Dapagliflozin Reduces Risk for Kidney Events in IgA Nephropathy

kidney cross section
kidney cross section
In patients with IgA nephropathy, dapagliflozin significantly reduced the risk of CKD progression when added to ACEi/ARB therapy.

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/1.73m2 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 −4.7mL/min/1.73m2 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. [published online April 17, 2021]. Kidney Int. doi: 10.1016/j.kint.2021.03.033

This article originally appeared on Renal and Urology News