Kidney Week

Abstract: SA-PO0247

Greater AKI Severity Is Associated with Reduced Renal Hypoxia During Early Recovery

Session Information

• AKI: Mechanisms - Cell Signaling
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Rogers, Joshua, East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Joshua Rogers, MBA

• Payne, Christopher Bennett, East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Christopher Bennett Payne

• Joseph, Christopher Antony, East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Christopher Antony Joseph

• Shaw, Makayla Ann, East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Makayla Ann Shaw

• Priyadarshi, Shreya, East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Shreya Priyadarshi

• Rashid, Zara F., East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Zara F. Rashid

• Chopde, Purva R., Illinois Institute of Technology Armour College of Engineering, Chicago, Illinois, United States

Purva R. Chopde, MS

• Williamson, Geoffrey A., Illinois Institute of Technology Armour College of Engineering, Chicago, Illinois, United States

Geoffrey A. Williamson, PhD

• Griffin, Karen A., Loyola University Chicago Stritch School of Medicine, Chicago, Illinois, United States

Karen A. Griffin, MD, FASN

• O'Connor, Paul, Augusta University, Augusta, Georgia, United States

Paul O'Connor, PhD

• Polichnowski, Aaron J., East Tennessee State University James H Quillen College of Medicine, Johnson City, Tennessee, United States

Aaron J. Polichnowski, PhD

Background

Acute kidney injury (AKI) is commonly thought to promote persistent renal hypoxia during recovery due to microvascular dysfunction and impaired oxygen delivery. However, severe ischemic injury also markedly reduces glomerular filtration rate and tubular transport, potentially lowering renal oxygen consumption. Therefore, this study examined the relationship between ischemia-reperfusion (IR) injury severity and renal hypoxyprobe staining during recovery from AKI in uninephrectomized rats.

Methods

Male Sprague-Dawley rats underwent right uninephrectomy with concurrent sham IR (n=7), 17.5-min left renal IR (n=8), or 35-min left renal IR (n=7). Plasma creatinine (P_Cr) was measured at 2 days following surgery and used as an index of AKI severity. On day 6, rats received pimonidazole (Hypoxyprobe; 60 mg/kg, ip). Kidneys were harvested on day 7 for hypoxyprobe immunohistochemistry and blinded semiquantitative scoring. Scores ranged from preserved organized corticomedullary staining (3) to markedly reduced/disorganized corticomedullary staining (1). Group comparisons were analyzed using Kruskal-Wallis testing with Dunn’s post hoc analysis. Associations between injury severity and hypoxyprobe score were assessed using linear regression. Data are mean±SE and P<0.05 was considered statistically significant.

Results

Hypoxyprobe scores were reduced (P<0.05) in rats exposed to 35-min IR (1.6±0.2) compared to 17.5-min IR (2.9±0.2) and sham IR (3.0±0) groups (Fig 1A). Greater functional impairment following AKI was strongly associated with lower hypoxyprobe scores at day 7 (r²=0.71, p<0.0001, Fig 1B).

Conclusion

Severe IR injury was associated with reduced renal hypoxyprobe staining 1 week following AKI, whereas mild injury was associated with preserved corticomedullary staining patterns. These findings suggest that severe AKI may reduce renal hypoxia during the early recovery period, potentially due to reduced tubular oxygen utilization.

Funding

• NIDDK Support