Persistent proteinuria and progressive loss of renal function in disorders like C3 glomerulopathy and immune-complex–mediated membranoproliferative glomerulonephritis represent a critical blind spot in nephrology, yet the clinical landscape is shifting with pegcetacoplan and atrasentan emerging as potent tools to curb disease progression.
Chronic proteinuria remains a pivotal driver of kidney injury, and until recently, therapeutic options for complement-mediated glomerulopathies and high-risk IgA nephropathy have been limited. Emerging agents now offer targeted strategies to address the underlying pathophysiology of these challenging conditions.
Recent insights from the phase 3 VALIANT trial show that pegcetacoplan reduces proteinuria by 68% and stabilizes eGFR over 26 weeks in patients with complement-mediated glomerulopathies.
Meanwhile, the FDA’s accelerated approval of atrasentan for IgA nephropathy provides a crucial option to reduce proteinuria in patients at high risk of progression.
While these therapies expand the nephrologist’s toolkit, their integration into practice will require careful patient selection, monitoring of response, and consideration of long-term safety. As real-world experience grows, nephrology teams will need to refine protocols for combining these agents with established treatments and to establish registries that track outcomes beyond one year.
Key Takeaways:- Pegcetacoplan reduced proteinuria and stabilized eGFR over 52 weeks in C3G and IC-MPGN patients, as shown in the VALIANT trial.
- The FDA’s accelerated approval of atrasentan offers the first targeted therapy to reduce proteinuria in high-risk IgA nephropathy.
- These innovations underscore the importance of personalized therapy selection and ongoing surveillance to optimize long-term outcomes.