Kidney Week 2025 Showcases Breakthrough Therapies Across Nephrology with Eight Major Trial Updates
Key Insights
Atacicept demonstrated a 45.7% reduction in proteinuria and 41.8-point placebo-adjusted advantage in the phase 3 ORIGIN 3 trial for IgA nephropathy (search), marking significant progress in targeted B-cell modulation therapy.
Finerenone achieved a 25% relative reduction in urinary albumin-to-creatinine ratio in type 1 diabetes (search) patients with chronic kidney disease (search), representing the first new therapeutic option for this population in nearly 30 years.
Fish oil supplementation reduced serious cardiovascular events by 43% in maintenance hemodialysis patients, offering a simple intervention with substantial clinical impact for this high-risk population.
American Society of Nephrology Kidney Week 2025 in Houston showcased unprecedented momentum in nephrology therapeutics, with eight major trial updates demonstrating the field's evolution from supportive care to targeted, disease-modifying interventions. The meeting highlighted advances across glomerular disease, transplant immunology, inherited kidney disorders, and cardiorenal medicine, building on a year that has already seen landmark FDA approvals in IgA nephropathy (search) and C3 glomerulopathy (search).
Atacicept Advances in IgA Nephropathy
The phase 3 ORIGIN 3 trial delivered compelling interim 36-week data for atacicept, a dual BAFF (search)/APRIL (search) inhibitor, in adults with IgA nephropathy (search). The therapy reduced urinary protein-to-creatinine ratio (UPCR) by 45.7% from baseline, yielding a 41.8-point placebo-adjusted advantage. Secondary outcomes demonstrated robust biologic and clinical effects, including a 68.3% drop in galactose-deficient IgA1 (Gd-IgA1), 81.0% hematuria resolution, and a 47.3% reduction in urinary albumin-to-creatinine ratio by week 36.
Safety data revealed greater rates of injection-site reactions but fewer serious adverse events than placebo (0.5% vs 5.1%) and no deaths. The results support atacicept's potential as a targeted, B-cell-modulating approach to IgAN, with the drug having received FDA Breakthrough Therapy Designation.
Finerenone Expands to Type 1 Diabetes
The FINE-ONE trial met its primary endpoint, with finerenone producing a 25% relative reduction in UACR over 6 months versus placebo in adults with type 1 diabetes (search) and chronic kidney disease (search) (LSGM ratio 0.75; 95% CI, 0.65 to 0.87; P = .0001). Notably, 68.1% of finerenone-treated patients achieved a ≥30% UACR reduction compared with 46.6% on placebo, aligning with ADA thresholds linked to slower kidney disease progression.
This represents a significant advance for a population with limited treatment options and no new approved therapies in nearly 30 years. The safety profile, including hyperkalemia incidence, was consistent with prior finerenone programs, with no new safety signals identified across 242 participants.
Cardiovascular Protection in Dialysis Patients
The phase 3 PISCES trial demonstrated that 4 grams of n−3 polyunsaturated fatty acids (1.6 grams EPA, 0.8 grams DHA) daily in adults on maintenance hemodialysis reduced the rate of serious cardiovascular events to 0.31 vs 0.61 per 1000 patient-days compared with placebo (Hazard Ratio [HR], 0.57, 95% CI 0.47−0.70; P < .001).
Benefits were consistent across cardiac death (HR, 0.55), myocardial infarction (HR, 0.56), stroke (HR, 0.37), peripheral vascular disease requiring amputation (HR, 0.57), and first cardiovascular event or all-cause death (HR, 0.73). Effects were observed in both patients with and without prior cardiovascular events, with similar adverse-event rates between groups and no major safety signals in the 1228-person cohort.
Novel Therapies in Rare Kidney Diseases
Setanaxib in Alport Syndrome
In a 24-week phase 2a trial of 20 patients with genetically confirmed Alport syndrome (search), setanaxib was safe and well tolerated, with adverse-event rates similar to placebo. The therapy produced a 15% mean reduction in UPCR versus placebo, with 15.4% of patients achieving ≥25% reduction and 38.5% achieving ≥10% reduction despite already optimized RAASi and SGLT2 inhibitor therapy. A 27% mean UPCR reduction persisted 4 weeks after treatment discontinuation, suggesting sustained pharmacodynamic activity.
MIL62 in Membranous Nephropathy
MIL62, a glycoengineered type II anti-CD20 (search) antibody, achieved superior complete remission rates compared to cyclosporine A in a 153-patient, 2-year randomized phase 3 trial of biopsy-proven primary membranous nephropathy (search). The therapy achieved 49.4% vs 3.9% remission at week 76 (P < .0001), with 87.5% vs 10.5% immunologic remission and a median time to complete remission of 14.1 months, which was never reached in the cyclosporine arm.
Risks of treatment failure and relapse were significantly reduced (HR, 0.04 and 0.07, respectively), alongside improvements in estimated glomerular filtration rate and quality-of-life measures. Safety was comparable between groups with no new signals.
Dual BAFF/APRIL Inhibition Strategies
Povetacicept Results
In the phase 1/2 RUBY-3 trial, povetacicept, a dual BAFF (search)/APRIL (search) inhibitor, produced substantial 48-week proteinuria reductions in both IgAN and primary membranous nephropathy (search). The therapy achieved a 64% mean UPCR reduction in IgAN (with 65% achieving <0.5 g/g and 77% declines in Gd-IgA1) and an 82% UPCR reduction with 100% immunologic remission in primary membranous nephropathy.
Hematuria resolved in 90% of IgAN patients, over half achieved clinical remission, and kidney function remained stable across cohorts. Reductions in pathogenic biomarkers were early, deep, and sustained, supporting a potential disease-modifying effect through upstream interruption of B-cell biology.
Telitacicept Phase 3 Success
In a 39-week randomized, double-blind trial, telitacicept, a BLyS (search)/APRIL (search)-targeting fusion protein, reduced 24-hour UPCR by 58.9% versus 8.8% with placebo (P <.0001), with sustained 55% reductions at week 39. Clinically meaningful proteinuria thresholds were achieved far more frequently with telitacicept, including UPCR <0.8 g/g in 61% vs 19.5%, <0.5 g/g in 42.1% vs 7.5%, and <0.3 g/g in 24.5% vs 0.6% of patients.
Kidney function remained stable, with mean estimated glomerular filtration rate essentially unchanged (−0.010 vs −0.77 mL/min/1.73 m²) and a lower risk of ≥30% eGFR decline in the telitacicept arm.
Transplant Innovation
The phase 2 BESTOW trial of 126 kidney transplant recipients demonstrated that tegoprubart achieved estimated glomerular filtration rate comparable to tacrolimus at 12 months (69 vs 66 mL/min/1.73 m²), with several subgroups showing numerically greater eGFR on tegoprubart. The composite efficacy failure rate (death, graft loss, biopsy-proven acute rejection) was 22% with tegoprubart vs 17% with tacrolimus, supporting noninferiority.
Tegoprubart demonstrated a more favorable safety profile, with markedly lower rates of new-onset diabetes (1 in 47 vs 1 in 6), tremor (1.6% vs 25%), delayed graft function (14.3% vs 25.0%), and fewer severe infections such as sepsis/bacteremia (4.8% vs 17.2%).
The meeting underscored nephrology's transformation from a field defined by limited options to one embracing mechanistic diversity and clinical ambition, with multiple pathways now targeting the underlying biology of kidney diseases rather than merely managing their consequences.