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Dapagliflozin (Farxiga) was renoprotective and cardioprotective in patients with most causes of kidney disease with or without type 2 diabetes, a secondary analysis of the DAPA-CKD trial found.

In another look at the over 4,300 patients from the original trial, once-daily treatment with 10 mg of dapagliflozin significantly reduced the risk for the composite of a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from cardiovascular or kidney causes -- the primary endpoint -- regardless of the underlying cause of kidney disease (hazard ratio [HR] 0.61, 95% CI 0.51-0.72), said David Wheeler, MD, of the George Institute for Global Health in Sydney, Australia, during a presentation at the American Society of Nephrology's virtual Kidney Week.

And when broken down by etiology of kidney disease, dapagliflozin significantly reduced the risk for this composite 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) compared with placebo.

However, patients whose kidney disease was caused by ischemic/hypertensive chronic kidney disease (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 versus placebo over a 32-month follow-up period (HR 0.29, 95% CI 0.12-0.73).

"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," Wheeler pointed out.

"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," he noted.

Similar findings were reported when only looking at renal-specific outcomes, defined as a sustained 50% or more eGFR decline, progression to end-stage kidney disease, or renal death. Overall, there was a 44% reduced risk for this outcome with dapagliflozin versus placebo (HR 0.56, 95% CI 0.45-0.68).

For those whose kidney disease was caused by diabetic nephropathy, there was a 45% reduced risk for this composite renal outcome (HR 0.55, 95% CI 0.43-0.71), while those whose kidney disease was caused by glomerulonephritides saw a 57% reduced risk for this renal outcome with dapagliflozin (HR 0.43, 95% CI 0.26-0.72).

Again, patients whose kidney disease was specifically caused by ischemic or hypertensive CKD (HR 0.74, 95% CI 0.40-1.36) or other/unknown causes (HR 0.81, 95% CI 0.35-1.83) didn't see a significant reduced risk for this renal outcome with dapagliflozin versus placebo.

When looking only at cardiovascular outcomes, only those whose kidney disease was caused by diabetic nephropathy saw a significantly reduced risk for cardiovascular death or hospitalization for heart failure with dapagliflozin (HR 0.67, 95% CI 0.50-0.90). Patients with all other underlying kidney disease etiologies didn't see a significant cardiovascular benefit.

In the same vein, only those with diabetic nephropathy saw a significantly reduced risk for all-cause mortality (HR 0.72, 95% CI 0.54-0.97).

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

All 4,304 participants in the DAPA-CKD trial had chronic kidney disease with an eGFR of 25 to 75 mL/min/1.73m² and a urine albumin-to-creatinine ratio of 200 to 5,000 mg/g.

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