Abstract: TH-PO1050
Implications of Acute GFR Change for the Effect of SGLT2 Inhibitors on Long-Term End Points
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
- Berchie, Ransmond O., University of Utah Health, Salt Lake City, Utah, United States
- Inker, Lesley Ann, Tufts University, Medford, Massachusetts, United States
- Heerspink, Hiddo Jan L., Universiteit Groningen Afdeling Gezondheidswetenschappen, Groningen, Groningen, Netherlands
- Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States
Background
Several studies have reported that chronic kidney disease (CKD) patients often experience a substantial decline in glomerular filtration rate (GFR) within 1 month after initiating treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i). Our goal is to determine, to the extent possible from the data, how the expected effect of SGLT2i on the time to kidney failure is modified by knowledge of the acute GFR change (△GFR) after starting SGLT2i.
Methods
We used a Johnson SU model for the distribution of △GFR within the SGLT2i and control groups and a Fine-Grey model with cubic splines to relate △GFR to the time to kidney failure with death as a competing risk for 3 clinical trials: DAPA-CKD, EMPA-REG, and CREDENCE. Then, using the modern causal inference framework of principal stratification, we specified the unobservable correlation ρ between △GFR under the SGLT2i and control treatments as a sensitivity parameter. This allowed us to define the distribution of △GFR under the control consistent with an observed △GFR with the SGLT2i and thereby estimate the effects of SGLT2i on the time to kidney failure conditional on △GFR across different possible values for ρ.
Results
Across all values of ρ, we find no evidence that negative acute GFR changes after SGLT2i initiation indicate an adverse effect or reduction in the benefit of SGLT2i on kidney failure. Moreover, for ρ≥0.7, we observe a trend suggesting that more negative acute changes signify a greater benefit of SGLT2i on the time to kidney failure.
Conclusion
The findings suggest that larger than average GFR reductions 1 month after initiating SGLT2i do not signify reduced benefit on kidney failure and may indicate therapeutic effectiveness.
The Figure shows the impact of △GFR on the estimated effect of SGLT2i treatment on the probability of kidney failure by 2 years.
Funding
- Private Foundation Support