Clinical Pearls & Morning Reports
Published January 11, 2023
The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY Collaborative Group conducted a randomized, placebo-controlled trial that evaluated the effects of treatment with empagliflozin on kidney disease and cardiovascular outcomes in a wide range of patients with chronic kidney disease (CKD). Read the NEJM Original Article here.
Q: What are the key risk factors for the development of kidney failure in patients with CKD?
A: CKD is often progressive, with a decreased glomerular filtration rate (GFR) and the presence of albuminuria representing key risk factors for the subsequent development of kidney failure. Slowing CKD progression and avoiding dialysis or kidney transplantation is highly desirable, given the effects of dialysis and kidney transplantation on quality of life and cardiovascular morbidity and mortality, as well as the substantial costs associated with kidney-replacement therapy.
Q: What gaps in our knowledge regarding the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease did this trial aim to fill?
A: There is geographic variation, but worldwide, the majority of people with CKD have low levels of albuminuria (i.e., a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of <300) and do not have diabetes. Therefore, studying a wide range of patients with CKD has particular importance for public health. The results of a prespecified subgroup analysis from a trial of the SGLT2 inhibitor dapagliflozin in patients with CKD and a urinary albumin-to-creatinine ratio of at least 200 showed that benefits with respect to kidney failure extended to patients without diabetes, but there were limited data regarding patients with an estimated GFR (eGFR) of less than 30 ml per minute per 1.73 m2 of body-surface area and how these benefits might vary among the wider population of patients with CKD.
A: In this population of patients with a wide range of GFRs, levels of albuminuria, and causes of CKD, empagliflozin led to a risk of progression of kidney disease or death from cardiovascular causes that was 28% lower than that with placebo, with no major safety concerns. 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). Treatment with empagliflozin was effective regardless of diabetes status and was effective in patients with a broad range of eGFRs, down to approximately 20 ml per minute per 1.73 m2.
A: 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.