Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors.

https://www.mdpi.com/2076-3921/10/2/313/pdf

Functions of ROS in Macrophages and Antimicrobial Immunity

Ferroptosis is a new type of oxidative regulated cell death (RCD) driven by iron-dependent lipid peroxidation. As major sites of iron utilization and master regulators of oxidative metabolism, mitochondria are the main source of reactive oxygen species (ROS) and, thus, play a role in this type of RCD. Ferroptosis is, indeed, associated with severe damage in mitochondrial morphology, bioenergetics, and metabolism. Furthermore, dysregulation of mitochondrial metabolism is considered a biochemical feature of neurodegenerative diseases linked to ferroptosis. Whether mitochondrial dysfunction can, per se, initiate ferroptosis and whether mitochondrial function in ferroptosis is context-dependent are still under debate. Cancer cells accumulate high levels of iron and ROS to promote their metabolic activity and growth. Of note, cancer cell metabolic rewiring is often associated with acquired sensitivity to ferroptosis. This strongly suggests that ferroptosis may act as an adaptive response to metabolic imbalance and, thus, may constitute a new promising way to eradicate malignant cells. Here, we review the current literature on the role of mitochondria in ferroptosis, and we discuss opportunities to potentially use mitochondria-mediated ferroptosis as a new strategy for cancer therapy.

Ferroptosis and Cancer: Mitochondria Meet the “Iron Maiden” Cell Death

Pannexin 1 mediates ferroptosis that contributes to renal ischemia/reperfusion injury.

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries.

Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental and conserved mechanism is based on an excess of ROS which attacks biomembranes, propagates lipid peroxidation chain reactions, and subsequently induces different types of cell death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how ROS propagate lipid peroxidation chain reactions and how the products of lipid peroxidation initiate apoptosis and autophagy in current models. We also discussed the mechanism of lipid peroxidation during ferroptosis, and we summarized lipid peroxidation in pathological conditions of critical illness. We aim to bring a more global and integrative sight to know how different ROS-induced lipid peroxidation occurs among apoptosis, autophagy, and ferroptosis.

/pdf/reactive-oxygen-species-induced-lipid-peroxidation-in-2sa2bbdea5.pdf

Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis.

ABSTRACT Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between mitochondria oxidative stress, ROS production and mitophagy are intimately interwoven, and these processes are all involved in various pathological conditions of acute kidney injury (AKI). The elimination of damaged mitochondria through mitophagy in mammals is a complicated process which involves several pathways. Furthermore, the interplay between mitophagy and different types of cell death, such as apoptosis, pyroptosis and ferroptosis in kidney injury is unclear. Here we will review recent advances in our understanding of the relationship between ROS and mitophagy, the different mitophagy pathways, the relationship between mitophagy and cell death, and the relevance of these processes in the pathogenesis of AKI. Abbreviations: AKI: acute kidney injury; AMBRA1: autophagy and beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer 1; BAX: BCL2 associated X, apoptosis regulator; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BH3: BCL2 homology domain 3; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CASP1: caspase 1; CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced acute kidney injury; CISD1: CDGSH iron sulfur domain 1; CL: cardiolipin; CNP: 2’,3’-cyclic nucleotide 3’-phosphodiesterase; DNM1L/DRP1: dynamin 1 like; E3: enzyme 3; ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 domain containing 1; G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase 3 beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor 1 subunit alpha; HUWE1: HECT, UBA and WWE domain containing 1; IL1B: interleukin 1 beta; IMM: inner mitochondrial membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion injury; LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: mitochondrial permeability transition; MUL1: mitochondrial E3 ubiquitin protein ligase 1; mtROS: mitochondrial ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin domain containing 3; NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer mitochondrial membrane; OPA1: OPA1 mitochondrial dynamin like GTPase; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PINK1: PTEN induced kinase 1; PLSCR3: phospholipid scramblase 3; PMP: peptidase, mitochondrial processing; PRDX: peroxiredoxin; PRKN: parkin RBR E3 ubiquitin protein ligase; RPTC: rat proximal tubular cells; ROS: reactive oxygen species; SLC7A11/xCT: solute carrier family 7 member 11; SOD: superoxide dismutase; SOR: superoxide reductase; SQSTM1/p62: sequestosome 1; TCA: tricarboxylic acid; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin containing protein.

https://www.tandfonline.com/doi/pdf/10.1080/15548627.2022.2084862?needAccess=true

Mitochondria ROS and mitophagy in acute kidney injury

Downregulation of TIMP2 attenuates sepsis-induced AKI through the NF-κb pathway.

Objective: We investigated the epidemiology, risk factors, and predictive parameters for ischemic or hemorrhagic stroke-associated acute kidney injury (AKI) and mortality in a general intensive care unit (ICU) in China. Methods: During 5 years, 479 stroke patients were screened, and 381 were enrolled. AKI was diagnosed within 7 days after ICU admission, based on the Kidney Disease Improving Global Outcomes criteria. Risk factors of AKI were assessed by Logistic regression analyses, and the predictive biomarkers for AKI were determined using receiver operating characteristic (ROC) curves. Also examined were factors influencing 28-day mortality, using Cox regression analyses and Kaplan-Meier curves. ­Results: Among all, 115 (30.18%) patients developed AKI. Multivariate regression analyses revealed that the following features at ICU admission significantly increased the risk of developing AKI: an increased National Institutes of Health Stroke Scale score (OR 1.136, p < 0.001) and Acute Physiology and Chronic Health Evaluation II score (OR 1.107, p = 0.042); hypertension (OR 2.346, p = 0.008); use of loop diuretics (OR 1.961, p = 0.032); and higher serum cystatin C (sCysC; OR 8.156, p = 0.001). The area under the ROC curves for predicting AKI using sCysC was 0.772, slightly better than that of other biomarkers. The sCysC ≥0.93 mg/L (hazard ratio 1.844, p = 0.004) significantly predicted 28-day mortality. Conclusions: Among stroke patients in ICU, we identified significant risk factors of stroke-associated AKI. Serum CysC level at ICU admission was an important biomarker for predicting AKI and 28-day mortality.

Incidence, Risk factors, and Biomarkers Predicting Ischemic or Hemorrhagic Stroke Associated Acute Kidney Injury and Outcome: A Retrospective Study in a General Intensive Care Unit.

Lianjiu Su

Papers

Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis.

Pannexin 1 mediates ferroptosis that contributes to renal ischemia/reperfusion injury.

Mitochondria ROS and mitophagy in acute kidney injury

Downregulation of TIMP2 attenuates sepsis-induced AKI through the NF-κb pathway.

Incidence, Risk factors, and Biomarkers Predicting Ischemic or Hemorrhagic Stroke Associated Acute Kidney Injury and Outcome: A Retrospective Study in a General Intensive Care Unit.