Finerenone Slows CKD Advance in Diabetics

Investigational drug also decreased the risk of major cardiovascular events, a study found

BY JODY A. CHARNOW FINERENONE, an investigational mineralocorticoid receptor antagonist (MRA), slows progression of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus compared with placebo, according to phase 3 trial results.

“This is great news for people with type 2 diabetes and CKD,” said study investigator Rajiv Agarwal, MD, MS, professor of medicine at Indiana University in Indianapolis, who presented study findings at the conference. “They now have another option to protect their heart and their kidneys through finerenone.”

Finerenone is a selective nonsteroidal MRA. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) trial, the drug, when added to the maximum tolerated dose of guideline-directed therapy, was associated with an 18% decreased risk of a composite endpoint HOSPITALIZED patients with serum sodium levels outside of the optimal range when they are discharged are at increased risk of dying within 1 year, investigators reported.

Hypernatremia at hospital discharge more strongly influenced 1-year mortality than hyponatremia at discharge.

In a single-center study of 59,901 hospitalized patients, a team led by Charat Thongprayoon, MD, of Mayo Clinic in Rochester, Minnesota, found that 1-year mortality rates were 26.1%, 15.5%, 11.6%, 17.2%, and 49.4% for CHRONIC KIDNEY disease (CKD) is associated with new-onset dyslipidemia, according to investigators.

Using the Japanese Specific Health Check and Guidance System, Takaaki Kosugi, MD, of Nara Medical University in Kashihara, Nara, Japan, and colleagues identified 51,009 patients with of time to kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) of 40% or more from baseline over a period of at least 4 weeks, or renal death compared with placebo over a median follow-up duration of 2.6 years. According to investigators, 29 patients would need to be treated to prevent a primary composite endpoint event at 36 weeks, which Dr Agarwal said “would be considered pretty good.”

In addition, finerenone treatment was significantly associated with a 14% decreased risk of a key secondary endpoint — a composite of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure — compared with placebo over a median follow-up of 2.6 years.

The FIDELIO-DKD trial is the first large contemporary positive outcomes study in patients with both CKD and type 2 diabetes mellitus with a primary patients with serum sodium values of 132 or less, 133-137, 138-142, 143-147, and 148 mEq/L or higher, respectively. Compared with a reference value of 138-142 mEq/L, those with values of 132 or less, 133-137, 143-147, and 148 mEq/L or higher had significantly increased odds of 1-year mortality by a factor of 1.43, 1.10, 1.35, and 3.86 (all P values less than or equal to .001), respectively, after adjustment for age, sex, race, admission serum sodium values, Charlson comorbidity score, and other potential confounders, according to the investigators. CKD and 254,884 without CKD who at baseline were free of dyslipidemia, which is a significant risk factor for cardiovascular disease. Over a median 3.1 years, 14.8%, 17.0%, and 4.3% of individuals experienced high levels of triglycerides (150 mg/dL or greater) and low-density lipoprotein (LDL; 140 mg/dL or greater) composite endpoint exclusively consisting of kidney-specific outcomes, according to a press release from Bayer, the pharmaceutical company developing the drug. Investigators randomly assigned 5734 patients to receive finerenone or placebo. Enrollment criteria

Researchers report an 18% decreased risk of deteriorating kidney function.

include an eGFR (in mL/min/1.73 m2) of 25 or higher but less than 75 and a urinary albumin-to-creatinine ratio of 30 to 5000 mg/g.

Patients in both study arms received standard of care, including glucoselowering medications and maximum tolerated doses of drugs that block the renin-angiotensin system such as

“The optimal range of serum sodium at hospital discharge was 138 to 142 mEq/L, but almost half of hospitalized patients were discharged with serum sodium outside of this optimal range,” Dr Thongprayoon told Renal & Urology News. “Targeting serum sodium to the optimal range before hospital discharge may potentially lead to more favorable long-term survival.”

The study population was 54% male and 93% White. Discharge serum sodium values were the last measurements within 48 hours before discharge. ■ and low levels of high-density lipoprotein (HDL; less than 40 mg/dL), respectively.

After adjusting for potential confounders, patients with CKD had significant 10% and 16% greater risks for high triglycerides and low HDL, respectively, but no elevated risk for high LDL, compared with patients who did not have CKD. ■ angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).

Dr Agarwal noted that nearly 90% of the patients in FIDELIO-DKD had macroalbuminuria and more than half had an eGFR less than 45. If results of the sister study FIGARO-DKD (Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease) — in which approximately half of the patients have microalbuminuria and a mean eGFR of 68 — are also positive “the impact of finerenone will be even more broadly felt. It may then be used by most patients with type 2 diabetes and CKD.” Results of FIGARODKD are expected in 2021, he said.

He cautioned that finerenone use requires close monitoring of serum potassium levels, “much like we do currently with ACE inhibitors and ARBs.”

Study findings were published concurrently in the New England Journal of

Sodium Abnormalities Up Mortality

New-Onset Dyslipidemia Associated With CKD

Medicine. ■

AKI Worsens Outcomes in Flu Patients

PATIENTS HOSPITALIZED with influenza who develop acute kidney injury (AKI) experience worse morbidity and mortality than their counterparts without AKI, investigators reported.

Among 120,730 influenza hospitalizations in a National Inpatient Sample (2012 to 2014), 16,270 (13.5%) were complicated with AKI. In adjusted analyses, patients with AKI had 3.8-, 8.7-, 9.5-, 3.0-, and 5.6-fold increased odds for mortality, severe sepsis, septic shock, rhabdomyolysis, and intubation, respectively, compared with patients without AKI, Nasha Elavia, MD, of the Wright Center for Graduate Medical Education in Scranton, Pennsylvania, and colleagues reported. Patients with AKI also had a significant 1.8-day longer length of stay. ■