Effects of Dapagliflozin on Progression of CKD According to Different Rates of Pretrial eGFR Loss

Key Points eGFR slope before a clinical trial may assist in selecting participants at risk of kidney outcomes in whom new therapies are needed. In a post hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial, we showed that the pretrial eGFR trajectory was associated with CKD progression. Patients who demonstrated rapid progression in advance of the trial experienced more pronounced benefits of dapagliflozin. Background Identification of patients likely to experience substantial loss of 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 before enrollment (pretrial eGFR slope) in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease study. Methods We recorded eGFR data for 2 or less to 2 years from electronic medical records for 4304 patients with CKD before enrollment in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease study. 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 end point. 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 three or more historical eGFR measurements were evaluated (mean [SD] pre-enrollment eGFR slope: −6.1 [6.1] ml/min per 1.73 m 2 /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 preinclusion eGFR trajectory (rapid progressors; eGFR slope <−5 ml/min per 1.73 m 2 /year), as was the benefit of dapagliflozin on the kidney composite end point ( P interaction 0.02). Conclusions Determination of pretrial 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. Clinical Trial Registry Name and Registration Number: NCT03036150