Abstract: TH-PO1057
Associations Between Albuminuria and Clinical Outcomes in Patients with CKD with and Without Diabetes: New Insights from DAPA-CKD
Session Information
- CKD Progression and Complications: Diagnosis, Prognosis, Risk Factors
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- van Mil, Dominique, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands
- Vart, Priya, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands
- Schechter, Meir, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands
- Jongs, Niels, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands
- Chertow, Glenn, Stanford University School of Medicine, Stanford, California, United States
- Correa-Rotter, Ricardo, The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico
- Langkilde, Anna Maria, BioPharmaceuticals R&D AstraZeneca, Gothenburg, Sweden
- Rossing, Peter, Steno Diabetes Center Copenhagen, Copenhagen, Denmark
- 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, Groningen, Netherlands
Background
Albuminuria is a strong determinant of kidney and cardiovascular (CV) risk in patients with chronic kidney disease (CKD) with and without type 2 diabetes (T2D). Early albuminuria reduction may be an indicator of decreased risk. In the DAPA-CKD trial, dapagliflozin reduced the risk of kidney and CV events in patients with CKD with similar effects in those with and without T2D. We examined risk associations between baseline and early changes in albuminuria and kidney outcomes in patients with CKD with and without T2D.
Methods
In DAPA-CKD, 4304 patients with and without T2D with urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and eGFR of 25–75 mL/min/1.73m2 were randomized to receive dapagliflozin 10 mg or placebo daily, on top of standard of care, and followed for a median 2.4 years. We assessed associations among baseline UACR, early change in UACR (baseline to Month 4), and the primary outcome (≥50% eGFR decline, end-stage kidney disease, death from a kidney or CV cause) using multivariable adjusted Cox regression analyses.
Results
Every doubling of baseline UACR was associated with a near doubling of risk: hazard ratio (HR) 1.89 (95% confidence interval [CI] 1.71–2.08) in patients with T2D and 1.84 (95% CI 1.54–2.20) in those without T2D. Dapagliflozin reduced UACR (placebo-adjusted) from baseline to Month 4 by 35.7% (95% CI 29.0–42.5) in participants with T2D and 19.7% (95% CI 10.6–28.8) in those without T2D, with a large between-individual variation in both treatment groups. The HR for every 50% decline in UACR from baseline to Month 4 was 0.86 (95% CI 0.79–0.93) and 0.70 (95% CI: 0.59–0.83) in participants with and without T2D, respectively.
Conclusion
In patients with CKD with and without T2D, higher baseline albuminuria was associated with a higher risk of progressive kidney disease or cardiovascular death, and early albuminuria reduction was associated with a decreased risk. Because dapagliflozin reduced clinical outcomes in patients with and without T2D but reduced albuminuria to a larger degree in those with T2D, these findings suggest that the clinical benefits gained via dapagliflozin’s albuminuria-reducing effects are more potent among patients with T2D.
Funding
- Commercial Support – AstraZeneca