Therapeutic efficacy of naloxone hydrochloride combined with hemoperfusion in toxic acute renal failure via the oxidative stress/Nrf2 pathway

Abstract: Background: Toxic acute renal failure (ARF) involves severe oxidative stress. The Nrf2 pathway is a key antioxidant defense mechanism. Objectives: To investigate whether naloxone combined with hemoperfusion alleviates oxidative injury via Nrf2 activation in toxic ARF. Methods: In this single-center retrospective cohort study at Qiqihar Medical University Hospital, 67 patients were enrolled through medical record screening. The control group (n=39) received hemoperfusion alone; the observation group (n=28) received additional intravenous naloxone (0.8 mg bolus + 2.0 mg/24 h infusion for 7 days). Renal function and oxidative markers were assessed before treatment, at 24 h and day 7. Multivariate regression analysis was used to adjust for confounding factors. Separately, 30 rats were randomized into control, model and treatment groups (n=10 each). The treatment group received intraperitoneal naloxone (1.0 mg/kg) plus simulated hemoperfusion. Results: After adjusting for baseline imbalances, combined therapy was independently associated with significant reductions in Scr and BUN in patients (adjusted β = -8.52, 95% CI: -12.37 to -4.67, P < 0.001) and with significant improvements in renal function and histopathology in rats. Combined therapy decreased tubular injury markers (β2-MG, KIM-1, NGAL, L-FABP) in rats. Mechanistically, it was associated with activation of the Nrf2/HO-1/NQO1 pathway, enhanced SOD activity and reduced MDA levels. Improvements were time-dependent (24 h to day 7). Conclusions: Naloxone combined with hemoperfusion activates the Nrf2 pathway, attenuates oxidative stress and improves renal function in toxic acute renal failure.