Benefit of Empagliflozin in Patients with Chronic Kidney Disease – Results of the EMPA-KIDNEY Study

Methodology and Study Progress

In the international randomized double-blind placebo-controlled EMPA-KIDNEY study, adult patients with CKD with an estimated glomerular filtration rate (eGFR) of 20–45 ml/min/1.73 m² (regardless of albuminuria) and patients with an eGFR of 45–90 ml/min/1.73 m² with a urine albumin-creatinine ratio (ACR) > 200 were included. This included both diabetics and non-diabetics. Patients had to take a renin-angiotensin system inhibitor if indicated and tolerated. Patients with polycystic kidney disease or those who had undergone kidney transplantation were excluded.

Study participants were randomly divided into 2 groups. The first group received empagliflozin at a dose of 10 mg daily, while the second group received a placebo. The primary endpoint was the progression of CKD or death from cardiovascular (CV) causes. CKD progression was defined as reaching end-stage renal failure (thus being placed on dialysis or indicated for kidney transplantation), a drop in eGFR to < 10 ml/min/1.73 m², a decrease in eGFR by ≥ 40% from baseline, or death from renal causes. Secondary outcomes included the total number of hospitalizations, overall mortality, and a composite parameter encompassing heart failure hospitalizations and CV mortality.

Evaluated Patient Population

From February 2019 to April 2021, 6609 patients were randomized. Their average age was 63.8 years, 33.2% were women, and 54.0% did not have T2DM. The average baseline eGFR was 37.3 ± 14.5 ml/min/1.73 m², and 34.5% of patients had an eGFR < 30 ml/min/1.73 m². The median urinary ACR was 329, and 48.3% of study participants had an ACR ≤ 300.

Results

• After a median follow-up of 2 years, the primary endpoint occurred in 432 (13.1%) patients in the empagliflozin group and 558 (16.9%) patients in the placebo group (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.64–0.82; p < 0.001).
• The total number of hospitalizations was lower in the empagliflozin group (24.8 vs. 29.2 hospitalizations per 100 patient-years; HR 0.86; 95% CI 0.78–0.95; p = 0.003).
• No significant difference was observed in the composite parameter of heart failure hospitalizations and CV death (4.0 vs. 4.6%; HR 0.84; 95% CI 0.67–1.07; p = 0.15). The same was true for overall mortality (4.5 vs. 5.1%; HR 0.87; 95% CI 0.70–1.08; p = 0.21).
• The outcomes of empagliflozin treatment were comparable in patients with and without T2DM and were not influenced by baseline eGFR.
• In the empagliflozin group, a faster initial decline in eGFR was observed compared to the placebo group. However, this decline subsequently slowed significantly, and the long-term trend was more favorable in those treated with empagliflozin.
• The incidence of serious adverse events was comparable in both therapeutic groups.

Discussion and Conclusion

The EMPA-KIDNEY study worked with a representative sample of the population, including patients with a wide range of eGFR values, albuminuria, and causes of CKD. The results indicate that empagliflozin, compared to placebo, reduces the risk of CKD progression or death from CV causes. This medication was effective regardless of the presence of T2DM and baseline eGFR. Due to its very good tolerability, high adherence to therapy was observed, and almost all participants completed the follow-up as planned.

The beneficial effects of gliflozins on the risk of CKD progression or CV death were previously identified in several studies (e.g., the CREDENCE study on the effects of canagliflozin or the DAPA-CKD study examining the impact of dapagliflozin). EMPA-KIDNEY provided additional data confirming the beneficial effects and safety of these agents across a broad spectrum of indications.

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Source: Herrington W. G., Staplin N., Landray M. J. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2023; 388: 117–127, doi: 10.1056/NEJMoa2204233.