Abstract: FR-PO0161
Store-Operated Calcium-Channel Inhibitor Auxora Improves Kidney Function Following Ischemia-Induced AKI in Rats
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Lewis, Alexander, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Ullah, Md Mahbub, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Hebbar, Sudarshan, CalciMedica Inc, San Diego, California, United States
- Stauderman, Kenneth A, CalciMedica Inc, San Diego, California, United States
Background
Activation of immune and vasoactive pathways contribute to the development of acute kidney injury (AKI). Both endothelial cells and CD4+ lymphocytes express the store-operated calcium channel Orai1 and previous studies suggest that Orai1 activity contributes to activation of T-helper 17 cells in AKI of rats and humans. This study sought to evaluate the selective Orai1 store-operated calcium channel inhibitor Auxora (CM4620) on the development or recovery from AKI in a rat model of ischemia reperfusion injury.
Methods
In study I, male Sprague-Dawley rats (~250-300 g), instrumented with chronic indwelling jugular catheters were subjected to bilateral renal ischemia (40 minutes) and reperfusion (I/R) or sham-surgery. Treatment of rats with Auxora (16 mg/kg over 4 hours i.v.) or placebo was initiated within 30 min I/R and GFR was evaluated 24 h post I/R by transcutaneous clearance of FITC-sinistrin. Study II evaluated effects of Auxora on renal function following established loss of GFR, determined by FITC-sinistrin clearance between 2-4 h post I/R. Rats were then randomized and Auxora or placebo treatment initiated at 6 hours post I/R and repeated at 24 and 48 hours. GFR was then evaluated at 72 h post I/R.
Results
In study I, GFR was 0.81±0.11 ml/min/100g b.w in sham-controls and markedly reduced by 73% in placebo-treated post I/R rats 24 h post I/R (0.22 ± 0.04 ml/min/100g). The reduction in GFR was significantly attenuated in Auxora-treated rats (0.35 ± 0.04 ml/min/100g b.w.; p<0.05 vs. placebo). The number of Th17 cells (CD4+/IL17+) in kidney was attenuated by approximately 50% in Auxora-treated rats vs. placebo (p<0.05). In study II, there was ~50% reduction of GFR between 2-4 h post-I/R rats vs. baseline; there was no difference in GFR was present at time of randomization (0.43±0.02 vs 0.39±0.05 ml/min/100g in placebo vs. Auxora, respectively). GFR recovery was significantly greater in Auxora-treated animals vs. placebo controls (0.81±0.03 vs. 0.47±0.04 ml/min/100g, respectively; p<0.001) 72 h following I/R.
Conclusion
These data suggest Auxora has therapeutically beneficial effects in a rat model of AKI and can hasten recovery of renal function. The basis for improved function may relate to alterations in inflammation and/or improved vascular function.
Funding
- NIDDK Support – CalciMedica Inc