Published in this week’s journal data, a distinctive design feature of the FIND-CKD trial examined finerenone across primary and secondary focal segmental glomerulosclerosis, revealing identical treatment effects regardless of underlying classification.
The FIND-CKD trial evaluated finerenone in patients with chronic kidney disease without diabetes, capturing primary versus secondary focal segmental glomerulosclerosis (FSGS) classifications directly from investigators. As HCPLive reported, this distinction was intentionally built into the protocol from the very beginning after researchers learned from the limitations of the DAPA-CKD trial. The resulting cohort split evenly, dividing 215 participants into 108 cases of primary FSGS and 107 cases of secondary FSGS.
In Plain English: The Clinical Takeaway
- Finerenone Efficacy: The medication showed consistent kidney function benefits across both primary and secondary forms of focal segmental glomerulosclerosis.
- Proteinuria Reduction: Treatment significantly increased the likelihood of reducing urine protein-to-creatinine ratios below established clinical safety thresholds by month 12.
- Treatment Sequencing: Heerspink said that determining the exact order of administering finerenone alongside SGLT2 inhibitors will require a dedicated trial.
Classification and Baseline Proteinuria in FIND-CKD
Classification relied entirely on investigator reports rather than a centralized biopsy re-review. Among the total study population, 167 participants—representing 78% of the cohort—had biopsy-proven FSGS, maintaining a similar annualized slope benefit of 1.4 mL/min/1.73 m² per year.
When asked how the population compared with other FSGS cohorts, investigator H.J. Lodewijk Heerspink described baseline proteinuria as high relative to earlier chronic kidney disease trials, though lower than levels seen in the dedicated FSGS trial known as DUPLEX. The cohort progressed quickly, with the estimated glomerular filtration rate (eGFR) in the placebo arm declining by roughly 4 to 5 mL/min/1.73 m² per year.
“The effects of finerenone in primary and secondary FSGS were identical.”
said Heerspink, noting that the published analysis found no statistical interaction by FSGS type, yielding a P value for interaction of .84.
Proteinuria Reduction Correlates with Lower Kidney Failure Risk
The research team also tested the proteinuria threshold proposed by the PARASOL initiative. Registry data from PARASOL previously demonstrated that reaching a urine protein-to-creatinine ratio (UPCR) below 0.7 g/g by 24 months correlated with an 85% lower hazard of kidney failure.
Heerspink pointed out that the finerenone group also experienced a slower eGFR decline, directly connecting proteinuria response with long-term renal outcomes.
Only about 17% of trial participants used sodium-glucose cotransporter-2 (SGLT2) inhibitors at baseline. This low utilization rate reflected enrollment beginning in 2020, prior to broad clinical recommendations for nondiabetic chronic kidney disease. While investigators did not analyze SGLT2 inhibitor use specifically within the smaller FSGS subgroup, Heerspink said that the overall trial effect remained consistent regardless of baseline SGLT2 inhibitor usage.
| Trial Parameter | FIND-CKD FSGS Cohort Data |
|---|---|
| Primary vs. Secondary Split | 108 Primary / 107 Secondary |
| Biopsy-Proven Proportion | 167 participants (78%) |
| Baseline SGLT2 Inhibitor Use | Approximately 17% |
Finerenone Shows Greater Efficacy than SGLT2 Inhibitors in FSGS
Brendon Neuen expressed surprise regarding the magnitude of the finerenone treatment effect in FSGS relative to other glomerular diseases. The effects of SGLT2 inhibitors on glomerular filtration rate in FSGS have remained modest and uncertain.
Heerspink described this as the first time a therapeutic agent has demonstrated a statistically significant and clinically important treatment effect on glomerular filtration rate decline in FSGS, exceeding outcomes observed with sparsentan or SGLT2 inhibitors. He cautioned that cross-trial comparisons remain difficult and argued that a head-to-head clinical trial would provide valuable comparative clarity.
“The right sequence and the right combination for the right patient.”
A post hoc proteomics analysis published in the Journal of the American Society of Nephrology confirmed that finerenone successfully reduced molecular markers of fibrosis, inflammation, and filtration barrier components compared with placebo.
Sequential Treatment Strategies and Future Trials
With supportive care options expanding rapidly, treating clinicians face complex choices regarding optimal drug sequencing. Questions remain over whether patients should initiate therapy with an SGLT2 inhibitor, finerenone, or combination regimens such as an endothelin receptor antagonist paired with finerenone.
Addressing these clinical dilemmas, Heerspink said that answering the question definitively requires a dedicated prospective trial. At the recent scientific summit, he presented a sequential multiple assignment randomized trial (SMART) design capable of testing initial drug selection alongside secondary and tertiary add-on agents.
References
- Heerspink HJL, Neuen BL, Agarwal R; FIND-CKD Investigators. Finerenone in chronic kidney disease without diabetes. N Engl J Med. Published online June 5, 2026. doi:10.1056/NEJMoa2604625
- Neuen BL, Perkovic V, Agarwal R, et al; FIND-CKD Investigators. Finerenone in patients with chronic kidney disease due to glomerular diseases: a randomized clinical trial. JAMA. 2026;336(3):224-235. doi:10.1001/jama.2026.9923
- Heerspink HJL, Agarwal R, Cherney D, et al. Finerenone in patients with focal segmental glomerulosclerosis. J Am Soc Nephrol. Published online November 2026. doi:10.1681/ASN.0000001333
- Rheault MN, Alpers CE, Barratt J, et al. Sparsentan versus irbesartan in focal segmental glomerulosclerosis. N Engl J Med. 2023;389(26):2436-2445. doi:10.1056/NEJMoa2308550
