Effects of Dapagliflozin on Progression of Chronic Kidney Disease According to Different Rates of Pre-Trial Progression

Background: Identification of patients likely to experience substantial loss of estimated glomerular filtration rate (eGFR) is required to detect a kidney protective treatment effect in clinical trials; this is usually achieved by restricting inclusion of patients with elevated albuminuria. However, not all patients with elevated albuminuria show progressive eGFR loss. The eGFR slope before the trial may better predict whether patients experience loss in eGFR during the trial. We assessed the effect of dapagliflozin on eGFR slope according to patients’ eGFR slope prior to enrollment (pre-trial eGFR slope) in the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) . Methods: We recorded eGFR data for less than or equal to two years from electronic medical records for 4304 patients with CKD before enrollment in DAPA-CKD. We used linear regression to estimate within-patient pre-enrollment eGFR trajectory. We evaluated the association of pre-enrollment eGFR trajectory with total and chronic eGFR slopes and a kidney composite endpoint. We also determined the degree to which pre-enrollment eGFR trajectory modified the effects of dapagliflozin. Results: Eight hundred and seventy (20% of the total cohort) patients with more than or equal to three historical eGFR measurements were evaluated (mean [standard devitation (SD)] pre-enrollment eGFR slope: −6.1 [6.1] mL/min/1.73m²/year). The benefit of dapagliflozin in reducing total (p-interaction 0.02) and chronic (p-interaction 0.02) eGFR slopes was more pronounced in patients with steeper pre-inclusion eGFR trajectory (rapid progressors; eGFR slope <−5 mL/min/1.73m²/year), as was the benefit of dapagliflozin on the kidney composite endpoint (p-interaction 0.02). Conclusions: Determination of pre-trial eGFR trajectory may help to identify patients with CKD at higher and lower risks of progression and those more likely to benefit from targeted intervention.