
Dapagliflozin is known to improve kidney outcomes in patients with chronic kidney disease (CKD), but it is unclear what effect late initiation of the drug has when eGFR is <25 mL/min/1.73m2.
To improve understanding, Chi-Chih Hung, Yi-Wen Chiu, and Shang-Jyh Hwang studied the efficacy and safety of dapagliflozin in patients with CKD stages 4 and 5. They shared findings during the oral presentation, Efficacy and Safety of Dapagliflozin in Patients with CKD Stages 4-5 at ASN Kidney Week 2024.
The DAPA advKD trial (NCT05196347) was a randomized5p-, open-label trial that recruited 180 patients with eGFR 10-30 mL/min/1.73m2 and eGFR decline ≥2.5 mL/min/1.73m2/year. These patients were randomized 2:1 to dapagliflozin (5-10 mg/d) plus integrated CKD care, or integrated CKD care only.
The primary study outcome was maintenance of eGFR decline ≥0.75 ml/min/1.73m2/year. The first secondary outcome was renal endpoint (a composite of renal replacement therapy, eGFR <5 mL/min/1.73m2, renal or cardiovascular [CV] death, or a >50% eGFR decline). The second secondary outcome was renal and CV endpoint (a composite of renal outcome as defined above, acute kidney injury [AKI], and heart failure). Predefined safety outcomes were measured.
During a median period of 1.62 years, total eGFR slopes were -2.24 mL/min/1.73m2/year (-4.70 to -0.62 mL/min/1.73m2/year) for the dapagliflozin group and -3.67 mL/min/1.73m2/year (-7.16 to -1.25 mL/min/1.73m2/year) for the control group. The primary outcome of eGFR slope decline was 1.06 ml/min/1.73m2/year (0.10 to 0.32 ml/min/1.73m2/year; P=.019, linear mixed model).
The secondary renal outcome occurred in 24/120 (20%) patients in the dapagliflozin group, and in 21/60 (35%) in the control group (HR, 0.50 [0.28 to 0.89], P=.019). The secondary renal and CV outcome occurred in 25/120 (21%) patients in the dapagliflozin group and 21/60 (35.0%) in the control group (HR, 0.52 [0.29 to 0.93], P=.028). The control group experienced higher rates of heart failure and AKI but had a higher incidence of eGFR decline.
The researchers concluded, “Among patients with eGFR 10-30 mL/min/1.73m2, the risks of eGFR decline and composite renal outcomes were lower with dapagliflozin than with control group.”
Source: Hung C-C, Chiu Y-W, Hwang S-J. Efficacy and safety of dapagliflozin in patients with CKD stages 4-5. SA-OR96. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 26, 2024; San Diego, California. Funding was provided by AstraZeneca.