The angiotensin II receptor antagonist telmisartan promotes renal recovery after ischemia-reperfusion injury by reprogramming fatty acid metabolism
Current clinical guidelines recommend withholding renin-angiotensin-aldosterone system (RAAS) inhibitors during acute kidney injury (AKI) due to concerns over impaired glomerular perfusion. However, their potential to mitigate post-AKI inflammation and fibrosis remains unexplored. We hypothesized th...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2026
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| In: |
American journal of physiology. Cell physiology
Year: 2026, Volume: 330, Issue: 3, Pages: 695-705 |
| ISSN: | 1522-1563 |
| DOI: | 10.1152/ajpcell.00801.2025 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1152/ajpcell.00801.2025 Verlag, kostenfrei, Volltext: https://journals-physiology-org.ezproxy.medma.uni-heidelberg.de/doi/full/10.1152/ajpcell.00801.2025 
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| Author Notes: | Chang Chu, Denis Delić, Zeyu Zhang, Shufei Zeng, Mohamed M. S. Gaballa, Thomas Klein, Saban Elitok, Carl-Friedrich Hocher, Bernhard K. Krämer, Xin Chen, and Berthold Hocher |
| Summary: | Current clinical guidelines recommend withholding renin-angiotensin-aldosterone system (RAAS) inhibitors during acute kidney injury (AKI) due to concerns over impaired glomerular perfusion. However, their potential to mitigate post-AKI inflammation and fibrosis remains unexplored. We hypothesized that telmisartan, an angiotensin II receptor blocker (ARB) with reported peroxisome proliferator-activated receptor gamma (PPAR-γ) activity, would enhance recovery from ischemic AKI. Male Wistar rats were subjected to unilateral nephrectomy and 45-min ischemia in the contralateral kidney, or sham surgery. Animals were randomized to receive telmisartan (3 mg/kg/day) or placebo for 10 days, starting 1 wk before injury. Telmisartan treatment significantly accelerated the recovery of renal function and attenuated tubular necrosis, inflammation, and the expression of injury biomarkers. At the whole kidney tissue level at 72 h postischemia-reperfusion injury (IRI), bulk RNA-sequencing compared with healthy control mice without IRI revealed apparent broad metabolic dysfunction, with suppression of fatty acid oxidation and mitochondrial pathways, which may reflect both injury-driven changes in cellular composition and transcriptional regulation within surviving cells. These transcriptomic findings 72 h after IRI were significantly blunted or even abolished by telmisartan. These treatment effects did not show evidence of direct PPAR-γ pathway activation. This study suggests that the metabolic modulatory effects of certain angiotensin II receptor blockers may provide therapeutic benefit during the recovery phase of AKI, independent of direct PPAR-γ signaling. - NEW & NOTEWORTHY RAAS inhibitors are routinely withheld during acute kidney injury (AKI) because of concerns about impaired renal perfusion. Contrary to this dogma, we show that telmisartan enhances renal recovery following ischemia-reperfusion injury. Transcriptomic analyses reveal that telmisartan restores fatty acid oxidation and mitochondrial-peroxisomal lipid metabolism, key pathways suppressed in AKI. These findings suggest that selected RAAS inhibitors may actively promote post-AKI metabolic recovery rather than merely pose hemodynamic risk. |
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| Item Description: | Online veröffentlicht: 27. Februar 2026 Gesehen am 21.04.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1522-1563 |
| DOI: | 10.1152/ajpcell.00801.2025 |