Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis.
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ABSTRACT:
SUBMITTER: Pan XW
PROVIDER: S-EPMC7106051 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis.
Pan Xiu-Wu XW Xu Da D Zhang Hao H Zhou Wang W Wang Lin-Hui LH Cui Xin-Gang XG
Intensive care medicine 20200331 6
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Project description: Not available
| S-EPMC7529117 | biostudies-literature
Project description:BackgroundNovel coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread, affecting >10 million cases worldwide. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and primarily manifesting as an acute respiratory failure with interstitial and alveolar pneumonia, it can also affect multiple organs. Kidney involvement was underestimated in early reports and its role remains controversial. The aim of this study was to analyse the role of kidney damage in COVID-19 outcome.MethodsThis is a prospective cohort study of 1603 consecutive patients admitted in a University Reference Hospital in the heart of the European outbreak.ResultsMedian age was 64 years, 40.4% were female, 15.2% presented diabetes mellitus, 35.7% hypertension and 20.3% obesity. On admission, the prevalence of elevated serum creatinine (sCr), proteinuria, leucocyturia and haematuria were 21.0, 37.8, 31.8 and 45.6%, respectively. In total, 43.5% of those with an elevated sCr had previous chronic kidney disease (CKD) and 11.4% of those with normal sCr developed an in-hospital acute kidney injury (AKI); 17 patients needed acute haemodialysis; and 197 patients died during hospitalization. Cox proportional hazard regression confirmed that elevated baseline sCr [hazard ratio (95% confidence interval) 2.40 (1.79-3.22)], previous CKD [1.59 (1.06-2.37)], haematuria [1 + 1.68 (0.92-3.06), 2-3 + 2.69 (1.49-4.87)] and in-hospital AKI [1.50 (0.92-2.44)] were independent risk factors for in-hospital death after adjusting for age, sex and comorbidity.ConclusionThe prevalence of acute and chronic kidney disease on admission and in-hospital AKI is higher than previously reported in Wuhan, and is associated with high in-hospital mortality. We should increase our awareness towards kidney involvement and design specific strategies for management of COVID-19 in these patients.
| S-EPMC7462722 | biostudies-literature
Project description:Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs, and the therapeutic measures are still limited. This study aims to investigate crucial genes correlated with AKI, and their potential functions, which might contribute to a better understanding of AKI pathogenesis. The high-throughput data GSE52004 and GSE98622 were downloaded from Gene Expression Omnibus; four group sets were extracted and integrated. Differentially expressed genes (DEGs) in the four group sets were identified by limma package in R software. The overlapping DEGs among four group sets were further analyzed by the VennDiagram package, and their potential functions were analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database. Furthermore, the protein-protein interaction (PPI) network was constructed by STRING, and the functional modules of the PPI network were filtered by MCODE and ClusterOne in Cytoscape. Hub genes of overlapping DEGs were identified by Cyto-Hubba and cytoNCA. The expression of 35 key genes was validated by quantitative real-time PCR (qRT-PCR). Western blot and immunofluorescence were performed to validate an important gene Egr1. A total of 722 overlapping DEGs were differentially expressed in at least three group sets. These genes mainly enriched in cell proliferation and fibroblast proliferation. Additionally, 5 significant modules and 21 hub genes, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln were screened by analyzing the PPI networks. The 5 significant modules were mainly enriched in complement and coagulation cascades and Metabolic pathways, and the top 21 hub genes were mainly enriched in positive regulation of cell proliferation. Through validation, Krt20 were identified as the top 1 upregulated genes with a log2 (fold change) larger than 10 in all these 35 genes, and 21 genes were validated as significantly upregulated; Egr1 was validated as an upregulated gene in AKI in both RNA and protein level. In conclusion, by integrated analysis of different high-throughput data and validation by experiment, several crucial genes were identified in AKI, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln. These genes were very important in the process of AKI, which could be further utilized to explore novel diagnostic and therapeutic strategies.
| S-EPMC7247857 | biostudies-literature
Project description:Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome-corona virus (SARS-CoV-2), a beta coronavirus, mainly involves the respiratory tract, and the clinical features simulate to a severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) of the past. The genome of the SARS-CoV-2, isolated from a cluster-patient with a typical pneumonia after visiting Wuhan, had 89% nucleotide identitical with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. It enters the respiratory tract through angiotensin converting enzyme-2 (ACE2) receptors on alveoli. It may induce lung injury through direct cytopathic effect, involving effector T cells or causing sepsis and inducing cytokine storm. With a similar mechanism, it can cause acute kidney injury (AKI). The overall incidence of AKI is 5.1%, and AKI is an independent risk factor for mortality. The hazard ratio of death increases with the increasing severity of AKI. Management of COVID-19 with AKI is primarily supportive care, and at present, there are no evidence based effective antivirals for the treatment.
| S-EPMC7470203 | biostudies-literature
Project description:As of 15 August 2020, Coronavirus disease 2019 (COVID-19) has been reported in >21 million people world-wide and is responsible for more than 750,000 deaths. The occurrence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be as high as 43%. This is comparable to AKI in other forms of pneumonia requiring hospitalization, as well as in non-infectious conditions like cardiac surgery. The impact of AKI on COVID-19 outcomes is difficult to assess at present but, similar to other forms of sepsis, AKI is strongly associated with hospital mortality. Indeed, mortality is reported to be very low in COVID-19 patients without AKI. Given that AKI contributes to fluid and acid-base imbalances, compromises immune response and may impair resolution of inflammation, it seems likely that AKI contributes to mortality in these patients. The pathophysiologic mechanisms of AKI in COVID-19 are thought to be multifactorial including systemic immune and inflammatory responses induced by viral infection, systemic tissue hypoxia, reduced renal perfusion, endothelial damage and direct epithelial infection with Severe Acute Respiratory Syndrome Coronavirus 2. Mitochondria play a central role in the metabolic deregulation in the adaptive response to the systemic inflammation and are also found to be vital in response to both direct viral damage and tissue reperfusion. These stress conditions are associated with increased glycolysis and reduced fatty acid oxidation. Thus, there is a strong rationale to target AKI for therapy in COVID-19. Furthermore, many approaches that have been developed for other etiologies of AKI such as sepsis, inflammation and ischemia-reperfusion, have relevance in the treatment of COVID-19 AKI and could be rapidly pivoted to this new disease.
| S-EPMC7665651 | biostudies-literature
Project description:We uesd single-cell transcriptome sequencing technology to sequence the mononuclear phagocytes in the mice kidney, blood and spleen after acute kidney injury, and comprehensively describe characteristics of mononuclear phagocytes.
2022-02-09 | GSE174324 | GEO
Project description:ImportanceCOVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown.ObjectiveTo assess long-term kidney outcomes of patients who had COVID-19-associated AKI.Design, setting, and participantsThis was a retrospective longitudinal multicenter cohort study conducted in a large hospital system using electronic health records data on adult hospitalized patients with AKI and COVID-19 or other illnesses. Included patients were hospitalized during the COVID-19 pandemic (March 2020-June 2022), were screened for SARS-CoV-2, had AKI, and survived to discharge, or had been hospitalized during the 5 years before the pandemic (October 2016-January 2020), had a positive influenza A or B test result, had AKI, and survived to discharge. Patients were followed up for a maximum of 2 years after hospital discharge. Data analyses were performed from December 2022 to November 2023.ExposureCOVID-19 and influenza.Main outcomes and measuresThe primary outcome was major adverse kidney events (MAKE), defined as a composite of mortality and worsened kidney function (estimated glomerular filtration rate [eGFR] decline by ≥25% from discharge eGFR or kidney failure requiring dialysis). Multivariable time-to-event analyses were performed to compare MAKE between individuals with COVID-AKI and those who had AKI associated with other illnesses hospitalized during the same period. For further comparison, this outcome was assessed for a historic cohort of patients with influenza-associated AKI.ResultsThe study cohort included 9624 hospitalized patients (mean [SD] age, 69.0 [15.7] years; 4955 [51.5%] females) with AKI, including 987 patients with COVID-AKI, 276 with influenza-associated AKI, and 8361 with AKI associated with other illnesses (other-AKI). Compared with the other 2 groups, patients with COVID-19-associated AKI were slightly younger in age, had a higher baseline eGFR, worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stay. Compared with the other-AKI group, the COVID-AKI group had lower MAKE (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.59-0.75) due to lower all-cause mortality (aHR, 0.31; 95% CI, 0.24-0.39) and lower rates of worsened kidney function (aHR, 0.78; 95% CI, 0.69-0.88).Conclusions and relevanceThe findings of this multicenter cohort study indicate that survivors of hospitalization with COVID-AKI experience lower rates of MAKE, long-term kidney function decline, and mortality compared with patients with AKI associated with other illnesses.
| S-EPMC10897825 | biostudies-literature
Project description:Studies in humans and animal models have demonstrated that acute kidney injury (AKI) has a significant effect on the function of extrarenal organs. The combination of AKI and lung dysfunction is associated with 80% mortality; the lung, because of its extensive capillary network, is a prime target for AKI-induced effects. The study presented here tested the hypothesis that AKI leads to a vigorous inflammatory response and produces distinct genomic signatures in the kidney and lung. In a murine model of ischemic AKI, prominent global transcriptomic changes and histologic injury in both kidney and lung tissues were identified. These changes were evident at both early (6 h) and late (36 h) timepoints after 60-min bilateral kidney ischemia and were more prominent than similar timepoints after sham surgery or 30 min of ischemia. The inflammatory transcriptome (109 genes) of both organs changed with marked similarity, including the innate immunity genes Cd14, Socs3, Saa3, Lcn2, and Il1r2. Functional genomic analysis of these genes suggested that IL-10 and IL-6 signaling was involved in the distant effects of local inflammation, and this was supported by increased serum levels of IL-10 and IL-6 after ischemia-reperfusion. In summary, this is the first comprehensive analysis of concomitant inflammation-associated transcriptional changes in the kidney and a remote organ during AKI. Functional genomic analysis identified potential mediators that connect local and systemic inflammation, suggesting that this type of analysis may be a useful discovery tool for novel biomarkers and therapeutic drug development.
| S-EPMC2391061 | biostudies-literature
Project description:Acute kidney injury (AKI) is common among hospitalized patients with coronavirus disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. An improved knowledge of the pathology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who develop AKI during COVID-19. In this review, we summarize the published cases and case series of various kidney pathologies seen with COVID-19. Both live kidney biopsies and autopsy series suggest acute tubular injury as the most commonly encountered pathology. Collapsing glomerulopathy and thrombotic microangiopathy are other encountered pathologies noted in both live and autopsy tissues. Other rare findings such as anti-neutrophil cytoplasmic antibody vasculitis, anti-glomerular basement membrane disease and podocytopathies have been reported. Although direct viral infection of the kidney is possible, it is certainly not a common or even widespread finding reported at the time of this writing (November 2020).
| S-EPMC7929005 | biostudies-literature
Project description:Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.
| S-EPMC8256398 | biostudies-literature