CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury

Liu, Wenyan; Yang, Yan; Han, Dan; Li, Yongxin; Wang, Qian; Li, Jing; Liu, Fengfeng; Zheng, Xinglong

doi:10.1055/s-0041-1730450

Cited by 5 publications

(4 citation statements)

References 29 publications

(26 reference statements)

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“…Furthermore, in studies involving CIRP knockout mice undergoing renal I/R, a reduction in inflammation and injury severity was observed (35). A relationship between eCIRP and AKI was demonstrated in a study where patients undergoing cardiac surgery and whose serum had higher levels of circulating eCIRP showed an increased risk of AKI in the postoperative period (47). In addition, eCIRP has been shown to increase other DAMPs such as HMGB1, further augmenting the inflammatory activity (16,35).…”

Section: Discussionmentioning

confidence: 99%

Novel Ps-Ome Mirna130b-3p Reduces Inflammation and Injury and Improves Survival After Renal Ischemia-Reperfusion Injury

Vazquez,

Sfakianos,

Coppa

et al. 2023

Shock

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Introduction Acute kidney injury (AKI) is a prevalent medical disorder characterized by a sudden decline in kidney function, often because of ischemia-reperfusion events. It is associated with significant chronic complications, and currently available therapies are limited to supportive measures. Extracellular cold-inducible RNA-binding protein (eCIRP) has been identified as a mediator that potentiates inflammation following ischemia-reperfusion injury. However, it has been discovered that miRNA 130b-3p acts as an endogenous inhibitor of eCIRP. To address the inherent instability of miRNA in vivo, a chemically modified miRNA mimic called PS-OME miR130 was developed. We hypothesize that administration of PS-OME miR130 following renal ischemia/reperfusion (I/R) can lead to reduced inflammation and injury in a murine model of AKI. Methods C57BL/6 male mice underwent renal I/R by clamping of bilateral renal hilum for 30 min or sham operation. Immediately following closure, mice were intravenously administered vehicle (PBS) or PS-OME miR130 at a dose of 12.5 nmol/mouse. Blood and kidneys were collected after 24 h for further analysis. Separately, mice underwent renal I/R and administered vehicle or treatment and, survival was monitored for 10 days. Results Following renal I/R, mice receiving vehicle showed a significant increase in serum markers of kidney injury and inflammation including BUN, NGAL, KIM-1 and IL-6. Following treatment with PS-OME miR130, these markers were significantly decreased. Kidney tissue mRNA expression for injury and inflammation markers including NGAL, KIM-1, KC, and MIP-2 were increased after renal I/R, however, these markers showed a significant reduction with PS-OME miR130 treatment. Histologically, treatment with PS-OME miR130 showed a significant decrease in neutrophil infiltration and injury severity score, and decreased apoptosis. In the 10-day survival study, mice in the treatment group showed a significant reduction in mortality as compared to vehicle group. Conclusion In a murine renal I/R model, the administration of PS-OME miR130, a direct eCIRP antagonistic miRNA mimic, resulted in the reduction of kidney inflammation and injury, and improved survival. PS-OME miR130 holds promise to be developed as novel therapeutic for AKI as an adjunct to the standard of care.

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Section: Discussionmentioning

confidence: 99%

Novel Ps-Ome Mirna130b-3p Reduces Inflammation and Injury and Improves Survival After Renal Ischemia-Reperfusion Injury

Vazquez,

Sfakianos,

Coppa

et al. 2023

Shock

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“…However, there are few studies focusing on the relationship between BCDIMs and pAKI. Considering that systematic inflammation is involved in the onset of pAKI ( 9 , 16 ), we speculated that these inflammatory markers might be risk factors for pAKI and could predict pAKI onset.…”

Section: Introductionmentioning

confidence: 99%

“…Surgical complications, such as acute kidney injury (AKI), are closely related to the poor prognosis of patients who underwent TAAD surgery (7). Insufficient tissue perfusion, stress response, oxidative stress, and systematic inflammation caused by TAAD and surgery can contribute to the onset of postoperative AKI (pAKI) (8,9). Zhang et al (10) and Wang et al (11) reported that pAKI was significantly associated with worse short-term and long-term mortality of patients who underwent TAAD surgery.…”

Section: Introductionmentioning

confidence: 99%

The predictive values of monocyte–lymphocyte ratio in postoperative acute kidney injury and prognosis of patients with Stanford type A aortic dissection

Chen¹,

Dong²,

Cheng³

et al. 2023

Front. Immunol.

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ObjectivesPostoperative acute kidney injury (pAKI) is a serious complication of Stanford type A aortic dissection (TAAD) surgery, which is significantly associated with the inflammatory response. This study aimed to explore the relationship between blood count-derived inflammatory markers (BCDIMs) and pAKI and to construct a predictive model for pAKI.MethodsPatients who underwent TAAD surgery were obtained from our center and the Medical Information Mart for Intensive Care (MIMIC)-IV database. The differences in preoperative BCDIMs and clinical outcomes of patients with and without pAKI were analyzed. Logistic regression was used to construct predictive models based on preoperative BCDIMs or white cell counts (WCCs). The performance of the BCDIMs and WCCs models was evaluated and compared using the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), Hosmer–Lemeshow test, calibration plot, net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA). The Kaplan–Meier curves were applied to compare the survival rate between different groups.ResultsThe overall incidence of pAKI in patients who underwent TAAD surgery from our center was 48.63% (124/255). The presence of pAKI was associated with longer ventilation time, higher incidence of cerebral complications and postoperative hepatic dysfunction, and higher in-hospital mortality. The results of the logistic regression indicated that the monocyte–lymphocyte ratio (MLR) was an independent risk factor for pAKI. The BCDIMs model had good discriminating ability, predictive ability, and clinical utility. In addition, the performance of the BCDIMs model was significantly better than that of the WCCs model. Analysis of data from the MIMIC-IV database validated that MLR was an independent risk factor for pAKI and had predictive value for pAKI. Finally, data from the MIMIC-IV database demonstrated that patients with a high MLR had a significantly poor 28-day survival rate when compared to patients with a low MLR.ConclusionOur study suggested that the MLR is an independent risk factor for pAKI. A predictive model based on BCDIMs had good discriminating ability, predictive ability, and clinical utility. Moreover, the performance of the BCDIMs model was significantly better than that of the WCCs model. Finally, a high MLR was significantly associated with poor short-term survival of patients who underwent TAAD surgery.

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“…Our previous study demonstrated that CIRP serum levels were significantly elevated after CPB, which was closely related to the occurrence of AKI [ 18 ]. Therefore, we hypothesized that excessive CIRP is secreted into the circulation during CPB, which may subsequently induce oxidative stress and disturb mitochondrial dynamics to promote CSA-AKI.…”

Section: Introductionmentioning

confidence: 99%

Change in Oxidative Stress and Mitochondrial Dynamics in Response to Elevated Cold-Inducible RNA-Binding Protein in Cardiac Surgery-Associated Acute Kidney Injury

Zheng

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common yet serious complication that is closely related to cardiopulmonary bypass (CPB). Extracellular cold-inducible RNA-binding protein (eCIRP) can mediate aseptic inflammation and trigger intracellular oxidative stress. In the present study, expression of serum CIRP was significantly elevated post-CPB ( 785.0 ± 640.5 pg/mL vs. 149.5 ± 289.1 pg/mL, P < 0.001 ) and was positively correlated with CPB duration ( r = 0.502 , P < 0.001 ). Patients with high expression of CIRP had higher risks of postoperative AKI than patients with low CIRP expression (OR: 1.67, 95% CI 1.04-2.68). In a rat CPB model, the serum CIRP concentration increased significantly after CPB. Similarly, the levels of Scr and BUN significantly increased 4 hours after CPB. KIM-1 and NGAL mRNA levels in the CPB group were 8.2 and 4.3 times higher than the sham group, respectively. In addition, the levels of inflammatory cell infiltration, oxidative stress, and apoptosis in the renal tissue of the CPB group were significantly higher compared to the sham group. The expression levels of serum inflammatory factors at 4 hours post-CPB were also increased. Administration of recombinant human CIRP protein promoted the expression of NADPH oxidase via the TLR-4/MyD88 pathway, aggravated intracellular oxidative stress, mediated mitochondrial dynamics disorder, and eventually increased apoptosis in HK-2 cells. However, the CIRP inhibitor C23 improved the CIRP-mediated oxidative stress and mitochondrial dysfunction in both rat and cell models. In summary, elevated CIRP could mediate oxidative stress and mitochondrial dynamics in the kidney to promote CSA-AKI.

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CIRP Secretion during Cardiopulmonary Bypass Is Associated with Increased Risk of Postoperative Acute Kidney Injury

Cited by 5 publications

References 29 publications

Novel Ps-Ome Mirna130b-3p Reduces Inflammation and Injury and Improves Survival After Renal Ischemia-Reperfusion Injury

Novel Ps-Ome Mirna130b-3p Reduces Inflammation and Injury and Improves Survival After Renal Ischemia-Reperfusion Injury

The predictive values of monocyte–lymphocyte ratio in postoperative acute kidney injury and prognosis of patients with Stanford type A aortic dissection

Change in Oxidative Stress and Mitochondrial Dynamics in Response to Elevated Cold-Inducible RNA-Binding Protein in Cardiac Surgery-Associated Acute Kidney Injury

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