Advancements in CKD Management: Targeted Therapies and Emerging Paradigms
Despite incremental progress in CKD care, complement 3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) continue to challenge nephrologists with persistent proteinuria and rapid declines in eGFR, underscoring the urgent need for targeted therapies.
In this evolving landscape, pegcetacoplan has emerged as a complement-directed therapy targeting C3 dysregulation. Data from a phase II open-label study published in the New England Journal of Medicine demonstrated that pegcetacoplan reduced proteinuria by 45% and stabilized eGFR over 52 weeks in patients with C3G and IC-MPGN.
Regulatory momentum is building: pegcetacoplan is under priority review by the FDA for C3G and IC-MPGN, with a decision expected in July 2025, marking a pivotal moment in the transition from investigational use to clinical application.
The paradigm of CKD management is also shifting toward strategic combination therapies. The primary publication of the CONFIDENCE trial reported that initiating empagliflozin alongside finerenone in patients with CKD and type 2 diabetes reduced the urinary albumin-to-creatinine ratio by 32% at 24 weeks without increasing adverse events, illustrating the feasibility of simultaneous therapy initiation.
Expanding the therapeutic arsenal further, oral semaglutide has shown promise beyond glycemic control. In a retrospective cohort study published in Diabetes Care, patients initiating oral semaglutide experienced a 28% reduction in albuminuria and improvements in estimated GFR trajectories over 12 months, adding another layer to multifaceted CKD care.
These advancements are reshaping treatment algorithms by targeting specific CKD pathophysiology and leveraging drug synergies to tackle comorbidities. As nephrologists integrate these options, considerations around long-term outcomes, patient selection and sequencing of therapies will guide evolving practice patterns and inform the next generation of guideline recommendations.
Key Takeaways:
- Pegcetacoplan shows promise in stabilizing CKD progression, with regulatory review underway.
- SGLT2 inhibitors and finerenone combination therapy presents improved outcomes in CKD with type 2 diabetes.
- Oral semaglutide offers renal benefits, expanding treatment options for diabetic nephropathy.
- New treatment paradigms signal a shift towards personalized CKD management.