About FIND-CKD
Trial overview
FIND-CKD was a multicenter, randomized, double-blind, placebo-controlled phase 3 trial testing whether finerenone, a non-steroidal mineralocorticoid receptor antagonist, could slow the progression of chronic kidney disease (CKD) in adults who do not have diabetes. The trial enrolled 1,584 participants at 283 sites across 24 countries.
Finerenone has previously been shown to reduce kidney disease progression and cardiovascular events in people with CKD associated with type 2 diabetes, based on the earlier FIDELIO-DKD and FIGARO-DKD trials. FIND-CKD was designed to test whether the same drug could benefit the larger group of people whose kidney disease has a different cause: most people living with CKD worldwide do not have diabetes, yet they have had comparatively few dedicated treatment trials and few proven therapeutic options.
Why the trial was needed
Chronic kidney disease affects an estimated 800 million people worldwide and is a leading cause of death and disability. Overactivation of the mineralocorticoid receptor is thought to contribute to inflammation and fibrosis in the kidney and cardiovascular system across many forms of kidney disease, not only diabetic kidney disease. Because finerenone had already been shown to slow kidney function decline and reduce cardiovascular events in people with type 2 diabetes and CKD, the FIND-CKD investigators set out to determine whether the same mechanism could be harnessed in non-diabetic CKD, where the causes are more varied and include hypertensive or ischaemic nephropathy and a range of glomerular diseases such as IgA nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy.
Trial design
Adults were eligible if they had non-diabetic CKD with an estimated glomerular filtration rate (eGFR) of 25 to under 90 mL/min/1.73m² and albuminuria (a urinary albumin-to-creatinine ratio of 200 to 3,500 mg/g), and were already taking a renin–angiotensin system inhibitor (an ACE inhibitor or angiotensin receptor blocker) at the maximum dose they could tolerate. People with autosomal dominant or recessive polycystic kidney disease, lupus nephritis, or ANCA-associated vasculitis were excluded. In the trial population, kidney disease was attributed to hypertensive or ischaemic nephropathy in around 29% of participants and to chronic glomerulonephritis in around 57%, with the remainder classified as another or unknown cause.
Participants were randomly assigned 1:1 to receive finerenone (10 or 20 mg once daily, with the starting dose set according to eGFR) or matching placebo, in addition to their background standard of care. The primary outcome was the total eGFR slope: the mean annual rate of change in eGFR from baseline to month 32, a validated surrogate endpoint for CKD progression. Secondary outcomes included a composite of kidney and cardiovascular events (a sustained eGFR decline of at least 57%, kidney failure, hospitalization for heart failure, or death from cardiovascular causes), along with separate kidney-only and cardiovascular-only composites.
What the trial showed
Over 32 months, eGFR declined more slowly with finerenone than with placebo: the total eGFR slope was −3.3 mL/min/1.73m² per year with finerenone compared with −4.0 mL/min/1.73m² per year with placebo, a between-group difference of 0.7 mL/min/1.73m² per year (95% CI, 0.3 to 1.1; P<0.001). Finerenone also reduced the risk of the key secondary composite outcome of kidney or cardiovascular events by 23% relative to placebo (hazard ratio, 0.77; 95% CI, 0.60 to 0.99; P=0.043).
The safety profile was consistent with finerenone's established profile in earlier trials. Overall adverse events (68.3% vs 65.4%) and serious adverse events (20.9% vs 21.2%) were similar between groups. As expected for a mineralocorticoid receptor antagonist, hyperkalemia was the most common adverse event and occurred more often with finerenone than placebo (17.0% vs 13.3% of participants). It infrequently led to discontinuation of treatment (1.5% vs 0.1%) or hospitalization (0.9% vs 0.6%), and no participant in either group died as a result.
Interpretation
FIND-CKD demonstrates that finerenone slows the rate of eGFR decline in adults with non-diabetic CKD, extending previous findings in diabetic kidney disease. Because most people living with CKD worldwide do not have diabetes, these results suggests that many more additional individuals with CKD may benefit from treatment with finerenone.
