Efficacy and Safety of Dapagliflozin in the Treatment of Adult Primary IgA Nephropathy: A Single-Center, Prospective, Open, Randomized Controlled Study

Background: Despite optimized renin-angiotensin-aldosterone system ( RAAS ) inhibition, 20 % ~ 40 % of immunoglobulin A nephropathy (IgAN) patients will progress to end-stage renal disease within 10 ~ 20 years after diagnosis. We evaluated the efficacy and safety of dapagliflozin, when added to the treatment regimen of patients with IgAN. Methods: Participants had IgAN proven by kidney biopsy(proteinuria with protein excretion of 0.3-3.5 g/d , serum albumin ＞ 30g/L and estimated glomerular filtration rate（eGFR)） > 30 mL/min/1.73 m2 ) and were receiving optimized RAAS inhibitor therapy. Patients were randomly assigned 1:1 to receive daily oral dapagliflozin or not for 6 months.The primary outcome was percentage change in 24-hour urine protein excretion(24HUPE), first-morning urine albumin-creatinine ratio (UACR) between baseline and 6 months. Results: 60 participants (mean eGFR, 83.17 mL/min/1.73 m2; median 24HUPE 0.77 g/d; median UACR 636mg/g.Cr) were recruited and randomly assigned to receive dapagliflozin(n = 30) or not (n = 30). Percentage change in 24HUPE at 6 months was significantly different between the dapagliflozin group and the control group (45.8% [inter quartile range (IQR), 65.2%, 4.2%] vs 10.1% [IQR, −46.1%, 53.1%]; P < 0.05, respectively). At 6 months, median 24HUPE level was significantly lower in the dapagliflozin group than control group (0.35 [IQR, 0.18, 0.75] g/d vs 0.62 [IQR, 0.37, 1.21] g/d; P < 0.05, respectively). The change trend of UACR was the same as that of 24HUPE. No serious adverse events were recorded during the study in either study group. Conclusion: Dapagliflozin in addition to optimized RAAS inhibition significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse events.These findings require confirmation in larger treatment trials. Funding: Government Support – Non-U.S.