Extracellular cold-inducible RNA-binding protein (eCIRP), a novel inflammatory biomarker to assess ischemia-reperfusion injuries, and protection conferred by mild therapeutic hypothermia - 25/06/22
, Delphine Baetz 2, Bruno Pillot 2, Christelle Leon 2, Maud Rabeyrin 3, Gabriel Bidaux 2, Laurent Juillard 4, Fitsum Guebre-Egziabher 4, Laurent Argaud 1, Martin Cour 1, Sandrine Lemoine 5
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Résumé |
Introduction |
Ischemia-reperfusion (IR) leads to systemic inflammation. Mild therapeutic hypothermia (mTH) has been suggested to bring protection against IR lesions. However, mTH remains limited to intensive care units (ICU) after resuscitated cardiac arrest (rCA) and is not currently used in nephrology. Extracellular cold-inducible RNA-binding protein (eCIRP) is a pro-inflammatory cytokine that can be secreted during stress situations such as hypoxia.
Objective |
To test if eCIRP plasma level is correlated to renal IR injuries in mice with or without mTH.
Method |
A 20-minutes bilateral renal ischemia by clamping (or a sham procedure) was conducted on C57BL6 mice with core body temperature maintained at 37°C (normothermia) or 34°C (mTH). Plasma eCIRP, IL-6, IL-10 and urea were dosed 2h and 24h after reperfusion. Acute tubular necrosis (ATN) was scored (from 0 to 4) on histological exam of kidneys at 24h.
Results |
Bilateral renal ischemia in mice was associated with AKI compared to sham as soon as 2h after reperfusion (median urea 18.7 vs. 11.7mmol/L, P=0.02) and more severe 24h after reperfusion (median urea 60.8 vs. 6.2mmol/L, P=0.004), and with ATN 24h after reperfusion (median histological score 2.23 vs. 0.80, P<0.001). Plasma eCIRP levels were significantly increased by renal IR 24h after reperfusion compared to sham (median 123.1 vs. 21.5pg/mL, P=0.03). Renal IR also led to a peak of IL-6 secretion 2h after reperfusion, and of IL-10 secretion 24h after reperfusion. We showed a correlation between eCIRP and urea levels 2h after reperfusion (Spearman r=0.60, P=0.007) and 24h after reperfusion (Spearman r=0.84, P<0.001), and with ATN score (Spearman r=0.65, P<0.001). The use of mTH during renal ischemia was followed by a significantly reduced plasma urea (median 22.7mmol/L, P=0.001), ATN score (median 1.45, P=0.03) and eCIRP elevation (median 60.8pg/mL, P=0.03) 24h after reperfusion, and an inhibition of IL-6 and IL-10 secretion (Fig. 1).
Conclusion |
Plasma eCIRP increases 24h after renal IR in mice and is correlated to AKI and ATN. The use of mTH during ischemia alleviates eCIRP elevation in parallel of renal IR injury and inflammation. We aim to measure eCIRP level in ICU after rCA (i.e. global IR) at admission, and at day 1 and 3 to confirm our results in a cohort of 33 patients in order to test if eCIRP is correlated to relevant clinical and biological outcomes, such as AKI and its severity.
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Vol 14 - N° 2
P. 169-170 - juin 2022 Retour au numéro
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