Kidney Week

Abstract: SA-OR006

Characterization of the Acute eGFR Response to SGLT2-Inhibition with Empagliflozin

Session Information

• AKI: Onco-Nephrology and Other Drugs
  November 09, 2019 | Location: Salon A/B, Walter E. Washington Convention Center
  Abstract Time: 05:30 PM - 05:42 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Wanner, Christoph, University Hospital, Wuerzburg, Germany

Christoph Wanner, MD



Christoph Wanner is Professor of Medicine and head of the Division of Nephrology at the University Hospital of Würzburg, Germany He has published more than 700 scientific articles (HF 79) on diabetic kidney disease, lipid disorders, statin treatment and rare kidney diseases. He is steering committee member of the EMPA-REG Outcome, EMPEROR and EMPA-KIDNEY trials, aiming in slowing the progression of kidney disease and improving cardiovascular outcomes. He is an Associate Editor of the Clinical Journal of the America Society of Nephrology. He has received the 2016 Award from the ERA-EDTA for Outstanding Clinical Contributions to Nephrology and in 2018 from the DGfN the Franz Volhard medaille. He is President Elect of the ERA-EDTA

• Kraus, Bettina J., University Hospital, Wuerzburg, Germany

Bettina J. Kraus,

• Weir, Matthew R., University of Maryland School of Medicine, Baltimore, Maryland, United States

Matthew R. Weir,

• Bakris, George L., The University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris,

• Cherney, David, University of Toronto, Toronto, Ontario, Canada

David Cherney,

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

Hiddo Jan L Heerspink,

• Inzucchi, Silvio E., Yale University School of Medicine, New Haven, Connecticut, United States

Silvio E. Inzucchi,

• Zinman, Bernard, Mount Sinai Hospital, Toronto, Ontario, Canada

Bernard Zinman,

• Ritter, Ivana, Boehringer Ingelheim International GmbH, Ingelheim, Germany

Ivana Ritter,

• Mattheus, Michaela, Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany

Michaela Mattheus,

• von Eynatten, Maximilian, Boehringer Ingelheim International GmbH, Ingelheim, Germany

Maximilian von Eynatten,

• Koitka-Weber, Audrey, Boehringer Ingelheim International GmbH, Ingelheim, Germany

Audrey Koitka-Weber,

Background

Empagliflozin (EMPA) reduces cardiovascular (CV) and renal risk in type 2 diabetes patients with established CV disease. As shown with RAAS blockade, EMPA also causes an acute eGFR decrease after treatment initiation. Although considered hemodynamic and reversible, it needs to be better understood to avoid premature drug discontinuation.

Methods

In EMPA-REG OUTCOME^®, 6,668 participants who received at least one dose of study drug and had an eGFR value at both baseline and week 4 were categorized by % acute eGFR change to: >10% decrease, >0% to ≤10% decrease, ≤0% decrease. eGFR over time was analyzed using mixed model repeated measures. Acute renal failure (ARF) incidence was based on investigator-reported adverse events according to the narrow standardized MedDRA query.

Results

As expected, there were more patients with a >10% decrease in EMPA (28.3%) than in PBO (13.4%); however, an acute eGFR drop >30% with EMPA was rare (1.4%). After initial dynamics, long-term eGFR remained stable in all categories on EMPA (Figure). In multivariate regression analyses, KDIGO risk category (elevated UACR/low eGFR) and diuretic use at baseline were independent predictors of an acute eGFR decrease >10% with EMPA. From baseline to week 4, irrespective of the magnitude of the eGFR decrease, overall adverse events (AEs) and serious AEs were similar or lower with EMPA than PBO. ARF was more frequent in patients experiencing an acute eGFR decrease >10% in both groups, however most were reported as ‘renal impairment’. During chronic treatment, overall and renal safety profiles were similar between PBO and all categories on EMPA.

Conclusion

Given the known renal protection with SGLT2 inhibition, our data demonstrate a relatively modest acute eGFR decrease with treatment, less likely to cause discontinuation of this reno-protective therapy.

Funding

• Commercial Support – Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance