Dapagliflozin effectively reduces the risk for kidney disease progression in patients with immunoglobulin A nephropathy (IgAN) regardless of diabetes status, according to results from a pre-specified analysis of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) trial.
The original trial included 270 participants with IgAN who had an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g and were receiving a stable dose of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). No one could be currently receiving immunotherapy. Investigators randomly assigned 137 patients to dapagliflozin (10 mg/d), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and 133 to placebo.
Compared with placebo, dapagliflozin treatment was associated with a significant 71% lower risk of the primary composite endpoint, which included a sustained decline in eGFR of 50% or more, end-stage kidney disease (ESKD), or death from a kidney disease-related or cardiovascular cause over a median 2.1 years. The absolute risk reduction with dapagliflozin was 10.7% overall, David C. Wheeler, MD, of the University College London in the UK, and colleagues reported in Kidney International. Among high-risk patients – those with baseline eGFR less than 45 mL/min/1.73 m2 or UACR exceeding 1000 mg/g – dapagliflozin was associated with an absolute risk reduction in the primary composite endpoint of −9.2% and −18.3%, respectively, they reported. Results were consistent when analyses were limited to patients with biopsy-proven IgAN.
Mean eGFR declined less with dapagliflozin than placebo: −3.5 vs −4.7 mL/min/1.73 m2 per year, respectively. UACR decreased by 26% with dapagliflozin vs placebo.
Dapagliflozin also significantly decreased the risk of a composite renal endpoint (a sustained decline in eGFR of 50% or more, ESKD, or death from a kidney disease-related cause) by 76% and ESKD by 70%, Dr Wheeler’s team reported.
Serious adverse events occurred in a smaller proportion of the dapagliflozin than placebo group: 16.1% vs 25.6%. No patients experienced ketoacidosis or severe hypoglycemia with dapagliflozin.
“Given the paucity of event-driven trials in IgA nephropathy, clinicians and patients are likely to welcome a novel therapeutic approach that can be used as an adjunct to ACEi/ARB treatment (or where ACEi/ARB treatment is contraindicated),” Dr Wheeler’s team concluded.
Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.
Wheeler DC, Toto RD, Stefansson BV, et al; for the DAPA-CKD Trial Committees and Investigators. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. Published online April 17, 2021. doi:10.1016/j.kint.2021.03.033