scholarly journals Effect of ondansetron on reducing ICU mortality in patients with acute kidney injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaojiang Guo ◽  
Xiguang Qi ◽  
Peihao Fan ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Severity Of Illness ◽  
Icu Mortality ◽  
Chi Square ◽  
Beneficial Effects ◽  
Real World Evidence ◽  
Gene Expression Signatures ◽  
Chi Square Test

AbstractThe purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.

scholarly journals Effect of Ondansetron on Reducing ICU Mortality in Patients with Acute Kidney Injury

2021 ◽  
Author(s):  
Xiaojiang Guo ◽  
Xiguang Qi ◽  
Peihao Fan ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Severity Of Illness ◽  
Icu Mortality ◽  
Chi Square ◽  
Beneficial Effects ◽  
Real World Evidence ◽  
Gene Expression Signatures ◽  
Chi Square Test

Abstract The purpose of this study is to identify medications with potentially beneficial effects on decreasing mortality in patients with acute kidney injury (AKI) while in the intensive care unit (ICU). We used logistic regression to investigate associations between medications received and ICU mortality in patients with AKI in the MIMIC III database. Drugs associated with reduced mortality were then validated using the eICU database. Propensity score matching (PSM) was used for matching the patients’ baseline severity of illness followed by a chi-square test to calculate the significance of drug use and mortality. Finally, we examined gene expression signatures to explore the drug’s molecular mechanism on AKI. While several drugs demonstrated potential beneficial effects on reducing mortality, most were used for potentially fatal illnesses (e.g. antibiotics, cardiac medications). One exception was found, ondansetron, a drug without previously identified life-saving effects, has correlation with lower mortality among AKI patients. This association was confirmed in a subsequent analysis using the eICU database. Based on the comparison of gene expression signatures, the presumed therapeutic effect of ondansetron may be elicited through the NF-KB pathway and JAK-STAT pathway. Our findings provide real-world evidence to support clinical trials of ondansetron for treatment of AKI.

scholarly journals Influence of Erythrocyte Transfusion on the Risk of Acute Kidney Injury after Cardiac Surgery Differs in Anemic and Nonanemic Patients

2011 ◽  
Vol 115 (3) ◽  
pp. 523-530 ◽  
Author(s):  
Keyvan Karkouti ◽  
Duminda N. Wijeysundera ◽  
Terrence M. Yau ◽  
Stuart A. McCluskey ◽  
Christopher T. Chan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Propensity Score ◽  
Conditional Logistic Regression ◽  
Kidney Injury ◽  
Erythrocyte Transfusion ◽  
Preoperative Anemia ◽  
Chi Square ◽  
Propensity Score Methods ◽  
Chi Square Test

Background Acute kidney injury (AKI) after cardiac surgery is a major health issue. Two important risk factors for AKI are preoperative anemia and perioperative erythrocyte transfusion, and elucidating their relationship may help in devising preventive strategies. Methods In this cohort study of 12,388 adults who underwent cardiac surgery with cardiopulmonary bypass and received three units or less of erythrocytes on the day of surgery, the authors used propensity score methods and conditional logistic regression to explore the relationship between preoperative anemia (hemoglobin less than 12.5 g/dL), erythrocyte transfusion on the day of surgery, and AKI (more than 50% decrease in estimated glomerular filtration rate from preoperative to postoperative day 3-4). Results AKI occurred in 4.1% of anemic patients (n = 94/2,287) and 1.6% of nonanemic patients (n = 162 of 10,101) (P < 0.0001). In the 2,113 propensity-score matched pairs, anemic patients had higher AKI rates than nonanemic patients (3.8% vs. 2.0%; P = 0.0007). AKI rates increased in direct proportion to the amount of erythrocytes transfused, and this increase was more pronounced in anemic patients: in anemic patients, the rate increased from 1.8% among those not transfused to 6.6% among those transfused three units (chi-square test for trend P < 0.0001), whereas in nonanemic patients, it increased from 1.7% among those not transfused to 3.2% among those transfused three units (chi-square test for trend P = 0.1). Conclusions Anemic patients presenting for cardiac surgery are more susceptible to transfusion-related AKI than nonanemic patients. Interventions that reduce perioperative transfusions may protect anemic patients against AKI.

scholarly journals Post Operative Acute Kidney Injury after HPB Surgeries – A Single Centre Retrospective Analysis

2020 ◽  
Author(s):  
Bhavin B. Vasavada ◽  
Hardik Patel
Keyword(s):  
Acute Kidney Injury ◽  
Univariate Analysis ◽  
Kidney Injury ◽  
Acute Kidney Injury Network ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Chi Square ◽  
Causative Factors ◽  
Chi Square Test ◽  
Grade Increase

Aim: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in hepatopancreaticobiliary (HPB) surgeries. Material and Methods: All the HPB surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and fisher t test wherever approptiate and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant. Results: We performed 195 HPB surgeries between April 2018 to March 2020, Which included 114 biliary surgeries, 57 liver surgeries and 23 pancreas surgeries. 10 patients developed Acute Kidney Injuries. (AKI) On Univariate analysis AKI was associated with open surgeries, intra operative hypotension and liver surgeries, higher ASA grade, increase operative time, more blood products used, higher CDC grade of surgery and more hospital stay before diagnosis of AKI. However on multivariate analysis only higher ASA score independently predicted Acute Kidney Injury. (p=0.003, odds ratio 15.659, 95% confidence interval 2.54-93.36). AKI was also significantly associated with mortality. (p <0.0001). Conclusion: Pre operative higher ASA grade independently predicted post operative acute kidney injury. Post operative AKI is significantly associated with mortality.

scholarly journals Incidence And Outcome of Acute Kidney Injury in Critically ill Children at Dr. Soetomo Hospital Surabaya

2015 ◽  
Vol 38 (3) ◽  
pp. 120-123 ◽  
Author(s):  
Risky Vitria Prasetyo ◽  
Putu Dian Saraswati ◽  
Idaa Shinta Kamaya ◽  
Septria Erlitarini Sudjito ◽  
Muhammad Riza Kurniawan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Demographic Data ◽  
Kidney Injury ◽  
Pediatric Intensive Care ◽  
Critically Ill Children ◽  
Chi Square ◽  
Female Ratio ◽  
Chi Square Test ◽  
End Stage

Background: The development of acute kidney injury (AKI) in critically ill patients, or AKI children worsened to be critically ill, is associated with increased morbidity and mortality. Early detection on AKI improves its poor outcome in those children. To study the incidence and correlate the outcome of critically ill children with AKI in children admitted to Pediatric Intensive Care Unit (PICU) at Dr. Soetomo Hospital Surabaya. Methodology: We prospectively studied children admitted to PICU during 15 January to 14 April 2014. Demographic data including age and sex, PICU indications, and AKI staging were recorded. All data were analyzed by descriptive statistics and chi-square test (P<0.05). Results: A total of 119 children were admitted to PICU during study period. Among those, 63 children were excluded for being <3 months old, had end-stage kidney disease or complex cardiac problem, and children underwent cardiac catheterization. The remaining 56 (47.1%) were studied further, mean age was 49.7 (SD 46.2) months, male-to-female ratio was 1.2:1. Indication for PICU admission was dominated by shock (35.7%), followed by central nervous system (CNS) dysfunction in 13 (23.2%) and respiratory failure in 12 (21.4%) children. AKI was noted in 15 (26.8%) children, mostly (10.7%) in Injury stage with 5 (8.9%) in Risk and 4 (7.1%) in Failure stages. Twelve (21.4%) children died, 7 (58.3%) had AKI with 3 (25.0%) each in Risk and Failure stages while 1 (8.3%) in Injury (P<0.05). Conclusion: The incidence of AKI was moderate in critically ill children but significantly associated with mortality rate. DOI: http://dx.doi.org/10.3329/bjch.v38i3.22818 Bangladesh J Child Health 2014; VOL 38 (3) :120-123

scholarly journals The beneficial effects of plasma exchange for treatment of acute kidney injury in minimal change nephrotic syndrome

2011 ◽  
Vol 45 (2) ◽  
pp. 179-185
Author(s):  
Hideyo Oguchi ◽  
Marohito Murakami ◽  
Takashi Araki ◽  
Mariko Meguro ◽  
Akinori Hashiguchi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Nephrotic Syndrome ◽  
Plasma Exchange ◽  
Kidney Injury ◽  
Minimal Change Nephrotic Syndrome ◽  
Minimal Change ◽  
Beneficial Effects

scholarly journals P0517RENAL STEM CELLS (ARPCS) AS A NEPHROPROTECTIVE APPROACH DURING CISPLATIN-INDUCED ACUTE KIDNEY INJURY: A DEFENSE MECHANISM BY EXTRACELLULAR VESICLES CARRYING THE CYP1B1 GENE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
ROSSANA FRANZIN ◽  
Fabio Sallustio ◽  
Claudia Curci ◽  
Simona Simone ◽  
Angela Picerno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Extracellular Vesicles ◽  
Caspase 3 ◽  
Defense Mechanism ◽  
Kidney Injury ◽  
The Body ◽  
Cell Culture Supernatant ◽  
Protective Agent ◽  
Cyp1b1 Gene

Abstract Background and Aims Cisplatin, is a nonspecific cytotoxic agent that primarily interferes with cellular DNA replication and the cell cycle, nevertheless it lacks tumor selectivity and acts also in normal cells. The most serious adverse reaction of cisplatin is Acute Kidney Injury (AKI), limiting its use and efficacy in chemotherapy. Cisplatin nephrotoxicity is observed in more than 30% of older patients, however the mechanism of nephrotoxicity remains unclear and specific preventive measures are not available. Today, there is an urgent need for specific nephroprotective strategies to be used during cisplatin chemotherapy. Recently, we found that tubular stem/progenitor cells (tARPC) are able to protect the tubular epithelial (RPTEC) from cisplatin induced injury, preserving their proliferation and inhibiting apoptosis. The aim of this study was to identify the molecular mechanisms involved in tARPC-mediated resistance to cisplatin. Method Co-cultures of RPTEC cells and tARPCs were exposed to cisplatin (2.5 µM) for 6 h and then kept in culture for 96 h. Gene expression profile was obtained from tARPCs and RPTECs by Agilent SurePrint G3 Human Gene Expression Microarrays. Genespring and R software were used for the analysis. Gene expression data were validated by Real-time PCR. Extracellular vesicles were isolated from cell culture supernatant by miRCURY Exosome Cell/Urine/CSF Kit (Qiagen) and RNA contained in extracellular vesicles was purified, analyzed in quality by Bioanalyzer (RNA nano) and evaluated by qPCR. The BrdU assay and caspase 3 were used to measure proliferation and apoptosis levels. Immunohistochemical expression of activated caspase-3 was used as a marker of apoptosis in RPTECs. Results By a whole-genome gene expression analysis, we found 107 genes specifically modulated by RPTECs in response to cisplatin and, among these, 30 genes induced by ARPCs following the cisplatin damage. In particular, we found a strong upregulation of the CYP1B1 gene (false discovery rate corrected p value &lt;0.05; fold change=4,1). The qPCR confirmed the increase in CYP1B1 levels in the co-cultures with respect to the respective basal conditions (p &lt;0.05). Interestingly, the CYP1B1 mRNA was also enveloped in Extracellular Vesicles released in the cell co-culture media by tARPC and RPTEC after cisplatin exposition. The CYP1B1 gene encodes a member of the cytochrome P450 superfamily of enzymes and the produced enzyme metabolizes procarcinogens, such as polycyclic aromatic hydrocarbons. CYP1B1 has been shown to be active within tumors and is also capable of metabolizing a structurally diverse range of anticancer drugs. It is responsible for the resistance to docetaxel, cisplatin, tamoxifen and nucleoside analogues. CYP1B1 is involved in the detoxification of the body by various exogenous toxic agents, including cisplatin. We found that CYP1B1 gene was expressed at low levels in RPTECs and in cisplatin-damaged RPTECs. Moreover, 96 h days after 2.5 μM exposure to cisplatin, RPTECs reduced the proliferation and underwent in apoptosis, as showed by caspase 3. However, in co-culture with ARPCs, ARPC cellular and extracellular vesicles CYP1B1 gene expression significantly increased, the apoptotic process was stopped and RPTECs increased their proliferation rate. These data support the hypothesis that ARPCs are sensor of cisplatin damaged-RPTEC and confers cisplatin resistance by transferring CYP1B1 gene in extracellular vesicles. Conclusion This is the first evidence of a cisplatin-induced overexpression of CYP1b1 in renal epithelial cells as a defense mechanism against cisplatin toxicity. This is consistent with our previous data showing that renal progenitors are resistant to cisplatin. The findings may have biological and clinical significance in terms of their implications in cellular communications and potential use of CYP1B1 as biomarkers for AKI induced by cisplatin or as protective agent.

scholarly journals The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Junjie Hang ◽  
Steven Yuk-Fai Lau ◽  
Ruohan Yin ◽  
Lina Zhu ◽  
Siyuan Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Value ◽  
Chi Square ◽  
Catalytic Subunits ◽  
Beneficial Effects ◽  
Phosphoprotein Phosphatases ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Independent Cohort

Abstract Compelling evidence suggests that phosphoprotein phosphatases (PPPs) are involved in a large spectrum of physiological and pathological processes, but little is known about their roles in pancreatic cancer. We investigated the expression level, prognostic value, and potential function of PPPs with data from Oncomine, GEPIA, THPA, and TCGA databases and an independent cohort of patients with pancreatic cancer. Among all the PPP catalytic subunits (PPPcs), the transcription levels of PPP1CA, PPP1CB, PPP3CA, PPP3CB, and PPP4C were higher in pancreatic cancer than in normal pancreas (P&lt;0.01, fold change &gt; 2). Kaplan–Meier analysis showed that high transcription levels of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, and PPP4C correlated with poorer survival. In contrast, patients with high levels of PPP3CB, PPP3CC, PPP5C, PPP6C, and PPEF2 had much better prognoses. Data from THPA and patients with pancreatic cancer enrolled in our hospital also confirmed the prognostic value of PPP1CA, PPP1CB, PPP2CA, PPP2CB, PPP3CA, PPP3CB, and PPP6C at the protein level. In addition, the Pearson Chi-square test showed that PPP3CB level was significantly correlated with T and N stages. GO and KEGG analyses showed that the genes and pathways related to the pathogenesis and progression of pancreatic cancer were greatly affected by alterations in PPPcs. Results of the present study suggest that PPP1CA, PPP1CB, PPP2CA, PPP2CB, and PPP3CA have deleterious effects but PPP3CB, PPP5C, and PPP6C have beneficial effects on pancreatic cancer.

scholarly journals Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yun Tang ◽  
Xiaobo Yang ◽  
Huaqing Shu ◽  
Yuan Yu ◽  
Shangwen Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Blood Samples ◽  
Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

scholarly journals Acute Kidney Injury in Patients With Acute Chemical Poisoning: the Experience of the Toxicological Center in Ryazan

2021 ◽  
Vol 9 (4) ◽  
pp. 639-645
Author(s):  
N. V. Shatrova ◽  
M. N. Rudakova ◽  
L. G. Zaytseva ◽  
Zh. A. Varenova
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Acute Poisoning ◽  
Annual Reports ◽  
Infusion Therapy ◽  
Chi Square ◽  
Exact Test ◽  
Risk Of Death ◽  
Increased Risk ◽  
Microsoft Office

Relevance. Acute kidney injury (AKI) is one of the leading causes of death worldwide. However, the epidemiology of AKI is not well understood. In Russia, toxic kidney damage plays a significant role in the nosological structure of AKI — 12.2%.Aim of study. To study the features of AKI in patients with acute chemical poisoning.Material and methods. We analyzed 26 case histories of patients with acute chemical poisoning with AKI (according to KDIGO). The comparison group included 25 patients with acute chemical poisoning without AKI. All patients were hospitalized in a toxicological center on the basis of the emergency department of the Ryazan Region State Budgetary Institution “City Clinical Emergency Hospital” (SBI RR “CCH EMC”) in 2016–2018. The analysis of the annual reports of the chief toxicologist of the Ministry of Health of the Ryazan Region for 2016–2018 was carried out. Data processing was performed using Microsoft Office Excel 2013 and on the website medstatistic.ru (Pearson’s chi-square test and Fisher’s exact test).Results. In most patients AKI developed during poisoning with cauterizing action substances - 38.4% (23% - vinegar essence, 15.4% - unidentified cauterizing action substance). The poisoning with alcohol substitutes (12%) took the 2nd place, with narcotic substances (8%) – the 3 rd place. Also, isolated cases of AKI (4% each) were reported in case of poisoning with pregabalin, tramadol, ketorol and ethanol. Poisoning with an unknown toxicant was noted in 29.6% of cases. Most patients (69.2%.) had stage 3 AKI. The second stage was registered in 7.7% of patients, the first — in 23.1%. Proteinuria was detected in all patients who underwent common urine test (CUT). Infusion therapy using crystalloids was performed in 100% of cases.Conclusion. Acute renal injury most often develops in acute poisoning with cauterizing poisons. The development of acute kidney injury in acute chemical poisoning leads to an increased risk of death. Acute kidney injury is the second most common immediate cause of death in acute chemical poisoning. Infusion therapy is an integral part of the management of toxicological patients with acute kidney injury.

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