Perfluorocarbon solutions limit tubular epithelial cell injury and promote CD133+ kidney progenitor differentiation: potential use in renal assist devices for sepsis-associated acute kidney injury and multiple organ failure

Abstract Background Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. Results In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. Conclusions This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.

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Severe Acute Kidney Injury and Multiple Organ Failure in a 17-Day-Old Newborn: When Pathology Makes the Difference

Canadian Journal of Kidney Health and Disease ◽

10.1177/2054358118804834 ◽

2018 ◽

Vol 5 ◽

pp. 205435811880483 ◽

Cited By ~ 1

Author(s):

Marie-Michèle Gaudreault-Tremblay ◽

Catherine Litalien ◽

Natalie Patey ◽

Aicha Merouani

Keyword(s):

Acute Kidney Injury ◽

Multiple Organ Failure ◽

Organ Failure ◽

Kidney Injury ◽

Multiple Organ ◽

The Difference

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Acute kidney injury and posttrauma multiple organ failure

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e318244869b ◽

2012 ◽

Vol 72 (2) ◽

pp. 373-380 ◽

Cited By ~ 34

Author(s):

Max V. Wohlauer ◽

Angela Sauaia ◽

Ernest E. Moore ◽

Clay Cothren Burlew ◽

Anirban Banerjee ◽

...

Keyword(s):

Acute Kidney Injury ◽

Multiple Organ Failure ◽

Organ Failure ◽

Kidney Injury ◽

Multiple Organ

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Primary Injuries and Secondary Organ Failures in Trauma Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

Scientifica ◽

10.1155/2014/235215 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Sigrid Beitland ◽

Ingrid Os ◽

Kjetil Sunde

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Multiple Organ Failure ◽

Replacement Therapy ◽

Organ Failure ◽

Kidney Injury ◽

Multiple Organ ◽

Trauma Patients ◽

Organ Failures

Background. Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is a severe complication in trauma patients. The aim of the study was to assess primary traumatic injuries and secondary organ failures in severe posttraumatic AKI.Methods. Retrospective review of adult trauma patients admitted to the trauma centre at Oslo University Hospital Ullevål. Injury severity score (ISS) was used to assess the severity of primary injuries, and sequential organ failure assessment (SOFA) score was utilized to measure secondary organ failures.Results. Forty-two (8%) of 506 trauma patients admitted to intensive care unit developed AKI treated with CRRT, whereof 40 (95%) suffered blunt trauma mechanisms. Patients had extensive primary organ injuries with median (interquartile range) ISS 36 (27–49). The majority of the patients had respiratory (93% intubated) and cardiovascular (67% with inotropic and/or vasoactive medication) failure within 24 hours after admission. AKI was often part of multiple organ failure, most frequently respiratory and cardiovascular failure, affecting 33 (75%) and 30 (71%) of the patients, respectively.Conclusion. Trauma patients with AKI undergoing CRRT often had severe primary injuries due to blunt trauma. Most of them suffered from secondary multiple organ failure concomitant to AKI.

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