Abstract: FR-PO0166
Kidney Cortical Macrophages Reduce Lysosome Stress Markers and Improve Kidney Recovery Following Murine Ischemic AKI
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
- Wu, Chia-Chun, Duke University School of Medicine, Durham, North Carolina, United States
- Chen, Yanting, Duke University School of Medicine, Durham, North Carolina, United States
- Lu, Xiaohan, Duke University School of Medicine, Durham, North Carolina, United States
- Crowley, Steven D., Duke University School of Medicine, Durham, North Carolina, United States
- Privratsky, Jamie R., Duke University School of Medicine, Durham, North Carolina, United States
Background
Chronic kidney disease (CKD) is a significant health and economic burden. Impaired recovery from acute kidney injury (AKI) contributes to CKD progression. We have shown that a cortical F4/80hi resident macrophage population limits septic AKI but the role of F4/80hi macrophages after ischemic AKI is unknown. We hypothesized that F4/80hi macrophages would improve kidney recovery following ischemic AKI.
Methods
Transgenic mice: F4/80 Macrophage KO (MKO) (CD11c-Cre(+) / CX3CR1dtr/wt ) and littermate F4/80 macrophage WT (MWT) mice underwent F4/80 macrophages via diphtheria toxin starting at day 3 after AKI. Model: unilateral ischemia/reperfusion (I/R) with delayed contralateral nephrectomy one day before harvest on days 7, 14, and 28. Primary outcome: serum creatinine(sCr). Secondary outcomes: serum BUN and RT-PCR mRNA measurements of kidney injury markers Havcr1/KIM1 and fibrosis markers fibronectin and α-SMA. Exploratory analysis: mRNA/protein levels of pro-inflammatory cytokines, lysosome markers in whole kidneys. Statistics: unpaired T-tests for two-group comparisons and two-way ANOVA with Bonferroni post-hoc for 2 independent variables.
Results
Compared to F4/80 MWT mice, F4/80 MKO mice had significantly impaired kidney recovery between day 7 and day 28 following I/R as determined by sCr (p<0.05) and BUN (p<0.01) and increased kidney injury markers (KIM-1, p<0.05; NGAL, p<0.01) and fibrosis markers (a-SMA, p<0.01; fibronectin, p<0.0001) at day 28 post I/R. F4/80 MKO mice also showed increased expression of lysosome marker LAMP2 and decreased mitochondrial transcription factor A (Tfam).
Conclusion
Depletion of cortical F4/80 macrophages limits kidney functional recovery following ischemic AKI and is associated markers of increased lysosome accumulation and decreased mitochondrial biogenesis. We are actively exploring the mechanistic underpinnings through which F4/80 macrophages play a crucial role in supporting lysosome and mitochondrial function in kidney tubules to promote cellular repair after injury.
Funding
- NIDDK Support