The incidence of acute kidney injury (AKI) continues to rise in both men and women. Although creatinine levels return to normal quicker in females following AKI than in males, it is unclear whether subclinical renal injury persists in young females post-AKI. This study tested the hypothesis that AKI results in subclinical renal injury in females despite plasma creatinine returning to sham levels. 12-13-week-old female Sprague-Dawley (SD) rats were randomized to sham or 45-minute warm bilateral ischemia-reperfusion surgery as an experimental model of ischemic AKI. Rats were euthanized 1, 3-, 7-, 14-, or 30-days post-AKI/sham. Plasma creatinine, cystatin C, kidney injury molecule 1 (KIM-1), and NGAL were quantified via assay kits or immunoblotting. Kidneys were processed for histological analysis to assess tubular injury and fibrosis and electron microscopy to examine mitochondrial morphology. Immunoblots on kidney homogenates were performed to determine oxidative stress and apoptosis. Plasma creatinine levels were greater 24 hours post-AKI but returned to sham control levels 3 days post-AKI. However, cystatin C, KIM-1, and NGAL were greater 30 days post-AKI compared to sham. Tubular injurytubulointerstitial fibrosis, and mitochondrial dysfunction were all greater in 30-day post-AKI rats compared to sham. Additionally, 30 days post-AKI rats had greater p-JNK expression and lower antioxidant enzyme GPx1 and catalase levels compared to sham. AKI resulted in greater expression of cleaved caspase 3, TUNEL+ cells, and caspase 9 than sham. Despite the normalization of creatinine levels, our data support the hypothesis that subclinical renal injury persists following ischemia-reperfusion injury in young female rats.
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Research Article|
February 04 2025
Persistent subclinical renal injury in female rats following renal ischemia reperfusion injury
Jennifer C. Sullivan;
Augusta University Medical College of Georgia, Augusta, Georgia, United States
* Corresponding Author; email: [email protected]
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Desmond Moronge;
Desmond Moronge
Augusta University, Augusta, Georgia, United States
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Hannah Godley;
Hannah Godley
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Victor Ayulo;
Victor Ayulo
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Elisabeth Mellott;
Elisabeth Mellott
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Mona Elgazzaz;
Mona Elgazzaz
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Gibson Cooper;
Gibson Cooper
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Riyaz Mohamed;
Riyaz Mohamed
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Safia Ogbi;
Safia Ogbi
Augusta University Medical College of Georgia, Augusta, Georgia, United States
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Jessica L Faulkner
Jessica L Faulkner
Augusta University, Augusta, Georgia, United States
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Publisher: Portland Press Ltd
Received:
August 26 2024
Revision Received:
January 17 2025
Accepted:
February 03 2025
Online ISSN: 1470-8736
Print ISSN: 0143-5221
Funding
Funding Group:
- Award Group:
- Funder(s):
- Award Id(s): R01DK134695
- Principal Award Recipient(s): Jennifer C.Sullivan
- Funder(s):
Copyright 2025 The Author(s)
2025
This is an Accepted Manuscript; not the final Version of Record. Archiving permitted only in line with the archiving policy of Portland Press Limited.
Clin Sci (Lond) (2025) CS20241851.
Article history
Received:
August 26 2024
Revision Received:
January 17 2025
Accepted:
February 03 2025
Citation
Jennifer C. Sullivan, Desmond Moronge, Hannah Godley, Victor Ayulo, Elisabeth Mellott, Mona Elgazzaz, Gibson Cooper, Riyaz Mohamed, Safia Ogbi, Jessica L Faulkner; Persistent subclinical renal injury in female rats following renal ischemia reperfusion injury. Clin Sci (Lond) 2025; CS20241851. doi: https://doi.org/10.1042/CS20241851
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