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An investigational anti-mineralocorticoid agent slowed chronic kidney disease (CKD) progression in people with type 2 diabetes, the showed.

In the trial, 17.8% of the 2,833 patients on finerenone experienced a primary outcome event -- kidney failure, a sustained decrease of at least 40% in eGFR from baseline, and death from renal causes -- versus 21.1% of the 2,841 on placebo (hazard ratio 0.82, 95% CI 0.73-0.93, P=0.001), reported George Bakris, MD, of the University of Chicago, and colleagues.

Those on finerenone also had a reduced risk of experiencing a key secondary cardiovascular outcome -- death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure -- compared with those on placebo (13% vs 14.8%, respectively; HR 0.86, 95% CI 0.75-0.99, P=0.03).

Incidence rates for all individual cardiovascular outcomes were lower among those on finerenone, except for nonfatal stroke, which was similar between the two groups.

These findings were presented at the American Society of Nephrology's virtual Kidney Week and simultaneously published in the .

"This is an exciting discovery because we have had many other failed discoveries in this high-risk population of diabetes and chronic kidney disease," co-author Rajiv Agarwal, MD, of Indiana University in Indianapolis, explained during a press conference.

Acting as a nonsteroidal, selective mineralocorticoid receptor antagonist, the researchers pointed out that finerenone has previously shown the ability to reduce the urinary albumin-to-creatinine ratio in patients with CKD also treated with a RAS blocker, but has demonstrated less of an impact on serum potassium levels than spironolactone (Aldactone) -- a steroidal, nonselective inhibitor of the mineralocorticoid receptor -- as seen in Agarwal's 2019 AMBER trial.

Despite this, 2.3% of patients on finerenone discontinued treatment during the current trial due to hyperkalemia versus 0.9% of those on placebo. Over 18% of people on finerenone experienced a hyperkalemia-related adverse event versus 9% of those on placebo, but there were no fatal hyperkalemia events reported.

However, putting this into perspective, Agarwal underscored that this 2.3% discontinuation rate (over a median follow-up of 2.6 years) is far lower than the 23% discontinuation rate due to hyperkalemia (over 12 weeks) seen in the AMBER trial of patients on spironolactone alone without adjunctive patiromer (Veltassa).

"An ideal drug would cause no hyperkalemia," Agarwal stated. "But if you look at the absolute risk, it's a fraction of what we saw when we used spironolactone in this vulnerable population."

The double-blind trial included adults with confirmed CKD with a urinary albumin-to-creatinine ratio between 30 to <300, as well as an eGFR between 25 to <60 mL/min/1.73 m², plus a history of diabetic retinopathy. Patients were also included if they had a severely elevated albuminuria -- a urinary albumin-to-creatinine ratio between 300 to 5,000 -- and an eGFR of 25 to <75 mL/min/1.73 m².

All participants also had a serum potassium level of 4.8 mmol/L or less prior to study entry and were also treated with an ACE inhibitor or angiotensin receptor blocker at the maximum dose.

Among the half assigned to finerenone, those with an eGFR of 25 to <60 mL/min/1.73 m² at the screening visit received an initial dose of 10 mg once daily, while those with an eGFR of 60 mL/min/1.73 m² or higher received an initial dose of 20 mg once daily. After a month of treatment, it was encouraged to increase the once daily dose from 10 mg up to 20 mg if serum potassium levels and eGFR were stable.

As for other secondary outcomes, death from any cause and hospitalization for any cause were not significantly different between the two groups.

In an , NEJM associate editor Clifford Rosen, MD, and deputy editor Julie Ingelfinger, MD, pointed out that this benefit on CKD progression didn't quite match the SGLT-2 inhibitor canagliflozin (Invokana) in the 2019 CREDENCE trial.

"One explanation for the different findings in the two trials, as noted by Bakris et al., is the fact that SGLT2 inhibitors were allowed in the present trial, whereas patients treated with mineralocorticoid receptor antagonists were excluded from the CREDENCE trial," Rosen and Ingelfinger noted, as less than 5% of the total cohort in this study were on an SGLT-2 inhibitor at baseline.