Abstract: FR-PO155
AMPK Activation Protects Kidney Function After Renal Ischemia Reperfusion Injury in Rats
Session Information
- AKI: Mechanisms - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Frikke-Schmidt, Henriette, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Albarazanji, Kamal Ahmed, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Qi, Jenson, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Frederick, David, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Du, Fuyong, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Meng, Rong, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Ho, George, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Nawrocki, Andrea R., Janssen Research and Development LLC, Spring House, Pennsylvania, United States
- Pocai, Alessandro, Janssen Research and Development LLC, Spring House, Pennsylvania, United States
Group or Team Name
- Cardiovascular, Metabolism, Retina and Pulmonary Hypertension Therapeutic Area.
Background
The kidney has a high energy demand to carry out its function, and with Acute Kidney Injury (AKI) such as ischemia reperfusion, there is profound mitochondrial damage. Adenosine Monophosphate Kinase (AMPK) is a key regulator of mitochondrial function and biogenesis. Here, we used a rat model of ischemia-reperfusion inducing AKI to explore the effect of pharmacological activation of AMPK.
Methods
Male Spraque Dawley rats were treated with a direct AMPK activator (n=12) or vehicle (n=12) one hour prior to ischemia reperfusion induced by bilateral clamping the renal pedicles for 35 minutes. Kidney functions was assessed by transcutaneous glomerular filtration rate (tGFR) measured at 5-7 hours using the Medibeacon technology, and kidney, plasma and urine were collected for analysis of plasma creatinine, urinary NephroCheck and kidney histology 7 hours post injury.
Results
Plasma creatinine and tGFR were significantly improved in the animals treated with AMPK activator compound compared to vehicle control with a 28% reduction of creatinine (1.53±0.257 versus 1.10±0.184 mg/dl, p<0.001) and 69% improvement in tGFR (0.0792± 0.0452 versus 0.135±0.0738 ml/min/100g bodyweight, p<0.05). AMPK activation improved urinary NephroCheck score (0.0764±0.0564 versus 0.00899±0.00356 (ng/ml)2/1000 of IGFBP7 and TIMP2, p<0.001) and acute tubular necrosis in the cortex.
Conclusion
Pharmacological activation of AMPK alleviated kidney function and preserved tubular structure. These data support AMPK activation as a novel therapeutic approach for AKI.
Funding
- Commercial Support – Janssen R&D