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 that telmisartan, an angiotensin II receptor blocker (ARB) with reported PPAR-γ activity, would enhance recovery from ischemic AKI. Male Wistar rats were subjected to unilateral nephrectomy and 45-minute ischemia in the contralateral kidney, or sham surgery. Animals were randomized to receive telmisartan (3 mg/kg/day) or placebo for 10 days, starting one week 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 post‑IRI, bulk RNA‑sequencing compared to 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. This 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.