Breakthrough in Type 1 Diabetes Kidney Care
A groundbreaking clinical trial led by researchers at the University Health Network (UHN) in Toronto has shown promising results for finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), in slowing kidney damage for patients with type 1 diabetes and chronic kidney disease (CKD). Published in the prestigious New England Journal of Medicine (NEJM) on March 4, 2026, the FINE-ONE phase 3 trial marks a significant advancement, potentially offering the first new treatment option in decades for this vulnerable group.
Type 1 diabetes affects over 100,000 Canadians, with up to 40% developing CKD over time, leading to end-stage kidney disease in many cases. Traditional treatments like renin-angiotensin-aldosterone system (RAAS) inhibitors, such as ACE inhibitors or angiotensin-receptor blockers (ARBs), have been the standard, but residual risk remains high. Finerenone targets overactivation of mineralocorticoid receptors in the kidneys, reducing inflammation and fibrosis without the hyperkalemia risks of steroidal MRAs like spironolactone.
The trial's publication underscores UHN's leadership in cardiorenal research, affiliated with the University of Toronto, highlighting Canada's contributions to global nephrology advancements.
Understanding Finerenone and Its Mechanism
Finerenone, marketed as Kerendia, is a selective nonsteroidal MRA developed by Bayer. Unlike steroidal MRAs, it binds more specifically to mineralocorticoid receptors in the heart and kidneys, minimizing off-target effects on sex steroid receptors that cause gynecomastia or menstrual irregularities. In preclinical models, finerenone reduces proteinuria, glomerular injury, and interstitial fibrosis by blocking aldosterone-mediated pathways.
Prior to FINE-ONE, finerenone demonstrated robust efficacy in type 2 diabetes (T2D) CKD through the FIDELIO-DKD and FIGARO-DKD trials, reducing composite kidney outcomes by 18-23% and cardiovascular events. Health Canada approved Kerendia in 2022 for CKD in T2D at risk of progression, positioning it as an add-on to RAAS blockade and SGLT2 inhibitors.
For T1D patients, who face similar hyperfiltration and glomerular hypertension but lack T2D-specific therapies like SGLT2is (not yet approved for T1D in Canada), finerenone fills a critical gap. Canadian nephrologists have awaited such data, given T1D's higher CKD incidence in youth-onset cases.
The FINE-ONE Trial: Design and Methodology
The FINE-ONE trial (NCT05901831) was a multicenter, double-blind, placebo-controlled phase 3 study enrolling 242 adults aged 18+ with T1D duration ≥1 year, CKD stage 3-4 (eGFR 25 to <90 ml/min/1.73m²), and significant albuminuria (UACR 200-5000 mg/g). All participants were on stable maximum-tolerated RAAS inhibition for ≥4 weeks. Exclusion criteria included recent ketoacidosis, eGFR <25, or serum potassium >5.5 mmol/L.
Randomized 1:1 to finerenone (10 mg if eGFR ≥60 or 20 mg if <60 ml/min/1.73m², uptitrated if tolerated) or placebo for 6 months, followed by 4-week washout. Primary endpoint: relative change in UACR from baseline to month 6. Secondary: ≥30% or ≥50% UACR reductions, eGFR slope, safety (hyperkalemia, acute kidney injury).
- 119 finerenone, 121 placebo.
- Baseline UACR median: 574.6 mg/g (finerenone) vs 506.4 mg/g (placebo).
- Mean eGFR: ~45 ml/min/1.73m².
- Canadian sites: UHN Toronto General Hospital among others.
Sites spanned 15 countries, ensuring diverse representation. UHN's involvement, led by experts like Dr. David Z.I. Cherney and potentially Dr. Jacob Udell, contributed vital North American data.
Key Findings: Significant Albuminuria Reduction
Finerenone achieved a 34% UACR reduction (geometric mean ratio to baseline 0.66; 95% CI 0.60-0.73) vs 12% with placebo (0.88; 95% CI 0.79-0.98), yielding a 25% greater relative reduction (ratio 0.75; 95% CI 0.65-0.87; P<0.001). Median UACR dropped to 373.5 mg/g (finerenone) vs 475.6 mg/g (placebo).
≥30% UACR reduction: 54.3% finerenone vs 32.7% placebo; ≥50%: 28.4% vs 13.2%. eGFR declined more initially with finerenone (-5.6 vs -2.7 ml/min/1.73m²), consistent with class effect (hemodynamic), recovering post-washout. No difference in chronic slope.
| Outcome | Finerenone | Placebo | Ratio (95% CI) |
|---|---|---|---|
| UACR Change (6 mo) | -34% | -12% | 0.75 (0.65-0.87) |
| eGFR Change (6 mo) | -5.6 | -2.7 | -2.9 (-5.1 to -0.7) |
| Hyperkalemia | 10.1% | 3.3% | - |
These surrogate endpoints predict hard outcomes like kidney failure, mirroring T2D benefits.
Read full NEJM articleUHN's Pivotal Role in Canadian Research
UHN, Canada's largest research hospital and affiliated with University of Toronto, served as a key Canadian site, enrolling patients and contributing expertise in T1D nephrology. Dr. David Z.I. Cherney, a senior author and UHN nephrologist, emphasized the trial's relevance: "This is exciting for T1D patients lacking kidney-protective options beyond RAAS." UHN's Peter Munk Cardiac Centre and Toronto General Hospital sites facilitated recruitment amid Canada's high T1D prevalence (~9.5/100,000 annually).
Dr. Jacob Udell, UHN cardiologist involved in related finerenone trials (e.g., FINEARTS-HF), highlights interdisciplinary collaboration. For aspiring researchers, UHN offers research positions in cardiorenal medicine, bridging clinical trials and academia.
This NEJM publication elevates UHN's profile, attracting funding and talent to Toronto's ecosystem.
Implications for Canadian Patients and Healthcare
Canada sees ~10,000 T1D-CKD cases yearly, with dialysis costs exceeding $50,000/patient. FINE-ONE supports finerenone as adjunct therapy, potentially delaying progression by 20-30% based on T2D data. Unlike T2D, T1D CKD often strikes younger, amplifying economic burden ($1.5B annually for diabetes complications).
Health Canada may fast-track label expansion post-trial. Nephrologists via Canadian Society of Nephrology advocate integration with emerging SGLT2i approvals for T1D. Patients benefit from personalized care at centers like UHN.
Diabetes Canada GuidelinesComparing to Type 2 Diabetes Trials
- FIDELIO-DKD (2020): 18% kidney outcome reduction in T2D CKD (eGFR<60).
- FIGARO-DKD (2021): 23% in broader T2D.
- Combined: 14% CV death/KF reduction.
FINE-ONE's 25% UACR benefit aligns, despite smaller size/shorter duration. No long-term hard outcomes yet, but surrogate validates mechanism across diabetes types.
In Canada, ~3M T2D cases vs 300K T1D, but T1D CKD progresses faster.
Safety Profile and Manageable Risks
Hyperkalemia occurred in 10.1% (finerenone) vs 3.3% (placebo), mostly mild-moderate; 1.7% discontinued. Acute kidney injury similar. No gynecomastia. Monitoring potassium/eGFR recommended, as per T2D experience (15-20% hyperkalemia, low discontinuation).
For T1D, lower steroid use reduces baseline hyperkalemia risk. Canadian guidelines emphasize quarterly checks.
Future Directions and Regulatory Path
Bayer plans NDA submission for T1D CKD. Ongoing trials: CONFIDENCE (combo with SGLT2i). UHN eyes real-world studies. For researchers, opportunities in postdoc roles at UHN/Toronto focus on precision nephrology.
Canadian funding via CIHR could accelerate implementation.
Stakeholder Perspectives and Expert Quotes
Dr. Cherney (UHN): "FINE-ONE bridges a therapeutic void, with UACR as reliable predictor." Diabetes Canada: "Transformative for T1D equity."
Challenges: access/cost (~$100/month Kerendia), education for endos/nephros.
Career Opportunities in Nephrology Research
UHN's success spotlights demand for clinical researchers. Explore clinical research jobs, RA positions, or career advice. Rate profs at Rate My Professor. Canada needs 500+ nephrologists by 2030.
In summary, FINE-ONE positions finerenone as game-changer, with UHN driving Canadian innovation. Stay tuned for approvals; consult higher-ed jobs for involvement.
