POS-832 DAPAGLIFLOZIN IN IgA NEPHROPATHY: FINDINGS FROM THE DAPA-CKD TRIAL
Recommended Citation
Lambers Heerspink H, Toto RD, Jongs N, Vart P, Chertow GM, Hou FF, McMurray JJV, Pecoits-Filho R, Correa-Rotter R, Rossing P, Sjöström CD, Stefánsson BV, Umanath K, Langkilde AM, and Wheeler DC. POS-832 DAPAGLIFLOZIN IN IgA NEPHROPATHY: FINDINGS FROM THE DAPA-CKD TRIAL. Kidney Int Rep 2021; 6(4):S362.
Document Type
Conference Proceeding
Publication Date
4-1-2021
Publication Title
Kidney Int Rep
Abstract
Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Despite the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, up to 40% of patients with IgAN are at risk of progressing to end-stage kidney disease (ESKD). Additional therapies to slow kidney function decline are highly desired. The DAPA-CKD trial demonstrated that the sodium glucose co-transporter 2 inhibitor dapagliflozin significantly reduced the risk of kidney failure and prolonged survival in participants with chronic kidney disease with and without type 2 diabetes. The DAPA-CKD population included patients with IgAN. We determined the long-term efficacy and safety of dapagliflozin on major kidney and cardiovascular outcomes in these patients. Methods: Patients with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g, were randomized to dapagliflozin (10 mg once daily) or placebo. The primary endpoint was a composite of sustained decline in eGFR ≥50%, ESKD, or kidney or cardiovascular death and was analyzed by Cox proportional hazard regression. This subanalysis was conducted in patients with an IgAN diagnosis. Results: Of the 270 participants with IgAN (93% confirmed by a previous kidney biopsy), 137 were assigned to dapagliflozin and 133 to placebo. Their mean (SD) age was 51.2 (13.1) years, eGFR was 43.8 (12.2) ml/min/1.73m2 and median UACR was 900 (25th to 75th Percentile 540-1515) mg/g. Median follow-up was 2.4 years. The primary outcome occurred in 6 patients (4.4%) in the dapagliflozin group and 20 patients (15%) in the placebo group (hazard ratio, 0.29; 95% confidence interval, 0.12-0.73). An abstract including secondary outcomes, eGFR trajectories and effects on UACR and blood pressure will be submitted by 10 February 2021, and we plan to present these results at the World Congress of Nephrology, 2021. Conclusions: Of the 270 participants with IgAN (93% confirmed by a previous kidney biopsy), 137 were assigned to dapagliflozin and 133 to placebo. Their mean (SD) age was 51.2 (13.1) years, eGFR was 43.8 (12.2) ml/min/1.73m2 and median UACR was 900 (25th to 75th Percentile 540-1515) mg/g. Median follow-up was 2.4 years. The primary outcome occurred in 6 patients (4%) in the dapagliflozin group and 20 patients (15%) in the placebo group (hazard ratio, 0.29; 95% confidence interval [CI], 0.12-0.73). Mean annual rates of eGFR decline with dapagliflozin and placebo were −3.5 and −4.7 mL/min/1.73m2/year (difference 1.2 [95%CI, −0.12-2.51] mL/min/1.73m2). Dapagliflozin reduced UACR by 26% (95%CI, 14-37) relative to placebo. Adverse events leading to study drug discontinuation were similar with dapagliflozin and placebo; there were fewer serious adverse events with dapagliflozin.
Volume
6
Issue
4
First Page
S362
Comments
Conflict of Interest: This study was funded by AstraZeneca. Dr. Heerspink reports grants and honoraria (paid to his employer) from AstraZeneca, Janssen, Abbvie and Boehringer Ingelheim, and honoraria (paid to his employer) from Merck, Gilead, Mitsubishi Tanabe, Mundipharma, Retrophin, Bayer, Chinook, Novo Nordisk and CSL Pharma.
https://doi.org/10.1016/j.ekir.2021.03.870