Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment

Peerapornratana, Sadudee; Manrique‐Caballero, Carlos L.; Gómez, Hernando; Kellum, John A.

doi:10.1016/j.kint.2019.05.026

Cited by 719 publications

(603 citation statements)

References 217 publications

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“…The activation of these pathways ultimately leads to an elevation in the transcription level of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, as well as HMGB1. 43 TNF-α, IL-1β, and IL-6 are early pro-inflammatory mediators; whereas the high mobility group box 1 (HMGB1) is regarded as a late pro-inflammatory mediator in the sepsis pathogenesis. 44 Diminishing the level of HMGB1 has been regarded as a broad therapeutic approach for sepsis.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein protects against lipopolysaccharide‐induced sepsis and alleviates inflammatory responses in mice

et al. 2020

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Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)‐induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty‐four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation‐related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule‐1) in the septic mice. OLE pretreatment ameliorated LPS‐induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and inflammation‐related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS‐induced sepsis in mice.

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Section: Discussionmentioning

confidence: 99%

Oleuropein protects against lipopolysaccharide‐induced sepsis and alleviates inflammatory responses in mice

et al. 2020

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“…It is highly probable that this imbalance could contribute to the renal dysfunction observed in severe patients with COVID-19, which could also be accompanied by a decrease in ACE2 activity (8,46,60). It has become clearer that sepsis-associated AKI is multifactorial, involving the kidney inflammatory response, microcirculatory dysfunction, and metabolic reprogramming with mitochondrial injury (55). These mechanisms are compatible with our current understanding of SARS-CoV-2 infection and biology, supporting the prevailing hypothesis that COVID-19-associated AKI takes place in a severe disease scenario with a complex pathophysiological network, but, in contrast to other SARSrelated viruses (14), SARS-CoV-2 direct infection of the proximal epithelium could importantly support a causal relationship in AKI development (66).…”

Section: Kidney Abnormalities Induced By Sars-cov-2: Potential Involvmentioning

confidence: 99%

Is the kidney a target of SARS-CoV-2?

Martínez‐Rojas

Vega-Vega

Bobadilla

2020

American Journal of Physiology-Renal Physiology

186

159

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The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.

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“…Sepsis is a type of life-threatening organ dysfunction caused by dysregulation of the host response to infection (Coopersmith et al, 2018;Kushimoto et al, 2019). Discovery of biomarkers for sepsis-induced AKI could contribute to early diagnosis of the disease (Peerapornratana et al, 2019). This study identified a set of 56 statistically relevant upregulated and 67 downregulated proteins from rats with CLP-induced AKI using MS.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Spatiotemporal Urine Protein Dynamics to Identify New Biomarkers for Sepsis-Induced Acute Kidney Injury

Long

Chen

et al. 2020

Front. Physiol.

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Acute kidney injury (AKI) is a frequent complication of sepsis and contributes to increased mortality. Discovery of reliable biomarkers could enable identification of individuals with high AKI risk as well as early AKI detection and AKI progression monitoring. However, the current methods are insensitive and non-specific. This study aimed to identify new biomarkers through label-free mass spectrometry (MS) analysis of a sepsis model induced by cecal ligation and puncture (CLP). Urine samples were collected from septic rats at 0, 3, 6, 12, 24, and 48 h. Protein isolated from urine was subjected to MS. Immunoregulatory biological processes, including immunoglobin production and wounding and defense responses, were upregulated at early time points. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 77 significantly changed pathways. We further examined the consistently differentially expressed proteins to seek biomarkers that can be used for early diagnosis. Notably, the expression of PARK7 and CDH16 were changed in a continuous manner and related to the level of Scr in urine from patients. Therefore, PARK7 and CDH16 were confirmed to be novel biomarkers after validation in sepsis human patients. In summary, our study analyzed the proteomics of AKI at multiple time points, elucidated the related biological processes, and identified novel biomarkers for early diagnosis of sepsis-induced AKI, and our findings provide a theoretical basis for further research on the molecular mechanisms.

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Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment

Cited by 719 publications

References 217 publications

Oleuropein protects against lipopolysaccharide‐induced sepsis and alleviates inflammatory responses in mice

Oleuropein protects against lipopolysaccharide‐induced sepsis and alleviates inflammatory responses in mice

Is the kidney a target of SARS-CoV-2?

Analysis of Spatiotemporal Urine Protein Dynamics to Identify New Biomarkers for Sepsis-Induced Acute Kidney Injury

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