Abstract

Background Dapagliflozin reduces kidney failure risk in patients with chronic kidney disease (CKD) but can result in a reversible acute reduction in estimated glomerular filtration rate (eGFR) upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown. Methods The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to oncedaily dapagliflozin 10 mg or placebo. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (>10% or >0 to 10%) or an increase in eGFR from baseline to 2 weeks, and assessed long-term efficacy and safety. Results A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFR >10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFR >10% experienced a long-term eGFR decline of -1.58 mL/min per 1.73m2 per year compared with -2.44 and -2.48 mL/min per 1.73m2 per year among those experiencing a less pronounced reduction or increase in eGFR, respectively (P-interaction, 0.05). In the placebo group, long-term eGFR decline was -3.27, -3.84, and -3.77 mL/min per 1.73m2 per year for acute eGFR reduction subgroups of >10%, >0 to 10%, or increase in eGFR (P-interaction, 0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change. Conclusions Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression.

View details for DOI 10.1681/ASN.2022030306

View details for PubMedID 35977807