Renohepatic crosstalk: does acute kidney injury cause liver dysfunction?

Lane, Katie; Dixon, Jonathon; MacPhee, Iain; Philips, Barbara J.

doi:10.1093/ndt/gft091

Cited by 80 publications

(74 citation statements)

References 111 publications

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“…Accumulating clinical evidence has identified a close relationship between renal injury and injuries to other organ systems, including heart, lung, and liver 3. Indeed, impaired liver function is often seen in patients with acute kidney injury (AKI) 4, 5. In addition, in‐hospital death is more likely in patients with AKI and liver failure than in those with AKI alone 6.…”

Section: Introductionmentioning

confidence: 99%

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

Zhao

Huang

Alam

et al. 2018

American Journal of Transplantation

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Clinical evidence has indicated a possible link between renal injury and remote liver injury. We investigated whether extracellular histone mediates remote hepatic damage after renal graft ischemia–reperfusion injury, while vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown‐Norway renal graft was stored in 4°C preservation solution for 24 hours and then transplanted into a Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery. Prolonged cold ischemia in renal grafts enhanced liver injury 24 hours after engraftment. Caspase‐1, ASC, NLRP3, and AIM2 expressions in hepatocyte, CD68+‐infiltrating macrophages, tissue, and serum interleukin‐1β and ‐18 were greatly elevated, indicating that pyroptosis occurred in the liver and resulted in acute liver functional impairment. Blocking the caspase‐1 pathway decreased the number of necrotic hepatocytes. VEGF treatment suppressed the hepatocyte pyroptosis and liver function was partially restored. Our data suggested that renal allograft ischemia–reperfusion injury is likely associated with acute liver damage due to hepatocyte pyroptosis induced by histone and such injury may be protected by VEGF administration. VEGF, therefore, may serve as a new strategy against other remote organ injuries related to renal transplantation.

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Section: Introductionmentioning

confidence: 99%

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

Zhao

Huang

Alam

et al. 2018

American Journal of Transplantation

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show abstract

“…On the contrary, the role of AKI in liver failure is less clear. Some studies suggest a modification of liver metabolism after AKI [35]. In a case-control study in ICU, an increased 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase gene activation in AKI patients compared to control patients without AKI was observed [36].…”

Section: Human Studiesmentioning

confidence: 96%

A Role of Remote Organs Effect in Acute Kidney Injury Outcome

Dépret

Prudhomme²,

Legrand³

2017

Nephron

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Acute kidney injury (AKI) has been associated with both short- and long-term outcomes. To date, there is still a debate whether the increase risk of morbidity and mortality is directly due to AKI occurrence. There is, however, a potential causal impact of AKI on outcome, but evidence of this association is yet lacking. The hypothesis of remote organ damage and dysfunction (heart, lung, liver, brain, etc.) has emerged over the last decade and may explain the reason for the potential negative impact of AKI on outcome. The aim of this review was to describe findings concerning the remote effect of AKI in animal models and human studies.

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“…However, RRT is proven to carry dramatic risks for adverse patient outcome leading to the reactive oxygen species as well as, hemodynamic instability and nutrients loss during RRT and inflammatory reaction 64,65 . Depend on the mechanisms mentioned before; several complex pathways are involved in the remote organs injury during AKI including pulmonary, cardiovascular, gastrointestinal, hepatobiliary, and neuromuscular 56,[66][67][68][69] . Remote impact on the heart Acute kidney injury (AKI) may result in acute cardiac disorder via some mechanisms including: and TNFα resulting from increased production and impaired clearance.…”

Section: Remote Organ Injury Following Renal I/r Injurymentioning

confidence: 99%

“…Evidence showed that AKI has significant effect on liver inflammatory response and drug as well as other nutrient metabolism, and even patient outcomes 67 .…”

Section: Remote Impact On the Livermentioning

confidence: 99%

Most Important Cellular Changes Involved in Renal Ischemia Reperfusion Injury and the Consequent Impact on Selected Remote Organs

Khalifa

Ghoneim²

2018

UJPR

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Because of the high rate of baseline oxygen use by renal cells, kidney is highly influenced by obstruction of arterial blood inflow and subsequent shortage of the received oxygen, this condition is known as Ischemic injury. There are many clinical settings associated with unavoidable ischemic state such as kidney transplantation, partial nephrectomy or suprarenal procedures of the aorta. During ischemia many cellular changes occur including vascular congestion and adhesion of inflammatory cells to the endothelium with subsequent infiltration into the kidney tissue. Following ischemia, a phase known as Reperfusion begins and involves a return of blood and oxygen supply to micro vessels. Reperfusion was expected to restore the damage occurred during the ischemic phase, paradoxically, reperfusion leads to more congestion, red cells trapping and excessive generation of reactive oxygen species (ROS), which can oxidatively modify significantly every type of biomolecule, thereby inducing cell dysfunction and induce reperfusion injury. Ischemia reperfusion injury (IRI) is also related to a phenomenon called Remote Organ Injury (ROI) in which the damaging effect induced by I/R is not only restricted to the tissue that undergoing the initial ischemia but also it leads to injury to remote organs such as the liver, lung, gut. ROI usually occurs by the same mechanisms seen in the local injury induced by I/R including the generation of ROS, leukocytes, and inflammatory mediators (e.g; TNF-α). These substances are directly released from the primary injured tissue or indirectly from activated leukocytes or other inflammatory cells causing organ dysfunctions in distant organs.

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Renohepatic crosstalk: does acute kidney injury cause liver dysfunction?

Cited by 80 publications

References 111 publications

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia–reperfusion injury in rats

A Role of Remote Organs Effect in Acute Kidney Injury Outcome

Most Important Cellular Changes Involved in Renal Ischemia Reperfusion Injury and the Consequent Impact on Selected Remote Organs

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