Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2022 Nov 4. doi: 10.1056/NEJMoa2204233.
Abstract

BACKGROUND: The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.

METHODS: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of =40% from baseline, or death from renal causes) or death from cardiovascular causes.

RESULTS: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.

CONCLUSIONS: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).

Ratings by Clinicians (at least 3 per Specialty)
Specialty Score
Nephrology
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Internal Medicine
Cardiology
Comments from MORE raters

Cardiology rater

Important data for practitioners caring for patients with CRD.

General Internal Medicine-Primary Care(US) rater

This is very pertinent and useful, and the methods were sound. Unfortunately, cost and access continue to limit utility of the SGLT2 class of drugs.

General Internal Medicine-Primary Care(US) rater

The hazard ratio was 0.72 [0.64 to 0.82] overall for renal outcomes. The benefit tended to be more among person with diabetes and was confined to participants with an albumin/creatinine ratio > 300.

Internal Medicine rater

Another important area and group of patients who flozins benefit.

Nephrology rater

This article reinforces the current clinical practice of using flozins to slow down the progression of albuminuria kidney disease. Although in prior trials using flozins for eGFR < 30 showed benefit in a small number of patients, this trial's results confirm this benefit in a larger population with eGFR > 20ml/min.