Nephrology saw notable regulatory and clinical progress in 2025, with US Food and Drug Administration (FDA) approvals and late-stage trial results expanding treatment options across chronic kidney disease (CKD), IgA nephropathy (IgAN), lupus nephritis, and C3 glomerulopathy (C3G). These developments reinforced nephrology as a rapidly evolving therapeutic field, with growing integration of precision-driven, mechanism-based therapies.

IgAN dominated the headlines, reflecting a shift from supportive care to targeted, disease-modifying strategies. The FDA’s accelerated approval of atrasentan confirmed acceptance of proteinuria-based endpoints, while phase 3 data for telitacicept and sibeprenlimab, alongside interim ORIGIN-3 results for atacicept, highlighted multiple mechanisms, including endothelin A receptor antagonism and BAFF/APRIL inhibition. These advances signal a move toward therapy tailored to disease biology rather than uniform immunosuppression

Complement-targeted therapy matured in rare glomerular disease with FDA approval of pegcetacoplan for C3G and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), marking a durable treatment option and advancing precision nephrology, particularly for post-transplant recurrence. In parallel, transplant innovation progressed as FDA clearance of gene-edited kidney xenotransplant trials moved from concept to early clinical reality, representing a translational step toward addressing organ shortages.

Beyond immune-mediated disease, combination therapy gained traction in CKD with type 2 diabetes. The CONFIDENCE trial showed early, simultaneous initiation of finerenone and SGLT2 inhibitors was safe and effective, supporting a proactive approach rather than stepwise escalation.

Taken together, 2025 was pivotal for nephrology, advancing precision-driven, mechanism-based care, supported by regulatory momentum, late-stage trial success, and increasing cardiometabolic integration. Read below for a year in review of HCPLive’s editorial coverage.

FDA News

FDA Approves Semaglutide (Ozempic) for Type 2 Diabetes, Chronic Kidney Disease

The FDA approved semaglutide (Ozempic) to reduce the risk of kidney disease worsening, end-stage kidney disease (ESKD), and cardiovascular death in adults with type 2 diabetes and CKD. The decision was supported by the phase 3b FLOW trial, which demonstrated a 24% relative risk reduction compared with placebo when added to standard therapy.

Semaglutide’s approval reinforces cardio-renal integration, positioning endocrinology and nephrology as co-stewards of CKD progression prevention.

FDA Clears First Xenotransplant Trial for Gene-Edited Kidneys

On February 3, 2025, the FDA cleared United Therapeutics’ IND application to study UKidney™, derived from a 10 gene-edited source pig. The EXPAND trial began in November 2025 at NYU Langone Health with an initial 6-patient cohort, expanding to 50 participants to support a future Biologics License Application. This milestone represents a translational step toward expanding transplant options and may alleviate organ shortages for patients with ESKD.

Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy

The FDA granted accelerated approval to atrasentan on April 2, 2025, as the first selective endothelin A receptor antagonist approved to reduce proteinuria in adults with primary IgAN at risk of rapid progression. Approval did not require a REMS, reflecting regulatory confidence in proteinuria as a surrogate endpoint. This decision may broaden targeted therapy use in IgAN and reinforce proteinuria as a valid endpoint for future drug development.

FDA Approves Belimumab (Benlysta) Autoinjector for Pediatric Lupus Nephritis

On June 24, 2025, the FDA approved a 200 mg/mL autoinjector of belimumab for children ≥5 years with active lupus nephritis, complementing the existing approval for pediatric systemic lupus erythematosus. This subcutaneous option allows at-home administration, which may increase adherence and reduce clinic visits, improving real-world disease management for pediatric patients.

FDA Approves Pegcetacoplan (Empaveli) for C3 Glomerulopathy, IC-MPGN

Pegcetacoplan was approved on July 28, 2025, for adolescents and adults with C3G or IC-MPGN, including post-transplant recurrence. Approval followed positive 26-week VALIANT trial results, the largest single trial in these rare diseases. This marks a durable, precision-focused treatment strategy that may shift management of complement-mediated glomerular diseases and improve outcomes in high-risk or post-transplant patients.

Related: VALIANT: Pegcetacoplan Shows Sustained Efficacy in C3G and IC-MPGN, With Carla Nester, MD

Trial Updates and New Guidelines

CONFIDENCE: SGLT2i and Finerenone Effective, Safe to Initiate Simultaneously in CKD

CONFIDENCE showed simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) was well-tolerated and produced greater reductions in UACR than either drug alone in CKD with type 2 diabetes. These findings support early, proactive combination therapy, which could redefine standard CKD care by emphasizing simultaneous cardiometabolic intervention.

Telitacicept Achieves Primary Endpoint in IgA Nephropathy Phase 3 Study

Telitacicept, a B-cell modulating biologic, achieved a -58.9% change in 24-hour urine protein-to-creatinine ratio versus -8.8% for placebo, with a favorable safety profile. These results highlight the potential of telitacicept to provide a targeted, disease-modifying approach in IgAN, moving treatment away from uniform immunosuppression.

Understanding Atacicept & 36-Week ORIGIN 3 Data from Kidney Week 2025, With Jonathan Barratt, MBChB, PhD

Interim results showed atacicept, a dual BAFF/APRIL inhibitor, reduced Gd-IgA1 by 68.3%, resolved dipstick hematuria in 81% of patients, and reduced UACR by 47.3%. Jonathan Barratt, MBChB, PhD, explained that atacicept may reshape IgAN management by providing a precision approach that addresses underlying pathogenic mechanisms.

BESTOW: Tegoprubart Showcases Safer Prevention of Kidney Transplant Rejection Over Tacrolimus

Phase 2 BESTOW data suggest tegoprubart provides comparable eGFR improvements to tacrolimus but with a superior safety profile, including fewer metabolic and neurologic adverse events. These findings support further evaluation of calcineurin inhibitor–sparing regimens, which could improve long-term graft survival and patient quality of life.

Sibeprenlimab Halves Proteinuria in IgAN in Phase 3 VISIONARY Trial

Interim analysis showed sibeprenlimab reduced proteinuria by 51.2% at 9 months versus placebo. FDA BLA acceptance in May anticipates a potential approval by November 28, 2025. This therapy introduces APRIL-targeted treatment for IgAN, potentially expanding options for patients who may not respond to traditional immunomodulation.

Feature Content/Podcasts

Kidney Compass: Understanding Renal Outcomes in SURPASS-CVOT

Host Brendon Neuen, MBBS, PhD, and Sophia Zoungas, MBBS, PhD, discussed a post hoc analysis of the SURPASS-CVOT trial, showing tirzepatide (Mounjaro) slowed kidney function decline and reduced albuminuria progression compared with dulaglutide (Trulicity) in patients with type 2 diabetes, ASCVD, and high-risk CKD. These findings may guide therapy selection toward agents that confer dual metabolic and renal benefit.

HCPLive Five at European Renal Association (ERA) Congress 2025

Coverage highlighted discussions on pegcetacoplan in C3G and IC-MPGN, 3 IgAN therapies in development, and early combination therapy with finerenone and empagliflozin. These conversations emphasize how emerging therapies and proactive management strategies may influence real-world CKD care and clinical decision-making.

Kidney Compass: The Future of Cardiovascular-Kidney-Metabolic Trial Design

Host Neuen and Shikha Wadhwani, MD, MS, alongside guests Richard Pratley, MD, medical director at the Advent Health Diabetes Institute, and Muthiah Vaduganathan, MD, MPH, codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, explored strategies to improve trial infrastructure, patient engagement, and evidence generation. This discussion underscores the importance of designing trials that more closely reflect complex, multi-system patient populations in CKD and cardiovascular disease.

Kidney Compass: NUDGE-CKD and the Power of Pragmatic Trials

In this episode of Kidney Compass, Neuen, alongside Tor Biering-Sørensen, MD, MPH, PhD, and Kristoffer Skaarup, MD, discussed the landmark NUDGE-CKD trial, a pragmatic study aimed at improving guideline-based CKD care. This pragmatic approach highlights how evidence generation in real-world settings can inform broader implementation strategies for CKD management.

Kidney Compass: Applying Hierarchical Composite Endpoints in Kidney Disease Trials

In this episode of Kidney Compass, Neuen and Shikha Wadhwani, alongside guests Dustin Little, MD, and Niels Jongs, PhD, examined hierarchical composite endpoints (HCEs) in rare and complex kidney disease trials, emphasizing their potential to optimize trial efficiency, improve data interpretation, and advance therapy development. Adoption of HCEs could accelerate regulatory approval of novel therapies in CKD and rare glomerular diseases.

References

1. Brooks A. FDA Approves Semaglutide (Ozempic) for Type 2 Diabetes, Chronic Kidney Disease. HCPLive. January 28, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-ozempic-type-2-diabetes-chronic-kidney-disease. Accessed December 24, 2025.

2. Brooks A. FDA Clears First Xenotransplant Trial for Gene‑Edited Kidneys. HCPLive. February 3, 2025. https://www.hcplive.com/view/fda-clears-first-xenotransplant-trial-gene-edited-kidneys. Accessed December 24, 2025.

3. Campbell P. Atrasentan (Vanrafia) Receives Accelerated Approval in IgA Nephropathy. HCPLive. April 3, 2025. https://www.hcplive.com/view/atrasentan-vanrafia-receives-accelerated-approval-in-igan. Accessed December 24, 2025.

4. Brooks A. FDA Approves Belimumab (Benlysta) Autoinjector for Pediatric Lupus Nephritis. HCPLive. June 24, 2025. https://www.hcplive.com/view/fda-approves-belimumab-benlysta-autoinjector-for-pediatric-lupus-nephritis. Accessed December 24, 2025.

5. Brooks A. FDA Approves Pegcetacoplan (Empaveli) for C3 Glomerulopathy, IC‑MPGN. HCPLive. July 28, 2025. https://www.hcplive.com/view/fda-approves-pegcetacoplan-empaveli-for-c3-glomerulopathy-ic-mpgn. Accessed December 24, 2025.

6. Campbell P. CONFIDENCE: SGLT2i and Finerenone Effective, Safe to Initiate Simultaneously in CKD. HCPLive. June 5, 2025. https://www.hcplive.com/view/confidence-sglt2i-and-finerenone-effective-safe-to-initiate-simultaneously-in-ckd. Accessed December 24, 2025.

7. Barratt J, MBChB, PhD, FRCP. Understanding Atacicept & 36‑Week ORIGIN 3 Data from Kidney Week 2025. HCPLive. November 6, 2025. https://www.hcplive.com/view/atacicept-36-week-origin-3-data-kidney-week-2025-jonathan-barratt-mbchb-phd. Accessed December 24, 2025.

8. Hillenbrand A. Telitacicept Achieves Primary Endpoint in IgA Nephropathy Phase 3 Study. HCPLive. November 18, 2025. https://www.hcplive.com/view/telitacicept-achieves-primary-endpoint-iga-nephropathy-phase-3-study. Accessed December 24, 2025.

9. Johnson, V. BESTOW: Tegoprubart Showcases Safer Prevention of Kidney Transplant Rejection Over Tacrolimus. HCPLive. 2025. https://www.hcplive.com/view/bestow-tegoprubart-showcases-safer-prevention-kidney-transplant-rejection-over-tacrolimus. Accessed December 24, 2025.

10. Cambpell, P. ERA 2025: Sibeprenlimab Halves Proteinuria in IgAN in Phase 3 VISIONARY Trial. HCPLive. 2025. https://www.hcplive.com/view/era-2025-sibeprenlimab-halves-proteinuria-in-igan-in-phase-3-visionary-trial. Accessed December 24, 2025.

11. Neun, B, Wadhwani, S.. Kidney Compass: Understanding Renal Outcomes in SURPASS‑CVOT. HCPLive. 2025. https://www.hcplive.com/view/kidney-compass-renal-outcomes-in-surpass-cvot-sophia-zoungas. Accessed December 24, 2025.

12. Neun, B, Wadhwani, S. HCPLive Five at European Renal Association (ERA) Congress 2025. HCPLive. 2025. https://www.hcplive.com/view/hcplive-five-at-european-renal-association-era-congress-2025. Accessed December 24, 2025.

13. Neun, B, Wadhwani, S.. Kidney Compass: The Future of Cardiovascular‑Kidney‑Metabolic Trial Design. HCPLive. 2025. https://www.hcplive.com/view/kidney-compass-the-future-cardiovascular-kidney-metabolic-trial-design. Accessed December 24, 2025.

14. Neun, B, Wadhwani, S.. Kidney Compass: NUDGE‑CKD and the Power of Pragmatic Trials. HCPLive. 2025. https://www.hcplive.com/view/kidney-compass-nudge-ckd-the-power-pragmatic-trials. Accessed December 24, 2025.

15. Neun, B, Wadhwani, S.. Kidney Compass: Applying Hierarchical Composite Endpoints in Kidney Disease Trials. HCPLive. 2025. https://www.hcplive.com/view/kidney-compass-applying-hierarchical-composite-endpoints-kidney-disease-trials. Accessed December 24, 2025.