Key Speakers
- Corey Cavanaugh, DO — Cleveland Clinic nephrologist
- Abdallah Geara, MD — Associate Professor of Clinical Medicine, University of Pennsylvania
- Edgar Lerma, MD — Clinical Professor of Medicine, University of Illinois Chicago
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IgAN Enters “Mechanism-First Era” Reframing Diagnosis, Treatment, and Remission
On IgAN Awareness Day, clinicians highlight earlier diagnosis, dynamic risk stratification, and emerging targeted therapies reshaping care.
IgA nephropathy (IgAN) is rapidly transitioning into what clinicians described as a “mechanism-first era,” as emerging targeted therapies reshape how nephrologists approach diagnosis, risk stratification, and long-term disease management.
To commemorate IgAN Awareness Day on May 14, 2026, HCPLive spoke with nephrologists about key evolving concepts in IgAN, including earlier diagnosis, dynamic treatment sequencing, and unresolved questions around biomarkers and remission.
“We now are in what we call a mechanism-first era,” said Edgar Lerma, MD. “We’re not in a sequencing-consensus era anymore in IgAN.”
Earlier Diagnosis Remains a Major Missed Opportunity
Despite therapeutic advances, clinicians emphasized that earlier recognition of IgAN remains one of the most important unmet needs in practice.
“The early diagnosis is, I think, the most critical,” said Corey Cavanaugh, DO. “That does not necessarily involve a new drug. It doesn’t even involve necessarily a new lab test.”
Instead, clinicians pointed to missed opportunities in routine care, particularly among younger patients presenting with microscopic hematuria, hypertension, or subtle urinary abnormalities.
“We know that 75% of patients with IgA nephropathy, when they’re biopsied, already have established CKD stage 3,” Geara said. “So early diagnosis is something we still need to work on.”
Experts also highlighted the lack of standardized screening approaches, including limited use of urinalysis in routine preventive care.
“If we can get sooner access and just basic things like urinalysis, blood pressure checks, creatinine checks in young people, we can identify a lot of this very early,” Cavanaugh added.
Risk Stratification Becomes More Dynamic and Prognostic
Clinicians described a shift away from static staging toward trajectory-based risk assessment incorporating proteinuria, eGFR slope, histology, and treatment response.
“The old model is that you have IgAN and will monitor kidney function over time,” Lerma said. “The new model is what we call an evidence-driven stratification era.”
He added that treatment response itself is now increasingly prognostic.
“How the patient responds to therapy within 12 months is becoming part of their prognosis,” Lerma said.
Proteinuria remains a central marker in clinical decision-making, despite limitations.
“The most powerful prognostic clinical indicator is proteinuria,” Cavanaugh said. “Unfortunately, it’s not a true biomarker in the sense that it tells us exactly what IgA is doing.”
A key challenge, clinicians added, is disease heterogeneity.
Expanding Treatment Options Complicate Sequencing Decisions
The IgAN treatment landscape now includes RAAS blockade, SGLT2 inhibitors, endothelin receptor antagonists, corticosteroids, targeted-release budesonide, complement inhibitors, and APRIL-directed therapies.
“The cornerstone remains ACE or ARB RAAS inhibition,” Cavanaugh said. “But endothelin receptor antagonists are the new nephron-sparing therapy that is not immunosuppression.”
He noted these agents can reduce proteinuria by approximately 50%, describing this as clinically meaningful for long-term prognosis.
Still, clinicians acknowledged there is no consensus on sequencing.
“The major question is who gets what and when,” Cavanaugh said.
“My core belief right now is nobody knows the right answer,” another clinician added. “The tools we have are inadequate to tell us exactly what to choose and when.”
Most clinicians, experts said, are still using a stepwise escalation approach rather than combination “stacking” of therapies.
Why Uptake of New Therapies Has Lagged
Despite rapid innovation, adoption of newer therapies has been slower than expected.
Lerma outlined “five buckets” driving delayed uptake: regulatory burden, skepticism about surrogate endpoints like proteinuria, infrastructure challenges, disease heterogeneity, and physician familiarity.
“Most clinicians view reduction in proteinuria as positive,” Lerma said. “But whether it translates to preventing end-stage kidney disease still has some gray area.”
Additional barriers include prior authorization requirements, REMS programs, and monitoring demands.
“Adoption usually lags evidence by around 3 to 7 years in chronic kidney disease,” Lerma said.
APRIL Inhibition and the Future of Precision Nephrology
APRIL-targeted therapies are among the most closely watched emerging treatments, designed to reduce production of galactose-deficient IgA1 earlier in the disease pathway.
“These agents target upstream B-cell activation and reduce production of galactose-deficient IgA1,” Cavanaugh said.
Lerma added that APRIL inhibition may ultimately become a foundational therapy.
“In this moment, 2026, APRIL inhibition is not an add-on yet in standard practice, but it is a future backbone candidate,” he said.
Questions remain around dual APRIL–BAFF blockade and whether broader immunologic suppression improves outcomes or increases risk.
Biomarkers and Remission Still Undefined
Despite therapeutic progress, clinicians emphasized that IgAN still lacks validated biomarkers for remission or precise response prediction.
“There’s still no definition of remission that we all agree on,” Cavanaugh said.
He added that improved therapies may ultimately force the field to define these endpoints more clearly.
“That’s the beauty of these therapies,” he said. “They force the issue of defining remission because we can actually achieve it.”
While IgAN remains incurable, clinicians expressed cautious optimism.
“There’s no cure,” Cavanaugh said. “But maybe we’re approaching that.”
Editor’s Note: Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics. Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others. Lerma reports disclosures with Amgen, Astra Zeneca, Calliditas, Novo Nordisk, Travere, Opko, and Otsuka
References
Cavanaugh C. Routine urinalysis in IgA nephropathy and young adults. HCPLive. https://www.hcplive.com/view/routine-urinalysis-iga-nephropathy-young-adults-corey-cavanaugh. Published 2026. Accessed May 15, 2026.
Geara A. Stratifying risk and optimizing therapy in IgA nephropathy. HCPLive. https://www.hcplive.com/view/stratifying-risk-optimizing-therapy-iga-nephropathy-abdallah-geara-md. Published 2026. Accessed May 15, 2026.
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