Evidence map›Paper›PMID 42649526›Full record

ArticleLaboratory animal research2026

Optimised murine model of influenza-induced respiratory sepsis for studying acute kidney injury.

Yaqing Jiao, Will Lung Chan, Yuee Cai, Arthur Chuxi Liu, Yilin Zhang, John M Nicholls, Timothy H Rainer

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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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5 · Who and what money

Authors and funding

7 authors.

Yaqing JiaoDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Will Lung ChanDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Yuee CaiDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Arthur Chuxi LiuDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Yilin ZhangDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
John M NichollsDepartment of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Timothy H RainerDepartment of Emergency Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. thrainer@hku.hk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AKIInfluenzaMurine modelNGALRespiratory sepsis

Identifiers

PMID42649526
PMCPMC13508304

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