Background

Dapagliflozin lowers the risk of kidney failure in patients with chronic kidney disease with and without type 2 diabetes in the DAPA-CKD trial. The present study was conducted to evaluate the effect of dapagliflozin on the rate of alteration in estimated glomerular filtration rate (eGFR)-i.e., the eGFR slope.

Methodology

DAPA-CKD was a randomized controlled trial that recruited participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio (UACR) of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1.73m². 

In this prespecified analysis, the authors analyzed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope). 

Results

4304 participants were enrolled between Feb 2, 2017, and April 3, 2020. About 2152 (50%) were assigned to dapagliflozin, and 2152 (50%) were assigned to a placebo. From baseline to the end of treatment, dapagliflozin, compared with placebo, slowed eGFR decline by 0.95mL/min per 1.73 m² per year (95% CI 0.63 to 1.27) in the overall cohort. Between baseline and week 2, dapagliflozin compared with placebo led to acute eGFR reduction of 2.61 mL/min per 1.73 m² (2.16 to 3.06) in patients with type 2 diabetes and 2.01 mL/min per 1.73 m² (1.36 to 2.66) in those without type 2 diabetes. The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was more effective in patients with higher baseline HbA1c and UACR. 

Conclusion

Dapagliflozin significantly reduced long-term eGFR reduction in patients with chronic kidney disease compared with placebo. Also, the mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and raised UACR. 

Reference

Heerspink HJL, et al. Lancet Diabetes Endocrinol. 2021; 9 (11): 743754.