of the biggest issues with regard to IgAN is that it often comes to clinical attention late. Therefore, clinicians see a spectrum of disease heterogeneity and presentations that range from patients presenting with mild disease that progresses very slowly over time to patients presenting with high-risk profiles with very inflammatory or active disease that can progress quickly. When we think about the challenges of managing IgAN and the emerging and novel treatments, we now have a better understanding and ability to prognosticate who is at risk. 

There were a number of abstracts that were presented at SCM23 that looked at this and confirmed what we already thought: that proteinuria greater than 1 g/day, along with a low estimated glomerular filtration rate (eGFR), are associated with poorer prognosis in IgAN. A systematic literature review by Lorenzi et al sought to understand the association between surrogate kidney end points and hard critical outcomes (poster 305). Researchers reported that patients with high levels of proteinuria and a low GFR are at greatest risk for progression to kidney disease in IgAN, underscoring the utility of these surrogate markers. Additionally, poster 332 by Pitcher and colleagues looked at proteinuria and disease progression and showed that the protein level was associated with poorer outcomes in IgAN. Overall, these abstracts demonstrated that the higher the level of proteinuria over time, the worse the outcomes in IgAN.

Currently, 20% to 30% of patients with IgAN are at risk of developing end-stage kidney disease within 10 to 20 years of diagnosis, so we need therapies that help us slow this progression down. A poster presented at SCM23 by Radhakrishnan et al reported the outcomes from the phase 3 PROTECT study, which looked at proteinuria reduction with combined endothelin-1a receptor and angiotensin II receptor antagonist sparsentan in IgAN (poster 333). There was a significantly greater reduction in proteinuria with sparsentan compared with the angiotensin receptor blocker irbesartan alone (ie, 50% vs 15%, respectively) among 404 patients over a 114-week period. Additionally, significantly greater complete remission rates were seen in the sparsentan group compared with the irbesartan group (21% vs 8%, respectively). These data suggest that sparsentan is better than renin-angiotensin system blockade alone for proteinuria reduction in IgAN. Long-term follow-up from this study will inform on whether the improvements seen in proteinuria translate to a better preservation of GFR in this population over that time. 

Sparsentan was recently granted US Food and Drug Administration conditional approval for IgAN. Poster 333 was a highlight for me, as it suggested that this therapy could be a potential game changer down the road, especially if it shows that the GFR is better in patients treated with sparsentan. The current standard of care in IgAN includes supportive first-line therapy with renin-angiotensin system blockade. These results might shift our supportive therapy strategy to using sparsentan plus, for example, a sodium-glucose cotransporter 2 inhibitor. 

There was also a nice poster by Lafayette and colleagues that looked at the health burden of IgAN on patients, and what they found was that quality of life was really impacted among those who had high-risk IgAN with proteinuria 1 g/day or higher and low GFR (poster 324). This reinforces the need for better and earlier treatments, as well as better biomarkers to identify the disease earlier. It also highlights the impact that glomerular diseases have on the mental health of patients, which, of course, reflects the need for improved therapies and is another important reason for us to do better with our treatment going forward.

We have definitely been learning from complement 3 glomerulopathy (C3G) as a model of complement-mediated disease, but there were not a great deal of new C3G-related data presented at SCM23; however, there were a few abstracts that were focused on FSGS. For example, long-term results for sparsentan from the large phase 2 DUET study were reported in young patients with FSGS (poster 326 by Lieberman et al) and then also in both young and adult patients with FSGS (poster 342 by Trachtman and colleagues). 

In poster 326, Lieberman et al found that young patients had a numerically lower rate of eGFR decline (based on the 2-year and all-treatment eGFR slope estimates in DUET) when compared with patients with persistent proteinuria in the FSGS clinical trial by Troost et al. The mean baseline proteinuria was approximately 4.9 g/g, and proteinuria was significantly reduced and remained reduced in patients in this long-term follow-up (240 weeks). If you look at the DUET study, which combined groups, Trachtman and colleagues reported that proteinuria improved from an average of approximately 3 g to approximately 0.8 g over the 240-week time period, suggesting sustained proteinuria reduction with the use of sparsentan in this population. 

Finally, we cannot forget about extracorporeal treatment for FSGS. While randomized controlled trials are needed to really tease out what the role is for these therapies, they have been used with some success in treatment-resistant cases of FSGS.