Wheeler DC, Toto RD, Stefansson BV, Jongs N, Chertow GM, Greene T, Hou FF, McMurray JJV, Pecoits-Filho R, Correa-Rotter R, Rossing P, Sjöström CD, Umanath K, Langkilde AM, and Heerspink HJL. A pre-specified analysis of the DAPA-CKD trial indicates effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int 2021.
Immunoglobulin A (IgA) nephropathy is a common form of glomerulonephritis, which despite use of renin-angiotensin-aldosterone-system blockers and immunosuppressants, often progresses to kidney failure. In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, dapagliflozin reduced risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes, including those with IgA nephropathy. Here we randomized participants with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m(2) and urinary albumin-to-creatinine ratio 200-5000 mg/g (22.6-565 mg/mol) to dapagliflozin 10mg or placebo, as adjunct to standard care The primary composite endpoint was a sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from a kidney disease-related or cardiovascular cause. Of 270 participants with IgA nephropathy (254 [94%] confirmed by previous biopsy), 137 were randomized to dapagliflozin and 133 to placebo, and followed for median 2.1 years. Overall, mean age was 51.2 years; mean eGFR, 43.8 mL/min/1.73m(2); and median urinary albumin-to-creatinine ratio, 900 mg/g. The primary outcome occurred in six (4%) participants on dapagliflozin and 20 (15%) on placebo (hazard ratio, 0.29; 95% confidence interval, 0.12, 0.73). Mean rates of eGFR decline with dapagliflozin and placebo were -3.5 and -4.7 mL/min/1.73m(2)/year, respectively. Dapagliflozin reduced the urinary albumin-to-creatinine ratio by 26% relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo. There were fewer serious adverse events with dapagliflozin. It had no new safety findings in this population. Thus, in participants with IgA nephropathy, dapagliflozin reduced the risk of chronic kidney disease progression with a favorable safety profile.
ePub ahead of print