Abstract: TH-PO1049
Benefits of Dapagliflozin in Slowing eGFR Decline in Patients with Different Rates of eGFR Loss
Session Information
- CKD: Therapeutic Advances
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Jongs, Niels, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Sjostrom, David, Late-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Chertow, Glenn M., Departments of Medicine and Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California, United States
- Toto, Robert D., Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States
- Wheeler, David C., Department of Renal Medicine, University College London, London, United Kingdom
- Heerspink, Hiddo Jan L., Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Background
Inclusion of patients likely to experience a loss of estimated glomerular filtration rate (eGFR) is required to detect a kidney protective treatment effect in clinical trials. This is usually achieved by enrolling patients with high levels of albuminuria. However, not all patients with elevated albuminuria show a progressive loss of kidney function. eGFR slope before the trial may better predict whether patients experience a loss in eGFR during a clinical trial. We assessed the effect of dapagliflozin on eGFR slope according to patient eGFR slope prior to inclusion in the DAPA-CKD trial (pre-inclusion eGFR slope).
Methods
We recorded eGFR data for ≤2 years from electronic medical records for 4304 patients with CKD before enrollment in DAPA-CKD, a randomized, placebo-controlled trial of dapagliflozin. We used linear regression to estimate within-patient pre-inclusion eGFR slopes. We evaluated the association of pre-inclusion eGFR slope with total (randomization to end-of-treatment) and chronic (Week 2 to end-of-treatment) eGFR slopes using a two-slope linear mixed-effects model. The composite kidney endpoint was defined as sustained ≥50% eGFR decline, end-stage kidney disease, or death from kidney causes.
Results
In total, 870 (20.2%) patients with ≥3 historical eGFR measurements were evaluated (mean pre-inclusion eGFR slope [SD]: −6.15 [6.1]). The benefit of dapagliflozin in reducing the total (p-interaction: 0.018) and chronic (p-interaction: 0.022) eGFR slopes was more pronounced in patients with steeper pre-inclusion eGFR slopes (rapid progressors; Figure). The effect of dapagliflozin compared to placebo on the composite kidney endpoint was also more pronounced in rapid progressors (p-interaction: 0.023).
Conclusion
Determination of pre-trial eGFR slope may help to identify patients with CKD at higher and lower risks of progression and those more or less likely to benefit from a targeted intervention to slow kidney function loss.
Funding
- Commercial Support – AstraZeneca