Temporary bilateral clamping of renal arteries induces ischemia–reperfusion: A new pig model of acute kidney injury using total intravenous anesthesia

Abstract

Ischemia-reperfusion (IR) is a leading cause of acute kidney injury (AKI), and pigs are commonly used in preclinical AKI models. However, existing models often vary in the methods used to induce ischemia, and the resulting AKI tends to be mild-to-moderate. Moreover, follow-up is often performed under volatile anesthesia, which, in contrast to total intravenous anesthesia (TIVA), can induce malignant hyperthermia and cause hemodynamic instability. Here we present a novel surgical model of IR-induced AKI using bilateral renal artery clamping under TIVA. Anesthesia was induced via TIVA with diazepam, ketamine, and morphine. After retroperitoneal exposure, the renal arteries were isolated and clamped with a plastic tube for 90 min, followed by 8 h of reperfusion. The IR group (n = 6) was compared with a Sham group (n = 5) that underwent the same procedure without IR. The IR group developed moderate-to-severe AKI as evidenced by reduced glomerular filtration, a 158% increase in plasma creatinine versus 21% in the Sham group, and elevated neutrophil gelatinase-associated lipocalin levels (+280% in IR vs. 0% in Sham), indicating tubular injury. Histopathology confirmed these findings. Thus, this preclinical model successfully induced moderate-to-severe AKI in pigs. The TIVA anesthetic protocol offered several advantages compared to halogenated gas anesthesia.