Kidney Compass: FIND-CKD Finerenone Data in FSGS and Treatment Sequencing

Welcome back to Kidney Compass!

Recorded at the inaugural International Society of Glomerular Diseases (ISGD) Clinical Trials Summit in Galveston, Texas, this episode features hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, with guest Hiddo Heerspink, PharmD, PhD. Heerspink is a professor of clinical trials and personalized medicine at University Medical Center Groningen.

Fresh off presenting the FIND-CKD focal segmental glomerulosclerosis (FSGS) analysis at the summit, he discusses what the data mean for a disease with few proven options and how future trials should approach treatment sequencing.

How Did Finerenone Perform in FSGS in FIND-CKD?

FIND-CKD randomized 1584 adults with nondiabetic CKD to finerenone or placebo on top of maximally tolerated renin-angiotensin system blockade. Finerenone slowed annual eGFR decline by 0.7 mL/min/1.73 m² over 32 months.¹ A prespecified analysis of 903 participants with glomerular diseases included 215 with FSGS, a subgroup Heerspink described as larger than he expected.²

In the FSGS analysis published simultaneously in JASN, participants had a mean baseline eGFR of 45 mL/min/1.73 m² and a median urine protein-to-creatinine ratio (UPCR) of 1427 mg/g. Finerenone slowed total eGFR slope over 32 months by 1.3 mL/min/1.73 m² per year versus placebo (95% CI, 0.5-2.2; P = .002). The hazard ratio for the kidney composite of sustained eGFR decline of 57% or more or kidney failure was 0.58 (95% CI, 0.30-1.15). By month 12, finerenone lowered UPCR by 41% versus placebo (95% CI, 26%-53%). Hyperkalemia-related adverse events occurred in 15% of the finerenone group and 20% of the placebo group.³

A distinguishing design feature was the collection of primary versus secondary FSGS classification from investigators. Heerspink said his team learned from DAPA-CKD, which did not capture this distinction, and built it into FIND-CKD from the start. Classification relied on investigator report rather than biopsy re-review, and the split was nearly even, with 108 participants classified as primary FSGS and 107 as secondary.

“The effects of finerenone in primary and secondary FSGS were identical,” Heerspink said, and the published analysis found no interaction by FSGS type (P for interaction = .84). Among the 167 participants (78%) with biopsy-proven FSGS, the slope benefit was similar at 1.4 mL/min/1.73 m² per year.³

Wadhwani asked how the population compared with other FSGS cohorts. Heerspink described baseline proteinuria as high relative to FSGS subgroups in earlier CKD trials, though lower than in DUPLEX, the dedicated FSGS trial. The cohort progressed quickly, with eGFR in the placebo arm declining by roughly 4 to 5 mL/min/1.73 m² per year.

The team also tested the proteinuria threshold proposed by the PARASOL initiative. In PARASOL registry data, reaching a UPCR below 0.7 g/g by 24 months was associated with an 85% lower hazard of kidney failure.⁴ In FIND-CKD, which measured UPCR in first morning void samples, finerenone increased the odds of reaching UPCR below 700 mg/g at month 12 (odds ratio, 6.8; 95% CI, 3.0-17.2).³ Heerspink noted the finerenone group also had slower eGFR decline, connecting proteinuria response with eGFR outcomes.

Only about 17% of participants used SGLT2 inhibitors at baseline, reflecting enrollment beginning in 2020 before broad recommendations for nondiabetic CKD. Heerspink noted the team did not analyze SGLT2 inhibitor use within the FSGS subgroup given small numbers. In the overall trial, however, the effect of finerenone was consistent regardless of SGLT2 inhibitor use, and he expects the same holds in FSGS.

How Does the Effect Compare With Other FSGS Therapies?

Neuen said he was surprised by the size of the treatment effect in FSGS relative to other glomerular diseases. Effects of SGLT2 inhibitors on GFR in FSGS have been modest and uncertain. In DUPLEX, sparsentan reduced proteinuria more than irbesartan, but the trial showed no significant difference in eGFR slope at 108 weeks.⁵

Heerspink called this the first time a drug has shown a statistically significant and “clinically important treatment effect on GFR decline” in FSGS, exceeding what was seen with sparsentan or SGLT2 inhibitors. He cautioned cross-trial comparisons are difficult and a head-to-head trial would be valuable. He also pointed to a mechanistic rationale, citing animal data showing inhibition of aldosterone overactivation can protect the podocyte, a central target in FSGS pathophysiology. In a post hoc proteomics analysis, finerenone reduced markers of fibrosis, inflammation, and filtration barrier components versus placebo.³

What Treatment Should Come First in FSGS?

With supportive care options expanding, Wadhwani asked whether patients should start with an SGLT2 inhibitor, finerenone, or a combination such as an endothelin receptor antagonist plus finerenone. Heerspink said the question requires a dedicated trial. At the summit, he presented a sequential multiple assignment randomized trial (SMART) design, which can test which drug to start with and which agents to add second or third. These designs, he said, allow investigators to test “the right sequence and the right combination for the right patient.”

References:

1. 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

2. 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

3. 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

4. RaDaR validation confirms PARASOL findings on FSGS surrogate endpoint, with Daniel Gale, PhD, MB BChir. HCPLive. Published June 7, 2025. Accessed November 15, 2026. https://www.hcplive.com/view/radar-validation-confirms-parasol-findings-on-fsgs-surrogate-endpoint

5. 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