Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial

Abstract

Background The effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD). Methods The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily reduces risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had: (i) an estimated glomerular filtration rate (eGFR) ≥20, <45 mL/min/1.73m2; or (ii) an eGFR ≥ 45, <90 mL/min/1.73m2 with a urinary albumin: creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined: extra work for collaborating sites is kept to a minimum, and only essential information is collected. Results Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. Mean age at randomization was 63.8 (SD 13.9) years, 2192 (33%) were female, and 3570 (54%) had no prior history of DM. Mean eGFR was 37.5 (14.8) mL/min/1.73m2, including 5185 (78%) with an eGFR < 45 mL/min/1.73m2. Median (Q1-Q3) uACR was 412 (94–1190) mg/g, with a uACR < 300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease (n = 2057 [31%]), glomerular disease (n = 1669 [25%]), hypertensive/renovascular disease (n = 1445 [22%]), other (n = 808 [12%]), and unknown causes (n = 630 [10%]). Conclusions EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.

Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations

“…Notably, this cohort includes patients with glomerular disease (n ¼ 1669) and hypertensive/renovascular disease (n ¼ 1444). 58 The primary outcome of this trial was a sustained $40% decline in eGFR, ESKD, or death from renal or cardiovascular causes. The EMPA-KIDNEY trial was stopped early in March 2022 for efficacy suggesting that CKD patients without albuminuria also benefit from SGLT2 inhibitors and will soon markedly expand the population eligible for therapy.…”

Drugs in Clinical Development to Treat Autosomal Dominant Polycystic Kidney Disease

“…Conversely, a single preclinical study with a novel medicament that suggests harmful effects in experimental ADPKD can potentially lead to the unjustified exclusion of ADPKD patients from large clinical trials. Examples are the DAPA-CKD and EMPA-KIDNEY studies [ 167 , 168 ]. The DAPA-CKD found a promising attenuated rate of kidney function decline with the SGLT2 inhibitor dapagliflozin in subjects with chronic kidney disease and an elevated ACR.…”

SGLT2 Inhibitors in Chronic Kidney Disease: From Mechanisms to Clinical Practice

“…The DAPA-CKD concluded that regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with the placebo [ 115 ]. The scientific community now awaits the results of the EMPA-KIDNEY trial, which was recently reported to be “stopped early due to clear positive efficacy in people with chronic kidney disease“ [ 116 ].…”