ArticleLaboratory animal research2026
Optimised murine model of influenza-induced respiratory sepsis for studying acute kidney injury.
Article in Laboratory animal research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundViral respiratory sepsis, driven by influenza and COVID-19, is increasingly prominent clinically. However, there is a lack of preclinical models that reliably replicate its associated acute kidney injury (AKI), a major contributor to morbidity and mortality. To address this gap, we refined an established model of influenza-induced respiratory sepsis by administering graded intranasal H1N1 A/PR/8/34 doses (3.7 × 10¹, 3.7 × 10³, and 3.7 × 10⁴ TCID₅₀) in male BALB/c mice. We defined humane endpoints at ≥ 30% body weight loss, monitored clinical severity, weight, and glycaemia daily for 14 days, and assessed multi-organ dysfunction via serum biochemistry, histopathology, renal qPCR, and longitudinal serum neutrophil gelatinase-associated lipocalin (NGAL) ELISA.
resultsThe 3.7 × 10⁴ TCID₅₀ dose yielded 66.7% mortality by day 8, with a peak clinical score (MSS) of 10, > 30% weight loss, and hypoglycaemia (blood glucose < 70 mg/dL). Infected mice exhibited dose-dependent multi-organ dysfunction, with substantial elevations in serum creatinine (median: 204 [IQR: 142-600] µmol/L), bilirubin (40.62 [IQR: 29.3-124.9] µmol/L), and creatine phosphokinase (CPK) (9822 [IQR: 1,272-11,352] U/L). Renal NGAL expression increased up to 7-fold, aligning with rising serum creatinine levels and histopathological evidence of glomerular enlargement and tubular degeneration. Serum NGAL showed early elevation (up to 4,990 ng/mL on day 2) in severely affected mice, with levels remaining 5.7-7.6-fold higher than sham controls through days 4-8.
conclusionsThis exploratory study describes an optimised murine model of influenza-induced respiratory sepsis that develops biochemical and histopathological evidence of AKI. Early elevation of serum NGAL was observed in severely affected animals, supporting its potential as a candidate early biomarker. The model provides a useful platform for further mechanistic and therapeutic investigation in viral respiratory infection-associated AKI.
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