scholarly journals Association of post‐reperfusion syndrome and ischemia‐reperfusion injury with acute kidney injury after liver transplantation

2020 ◽  
Vol 64 (6) ◽  
pp. 742-750
Author(s):  
Kazuaki Tokodai ◽  
Claudia Lannsjö ◽  
Felicia Kjaernet ◽  
Antonio Romano ◽  
Anna Januszkiewicz ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury

scholarly journals Cell Death Patterns Due to Warm Ischemia or Reperfusion in Renal Tubular Epithelial Cells Originating from Human, Mouse, or the Native Hibernator Hamster

Biology ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 48 ◽  
Author(s):  
Theodoros Eleftheriadis ◽  
Georgios Pissas ◽  
Georgia Antoniadi ◽  
Vassilios Liakopoulos ◽  
Ioannis Stefanidis
Keyword(s):  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Cell Death ◽  
Epithelial Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Human Cells ◽  
Tubular Epithelial Cells

Ischemia–reperfusion injury contributes to the pathogenesis of many diseases, with acute kidney injury included. Hibernating mammals survive prolonged bouts of deep torpor with a dramatic drop in blood pressure, heart, and breathing rates, interspersed with short periods of arousal and, consequently, ischemia–reperfusion injury. Clarifying the differences under warm anoxia or reoxygenation between human cells and cells from a native hibernator may reveal interventions for rendering human cells resistant to ischemia–reperfusion injury. Human and hamster renal proximal tubular epithelial cells (RPTECs) were cultured under warm anoxia or reoxygenation. Mouse RPTECs were used as a phylogenetic control for hamster cells. Cell death was assessed by both cell imaging and lactate dehydrogenase (LDH) release assay, apoptosis by cleaved caspase-3, autophagy by microtubule-associated protein 1-light chain 3 B II (LC3B-II) to LC3B-I ratio, necroptosis by phosphorylated mixed-lineage kinase domain-like pseudokinase, reactive oxygen species (ROS) fluorometrically, and lipid peroxidation, the end-point of ferroptosis, by malondialdehyde. Human cells died after short periods of warm anoxia or reoxygenation, whereas hamster cells were extremely resistant. In human cells, apoptosis contributed to cell death under both anoxia and reoxygenation. Although under reoxygenation, ROS increased in both human and hamster RPTECs, lipid peroxidation-induced cell death was detected only in human cells. Autophagy was observed only in human cells under both conditions. Necroptosis was not detected in any of the evaluated cells. Clarifying the ways that are responsible for hamster RPTECs escaping from apoptosis and lipid peroxidation-induced cell death may reveal interventions for preventing ischemia–reperfusion-induced acute kidney injury in humans.

scholarly journals CBX7 suppression prevents ischemia-reperfusion injury-induced endoplasmic reticulum stress through the Nrf-2/HO-1 pathway

2020 ◽  
Vol 318 (6) ◽  
pp. F1531-F1538
Author(s):  
Ye Zhang ◽  
Jian-Jian Zhang ◽  
Xiu-Heng Liu ◽  
Lei Wang
Keyword(s):  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Translation Initiation Factor ◽  
Heme Oxygenase 1

Renal ischemia-reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of chromobox 7 (CBX7) could attenuate renal I/R injury in vivo and in vitro as well as the potential mechanisms. Adult male mice were subjected to right renal ischemia and reperfusion for different periods, both with and without the CBX7 inhibitor UNC3866. In addition, human kidney cells (HK-2) were subjected to a hypoxia/reoxygenation (H/R) process for different periods, both with or without the CBX7 inhibitor or siRNA for CBX7. The results showed that expression of CBX7, glucose regulator protein-78 (GRP78), phosphorylated eukaryotic translation initiation factor-2α (p-eIF2α), and C/EBP homologous protein (CHOP) were increased after extension of I/R and H/R periods. Moreover, overexpression of CBX7 could elevate the expression of CBX7, GRP78, p-eIF2α, and CHOP. However, CBX7 inhibition with either UNC3866 or genetic knockdown led to reduced expression of GRP78, p-eIF2α, and CHOP through nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 activation in I/R and H/R injury. Furthermore, ML385, the Nrf2 inhibitor, could elevate endoplasmic reticulum stress levels, abrogating the protective effects of UNC3866 against renal I/R injury. In conclusion, our results demonstrated that CBX7 inhibition alleviated acute kidney injury by preventing endoplasmic reticulum stress via the Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury.

scholarly journals New mouse model of chronic kidney disease transitioned from ischemic acute kidney injury

2019 ◽  
Vol 317 (2) ◽  
pp. F286-F295 ◽  
Author(s):  
Jin Wei ◽  
Jie Zhang ◽  
Lei Wang ◽  
Shan Jiang ◽  
Liying Fu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Reperfusion Injury ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury

Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD), which is closely associated with the severity of AKI. However, the underlying mechanisms for the AKI to CKD transition remain unclear. Several animal models with AKI to CKD transition have been generated and widely used in research; however, none of them exhibit the typical changes in glomerular filtration rate or plasma creatinine, the hallmarks of CKD. In the present study, we developed a novel model with a typical phenotype of AKI to CKD transition in C57BL/6 mice. In this model, life-threatening ischemia-reperfusion injury was performed in one kidney, whereas the contralateral kidney was kept intact to maintain animal survival; then, after 2 wk of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was removed. Animals of this two-stage unilateral ischemia-reperfusion injury model with pedicle clamping of 21 and 24 min exhibited an incomplete recovery from AKI and subsequent progression of CKD with characteristics of a progressive decline in glomerular filtration rate, increase in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis. In conclusion, a new model of the AKI to CKD transition was generated in C57BL/6 mice.

MO420ROLE OF IL-6 ON ACUTE KIDNEY INJURY (AKI) DEVELOPMENT AFTER LIVER TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Francesca Tinti ◽  
Martina Colicchio ◽  
Stefano Ginanni Corradini ◽  
Gianluca Mennini ◽  
Massimo Rossi ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Kidney Injury ◽  
Growth Factor ◽  
Reperfusion Injury ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Liver Graft

Abstract Background and Aims Acute kidney injury (AKI) post-liver transplantation is a frequent complication with an incidence up to 70%, requiring renal replacement therapy in about 25% of transplant patients. AKI in patients with normal renal function is a recognized risk factor (FR) of chronic renal failure (CKD) de novo, associated with a 4.5 times greater mortality at 5 years post-transplant. Pathogenesis of AKI is multifactorial. Beyond the classical pre-transplant risk factors, the hypoxia of the graft and the ischemia-reperfusion injury (IRI) have recently been recognized to exert a pathogenetic role with specific mechanisms. It has been recently demonstrated in experimental setting that ischemic tissues put in place protective mechanisms in response to hypoxia aimed at increasing the release of oxygen with the activation of angiogenesis mediated by the expression of factors induced by hypoxia (HIF)-1-alpha. HIF1-alfa has been shown to promote cell survival under hypoxic conditions by switching metabolism from oxidative to glycolytic, by affecting the production of ATP to prevent excessive mitochondrial generation of reactive oxygen species, by promoting secondary release of vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-ß1), with following activation of inflammatory cytokines responsible for systemic inflammatory response syndrome (SIRS). Tumor necrosis factor-α, IL-1 and IL-6 are the most important cytokines released in IRI and seem to play a pivotal role in the onset of AKI in SIRS and sepsis. The development of AKI after hypoxia/ischemia of the graft, as observed more frequently in the population of recipients from donors after cardiocirculatory death (DCD) compared to donation after brain death (DBD), confirms this pathogenetic mechanism. Aim of the study is to evaluate AKI occurrence among liver transplanted patients and its relationship with IRI and cytokines systemic release. Method Data of 78 patients (62 males, 79.5%) undergone liver transplantation (2007-2011) were retrieved. Results The following clinical investigations were performed: AKI patients demonstrated a progressive increasing of IL-6 after liver transplantation (AKI 34.4-37.8-88.2 ng/ml vs no AKI 30.5-21.6-23.3 ng/ml). Conclusion Patients who experienced greater ischaemia-reperfusion injury of the liver graft developed more frequently AKI. Patients with AKI experienced an increased release and circulation of IL-6, that probably is involved in AKI development with interesting implications in future therapy.

scholarly journals Urine podoplanin heralds the onset of ischemia-reperfusion injury of the kidney

2019 ◽  
Vol 316 (5) ◽  
pp. F957-F965 ◽  
Author(s):  
Vivek Kasinath ◽  
Osman Arif Yilmam ◽  
Mayuko Uehara ◽  
Merve Yonar ◽  
Liwei Jiang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
The United States ◽  
Positive Signal ◽  
Current Standard ◽  
Common Causes ◽  
Standard Assay

Ischemia-reperfusion injury represents one of the most common causes of acute kidney injury, a serious and often deadly condition that affects up to 20% of all hospitalized patients in the United States. However, the current standard assay used universally for the diagnosis of acute kidney injury, serum creatinine, does not detect renal damage early in its course. Serendipitously, we found that the immunofluorescent signal of the constitutive podocyte marker podoplanin fades in the glomerulus and intensifies in the tubulointerstitial compartment of the kidney shortly after ischemia-reperfusion injury in 8- to 10-wk-old male C57Bl/6j mice. Therefore, we sought to define the appearance and course of the podoplanin-positive signal in the kidney after ischemia-reperfusion injury. The tubulointerstitial podoplanin-positive signal increased as early as 2 h but persisted for 7 days after ischemia-reperfusion injury. In addition, the strength of this tubulointerstitial signal was directly proportional to the severity of ischemia, and its location shifted from the tubules to interstitial cells over time. Finally, we detected podoplanin in the urine of mice after ischemia, and we observed that an increase in the urine podoplanin-to-creatinine ratio correlated strongly with the onset of renal ischemia-reperfusion injury. Our findings indicate that the measurement of urine podoplanin harbors promising potential for use as a novel biomarker for the early detection of ischemia-reperfusion injury of the kidney.

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