Results of the DAPA-CKD trial and their impact on clinical practice

Abstract

Chronic kidney disease (CKD) is a growing medical and social problem in the world. Data from population base stu­dies demonstrate an increase in the prevalence of CKD and mortality. One of the causes is an increase in the number of patients with diabetes. Another reason is the limited ability to prevent the progression of the loss of kidney function. The first studies with dapagliflozin, such as DECLARE-TIMI 58 in patients with type 2 diabetes, showed a slowing of the progression of CKD to end-stage renal disease. The DAPA-CKD trial included patients with both type 2 diabetes and those without diabetes with an estimated glomerular filtration rate of 25 to 75 ml/min/1.73 m2 and albuminuria. The DAPA-CKD trial was terminated prematurely by independent monitors because of dapagliflozin overwhelming placebo. The primary endpoint, which included a sustained decrease in estimated glomerular filtration rate ≥ 50 %, end-stage renal disease, or death from renal or cardiovascular causes, was 39 % lower in the dapagliflozin group than in the placebo group. The effect of dapagliflozin on the primary endpoint was also similar among patients with dia­betic nephropathy, glomerulonephritis, ischemic or hypertensive CKD, and CKD of other or unknown cause. Also, the effect of dapagliflozin was the same regardless of concomitant cardiovascular diseases or chronic heart failure. All-cause mortality was 31 % lower among patients who received dapagliflozin at a dose of 10 mg. Dapagliflozin also significantly reduced the frequency of sudden decline in kidney function in CKD patients by 32 %. According to the results of a post-hoc analysis of the DAPA-CKD trial, compared to placebo, dapagliflozin reduced the frequency of hospitalizations due to cardiac causes, kidney and urinary tract diseases, metabolic and nutritional disorders, and oncological problems. This effect of dapagliflozin was independent of baseline type 2 diabetes. Based on the DAPA-CKD trial, dapagliflozin was approved by the Food and Drug Administration for use in reducing the risk of worsening kidney function, kidney failure, cardiovascular death, and heart failure hospitalization in adults with CKD.