Kidney Week: Dapagliflozin Renoprotective, Cardioprotective in CKD Patients

Dapagliflozin was found to be renoprotective and cardioprotective in patients with most causes of chronic kidney disease (CKD) with or without type 2 diabetes, according to a secondary analysis of the DAPA-CKD trial presented at the American Society of Nephrology’s virtual Kidney Week, held October 19-25, 2020.

"As we've already seen from this study in patients with chronic kidney disease with and without type 2 diabetes, dapagliflozin reduced the risk of kidney failure, reduced the risk of death from cardiovascular causes or hospitalization for heart failure, and prolonged survival,” said lead author David Wheeler, MD, George Institute for Global Health, Sydney, Australia, during the virtual presentation. "In this pre-specified analysis, we've shown that these renal-cardiovascular mortality benefits are present regardless of the underlying cause of chronic kidney disease and regardless of the presence or absence of type 2 diabetes."

Wheeler and colleagues re-examined the 4304 CKD patients from the original trial, who had an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m² and a urine albumin-to-creatinine ratio of 200-5000 mg/g.

The patients were randomized to receive 10 mg of dapagliflozin once daily or placebo and the primary outcome was a composite of sustained decline in eGFR of ≥50%, end-stage kidney disease, or death from cardiovascular or kidney causes.

The results showed that patients treated with dapagliflozin had a significantly reduced risk for the primary endpoint regardless of the underlying cause of kidney disease (hazard ratio [HR] 0.61, 95% CI 0.51-0.72).

Furthermore, when broken down by etiology of kidney disease, dapagliflozin significantly reduced the risk for the primary endpoint in patients whose kidney disease was caused by diabetic nephropathy (HR 0.63, 95% CI 0.51-0.78) and glomerulonephritides (HR 0.43, 95% CI 0.26-0.71) vs placebo.

However, patients whose kidney disease was caused by ischemic/hypertensive CKD (HR 0.75, 95% CI 0.44-1.26) or caused by other or unknown causes (HR 0.58, 95% CI 0.29-1.19) didn't see a significant benefit with dapagliflozin.

In an additional analysis of 270 patients with IgA nephropathy, there was a 71% reduced risk for this primary endpoint with dapagliflozin vs placebo over a 32-month follow-up period (HR 0.29, 95% CI 0.12-0.73).

One limitation to this study was the exclusion of patients with type 1 diabetes, which was due to concerns about safety and the potentially increased risk for diabetic ketoacidosis in this population, noted Wheeler.