Kidney Week

Abstract: SA-PO0266

Synchronization of 12-Hour Circatidal Rhythm Protects the Hibernating Ground Squirrel Kidney Through Repeated Cycles of Warm Reperfusion

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

• Gillen, Austin Edward, University of Colorado System, Denver, Colorado, United States

Austin Edward Gillen, PhD

• Jain, Swati, University of Colorado System, Denver, Colorado, United States

Swati Jain, PhD

• Orlicky, David J., University of Colorado System, Denver, Colorado, United States

David J. Orlicky, PhD

• Martin, Sandy, University of Colorado System, Denver, Colorado, United States

Sandy Martin, PhD

• Jani, Alkesh, University of Colorado System, Denver, Colorado, United States

Alkesh Jani, MD

Background

Hibernating 13-lined ground squirrel (TLGS) kidneys undergo repeated multiday cycles of torpor at 4^○ C with blood flow 1% of normal, followed by rapid warm reperfusion during arousal. SCr increases ~ 3-fold but, remarkably, TLGS kidneys are protected.

Methods

To understand mechanisms of protection from AKI, we analyzed pathology specimens and RNA-seq data from 32 TLGS kidneys at 6 timepoints based on seasonal and torpor-arousal cycle (TAC)physiology .

Results

Immune infiltration and cell damage were absent after repeated TAC. Differentially-expressed genes revealed both seasonal and TAC specific gene expression dynamics and molecular mechanisms that prevent damage and allow full recovery during each 12-hour warming.

Conclusion

We show the hibernator fails to develop histological or molecular characteristics of AKI and CKD even after numerous TAC that alternate multiday periods of blood flow at 1% of normal at 4°C with rapid reperfusion and rewarming to 37°C. The hibernating TLGS thus avoids AKI and CKD during each TAC and seasonally including widespread cell death, immune infiltration, activation and fibrosis. As with mouse IRI, the arousing hibernator initiates an immediate early gene expression program (IER) upon warm reperfusion. In the hibernator, this IER does not precipitate gene expression of maladaptive repair, immune activation and fibrosis. Rather, the IER synchronize 12-hour rhythm genes that have been seasonally primed for rapid repair and replication. The efficient unfolding of this program during each TAC leads to adaptive repair, restoring proteostasis and cell-type specific function.

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Funding

• NIDDK Support