Although immunoglobulin A nephropathy (IgAN) remains incurable, clinicians can now offer patients treatments that can reduce proteinuria and potentially improve outcomes.
Most recently, in February, the FDA granted accelerated approval to sparsentan (Filspari), the first non-immunosuppressive medication for treating adults with primary IgAN. In 2021, budesonide delayed-released capsules (Tarpeyo), an immunosuppressive therapy, received an FDA-approved indication for reducing proteinuria in patients with IgAN.
“For the first time, we have FDA-approved medications for the treatment of IgAN and there are clinical targets to reduce proteinuria as a means of preserving GFR [glomerular filtration rate],” said Sharon Adler, MD, Professor of Medicine at the David Geffen School of Medicine at the University of California in Los Angeles (UCLA). Dr Adler is Editor-in-Chief of Glomerular Diseases, Professor of Medicine at the David Geffen School of Medicine, and an investigator at the Lundquist Research Institute at Harbor-UCLA Medical Center, where she is a practicing nephrologist.
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‘Exciting Time to Be a Nephrologist’
Speaking at a session on IgAN management during the National Kidney Foundation’s 2023 Spring Clinical Meetings, Dr Adler said managing IgAN presents a variety of challenges, especially staying up to date with the contemporary understanding of the disease state. New and emerging treatment options are significantly changing the treatment landscape. “It is an exceptionally exciting time to be a nephrologist these days, since we have so many new and emerging treatment options for our patients,” Dr Adler said.
In addition to budesonide and sparsentan, clinicians also have in their armamentarium dapagliflozin (Farxiga), a sodium-glucose cotransport-2 (SGLT2) inhibitor originally approved in 2014 for treating type 2 diabetes but in 2021 received approval to prevent disease progression in patients with chronic kidney disease (CKD). “Since IgAN falls under the umbrella of CKD, Farxiga’s approval for CKD would extend to IgAN,” Dr Adler said. “Around 270 IgAN patients participated in the Farxiga clinical trial.”
The FDA approved budesonide based on a 9-month randomized, double-blind study in which investigators measured and evaluated participants’ urine protein-to-creatinine ratio (UPCR). Patients taking the drug had a 34% lower UPCR compared with placebo recipients, who averaged a 5% reduction. Patients prone to infections may need to avoid medication, which also may decrease immune response to some vaccines.
Sparsentan is an endothelin and angiotensin II receptor antagonist and is only available through a restricted distribution program called the FILSPARI Risk Evaluation and Mitigation Strategies (REMS). Some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure. With this agent, measuring liver aminotransferases and total bilirubin prior to initiation of treatment is required.
‘Likely to Become Game Changers’
Barry Freedman, MD, Chief of Nephrology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, said medications that specifically target IgAN are likely to become game changers for patients with this condition. “They could also prove useful in other forms of chronic kidney disease,” Dr Freedman said.
“These treatments emphasize the importance of identifying the cause of CKD, rather than just categorizing patients in CKD stages based on eGFR and albuminuria,” said nephrologist Tariq Shafi, MD, Director of the Division of Kidney Diseases, Hypertension, & Transplantation at Houston Methodist Hospital in Texas. “In a previous study, we found that nearly one-third of CKD patients had hematuria, increasing their risk of kidney function loss or dialysis.1 As IgA nephropathy can cause hematuria and effective therapies are now available, determining the cause of CKD is more crucial than ever.”
Earlier Diagnosis Important
“Clinicians in the US can take a more proactive position in diagnosing IgAN earlier in its course, so that we can treat patients earlier,” Dr Adler said. “From a research perspective, a simple diagnostic test would be a great breakthrough. Applying precision medicine principles to treatment is the next big challenge: the right drug for the right patient at the right time.”
Reference
- Orlandi PF, Fujii N, Roy J, et al. Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. BMC Nephrol. 2018 Jun 26;19(1):150. doi:10.1186/s12882-018-0951-0.
