Research presented at Kidney Week 2026 highlighted the growing role of anticomplement drugs in treating IgA nephropathy (IgAN). These insights underscore the potential for precision medicine, which could eventually help clinicians match individual patient profiles to specific complement-inhibiting therapies.

Following these presentations, featured expert Ladan Zand, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Rick Davis, MD, RPh. Clinical perspectives from Dr Zand on these findings are presented here.

Currently, 2 anticomplement drugs are US Food and Drug Administration (FDA) approved for IgAN. One is iptacopan, an oral factor B inhibitor, and the other, which was approved during Kidney Week 2026, is ravulizumab, a C5 inhibitor given as an infusion.

At this year’s Kidney Week meeting, a groundbreaking abstract by Anila Cara, MD, and colleagues examined glomeruli isolated from kidney biopsy tissue by laser microdissection and analyzed by mass spectrometry to characterize IgA, IgA immune complexes, and complement in patients with IgAN (abstract TH-PO0338). Interestingly, they found little evidence of lectin pathway activation. The data revealed that C3 and C5-C9 were abundant in the IgAN biopsies, suggesting predominant activation of the alternative and terminal pathways.

During my presentation at Kidney Week 2026, I discussed how this shift in understanding will alter how we conceptualize the IgAN disease process. Choosing the right patient for the right therapy will be a major challenge for us as we work to implement a precision medicine approach. We must figure out how to match individual patient profiles to these specific drug mechanisms. One idea that we have proposed is to use mass spectrometry to identify which patients may have ongoing activity in the alternative and terminal pathways. With additional research to further validate this mass spectrometry method, we could then potentially use that information to determine which patients with IgAN might benefit from anticomplement therapy.

I would say that, in clinical practice, as it stands today, my first go-to treatments in patients with IgAN are the anti-APRIL or the anti-APRIL/anti-BAFF drugs. You should start seeing some degree of response, or a signal with respect to proteinuria and hematuria reductions, within the first 3 months of using these drugs. If you are not seeing that, then this may be the time to add anticomplement therapy.

I do want to add an important point that clinicians need to be aware of: to receive anticomplement therapy, patients should be adequately vaccinated against encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. One must be cautious about vaccine response when the patient is already on anti-APRIL or anti-APRIL/anti-BAFF therapy, which adds another layer of complexity when considering combining therapies in patients with IgAN. If anticomplement therapy is initiated, the patient should still receive their vaccines, and they may need to remain on prophylaxis against meningococcal infection for the duration of complement inhibitor therapy.

Also at Kidney Week 2026, an abstract by Xue Shen et al shared meta-analysis data for the complement inhibitors for which we have results available so far, including phase 2 trial results (abstract TH-PO0475). The results supported proteinuria reduction (placebo-adjusted change, -36%) and favorable effects on estimated glomerular filtration rate compared with placebo (mean difference, 3.1 mL/min/1.73m² per year) for these agents in patients with IgAN.

Finally, at Kidney Week 2026, there was an abstract by Dana V. Rizk, MD, and colleagues on biomarker data from the phase 3 APPLAUSE-IgAN trial of iptacopan, including data on complement biomarkers urinary sC5b-9, serum Wieslab activity, C3, and C4, as well as inflammatory biomarker urinary sCD163 (abstract FR-OR065). Ultimately, the results showed that the addition of iptacopan to supportive therapy produced an improvement in all those biomarkers except for C4, as expected based on iptacopan’s proposed mechanism of action.