Finerenone and chronic kidney disease without diabetes
Finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, has been shown to slow the loss of kidney function and reduce the risk of adverse kidney and cardiovascular outcomes in people with chronic kidney disease (CKD) and type 2 diabetes. The FIND-CKD trial examined whether finerenone has similar effects in people with CKD who do not have diabetes.
In this phase 3, international, prospective, double-blind trial, 1584 adults without diabetes who had CKD (eGFR, 25 to <90 mL/min/1.73 m2) and albuminuria (uACR, 200 to ≤3500 mg/g), and who were using a renin–angiotensin system inhibitor, were randomly assigned to receive finerenone (10 to 20 mg daily) or placebo. Monitoring took place every 3 months during the first year and every 4 months until the end of the trial. Participants were treated for at least 32 months.
Overall, 1584 participants (mean age, 54.7 years; 33.8% women) underwent randomisation – 793 to receive finerenone and 791 placebo. At baseline, the mean (±SD) eGFR was 46.8±16.2 mL/min/1.73 m2 in the finerenone group and 46.6±16.0 mL/min/1.73 m2 in the placebo group.
The primary outcome of mean annual rate of change in eGFR from baseline to month 32 (total eGFR slope) was −3.3 mL/min/1.73 m2 (95% CI, −3.6 to −3.1) with finerenone and −4.0 mL/min/1.73 m2 (−4.3 to −4.8) with placebo. This represents a 0.7 mL/min/1.73 m2 (0.3 to 1.1) slower decline with finerenone (P<0.001).
Kidney or cardiovascular events (a composite of reduction from baseline of ≥57% in eGFR, kidney failure, hospitalisation for heart failure or death from cardiovascular causes) occurred in 110 participants (13.9%) in the finerenone group and 134 (16.9%) in the placebo group (HR, 0.77 [0.60 to 0.99; P=0.04]). For the composite of two kidney events, the HR was 0.78 (0.60 to 1.01; P=0.06) and for the composite of two cardiovascular events the HR was 0.60 (0.27 to 1.33).
Exploratory analyses suggested a meaningful reduction in albuminuria, with more than half of participants receiving finerenone achieving at least a 30% reduction in uACR by month 6.
The treatment was generally well tolerated. Overall and serious adverse event rates were similar between groups, and discontinuations due to adverse events were uncommon.
Hyperkalaemia, the most common adverse event, was reported in 135 participants (17.0%) receiving finerenone and 105 (13.3%) receiving placebo. Discontinuation and hospitalisation related to hyperkalaemia were infrequent, and no fatal events were reported. Rates of acute kidney injury and symptomatic hypotension were low and comparable between groups.
Overall, the trial supports finerenone as a potentially valuable addition to treatment for selected adults with non-diabetic CKD and albuminuria. The magnitude of its effect on eGFR was similar to that reported with other kidney-protective drugs, including RAS inhibitors and SGLT2 inhibitors. However, these findings apply to people with characteristics similar to the trial population and cannot be generalised. Further evidence is be needed in groups that were under-represented or excluded.
The full article can be read here.
