Optimised murine model of influenza-induced respiratory sepsis for studying acute kidney injury
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Updated: Aug 28, 2026
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Yaqing Jiao1, Will Lung Chan1, Yuee Cai1
1Department of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Background:
Viral 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.
Results:
The 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.
Conclusions:
This 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.
