Kidney Week

Abstract: PO2368

Correlates and Consequences of an Acute Decline in Estimated Glomerular Filtration Rate in Response to the SGLT-2 Inhibitor Dapagliflozin

Session Information

• CKD: Insights from Recent Clinical Trials and Large Real-World Effectiveness Studies
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• L Heerspink, Hiddo Jan, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink, PhD

• Jongs, Niels, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Niels Jongs,

• Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States

Glenn Matthew Chertow,

• Langkilde, Anna Maria, AstraZeneca, Gothenburg, Sweden

Anna Maria Langkilde,

• McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom

John McMurray,

• Correa-Rotter, Ricardo, The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico

Ricardo Correa-Rotter,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

• Sjostrom, David, AstraZeneca, Gothenburg, Sweden

David Sjostrom,

• Stefansson, Bergur V., AstraZeneca, Gothenburg, Sweden

Bergur V. Stefansson,

• Toto, Robert D., UT Southwestern Medical Center, Dallas, Texas, United States

Robert D. Toto,

• Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States

Tom Greene,

• Wheeler, David C., University College London, London, London, United Kingdom

David C. Wheeler,

Background

In the DAPA-CKD trial (NCT03036150), dapagliflozin slowed the rate of progression of chronic kidney disease (CKD) in CKD patients with and without type 2 diabetes. However, dapagliflozin can cause a reversible acute decline in estimated glomerular filtration rate (eGFR), which is considered to be a hemodynamic effect. Predictors of the initial eGFR decline and its association with safety outcomes are unknown.

Methods

In DAPA-CKD, 4304 participants with urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g and eGFR 25–75 mL/min/1.73m² were randomized to dapagliflozin 10 mg or placebo once daily, added to standard care, and followed for median 2.4 years. We categorized decline in eGFR from baseline to Week 2 in percentages (>10% decline; between 0 and 10% decline; and no decline) and absolute changes (>3 mL/min/1.73m²; between 0 and 3 mL/min/1.73m²; and no decline).

Results

A total of 4157 patients (96.6% of full cohort) had eGFR data available at baseline and Week 2. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%) experienced an acute decline in eGFR of >10%, respectively. The odds ratio for a decline in eGFR of >10% with dapagliflozin compared with placebo was 3.2 (95%CI 2.8–3.6; p<0.001). The odds ratio for an acute eGFR decline of >10% was consistent across patient subgroups defined by baseline sex, eGFR, UACR, diabetes status, blood pressure, body mass index, or cardiovascular disease history. The only exception was that white participants and participants ≥65 years were more likely to experience an acute eGFR decline of >10% following dapagliflozin initiation relative to placebo (interaction p<0.025 for both). Rates of serious adverse events and adverse events of special interest in those treated with dapagliflozin were unrelated to the degree of acute eGFR decline.

Conclusion

Although acute declines in eGFR occurred more frequently with dapagliflozin, it is not associated with an increased risk of adverse events, supporting the safe use of dapagliflozin in patients with CKD stage 2 to 4.

Funding

• Commercial Support – AstraZeneca