Dataset Information

SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.

ABSTRACT: Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.

SUBMITTER: Xu S

PROVIDER: S-EPMC5149703 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.

Xu Siqi S Gao Youguang Y Zhang Qin Q Wei Siwei S Chen Zhongqing Z Dai Xingui X Zeng Zhenhua Z Zhao Ke-Seng KS

Oxidative medicine and cellular longevity 20161128

Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue ...[more]

PMID: 28003866

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Project description:The relationship between cardiac output and septic acute kidney injury (AKI) remains unclear. The purpose of this study was to assess the association between the cardiac index (CI) and the renal outcomes in patients with septic shock.A one-year prospective cohort study was performed in the surgical and medical ICU of a teaching hospital in Nanjing, China. Twenty-nine septic shock patients who required early goal-directed fluid resuscitation were consecutively included. Pulse indicator continuous cardiac output (PiCCO) device was used to measure hemodynamic parameters before and after early goal-directed therapy (EGDT). Based on CI changes after EGDT, patients were assign to the CI increased group or the CI constant group, respectively. The incidence of poor renal outcome, which was defined as AKI on admission without recovery in following three days or new onset AKI within 28 days, was recorded. We investigated whether an increased CI was associated with a better renal outcome.After EGDT, there were 16 patients in the CI increased group and 13 patients in the CI constant group. The incidence of poor renal outcome was lower in CI increased group than in the CI constant group (6% vs. 62%; P?=?0.003) with a relative risk of 0.10. The logistic regression showed that the CI percent change was associated with renal outcome, with an odd ratio of 0.003 (P?=?0.056) after adjustment of possible confounding factors. The CI percent change would predict a good renal outcome (AU ROC 0.739, P?=?0.012) with moderate accuracy (sensitivity 75% and specificity 89%) when using a 10% cut-off value from Youden index. The CI percent change was also positively correlated with creatinine clearance (CCr) after EGDT (??=?0.548; P?=?0.002).The increased CI after EGDT was a protective factor for kidney in patients with septic shock. A CI increased above 10% could be potentially used to predict development and reversibility of AKI in septic shock patients.Clinicaltrials.gov:NCT01862588 (May 13, 2013).

Project description:ObjectiveThe development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock.DesignCandidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects.SettingMultiple PICUs in the United States.InterventionsNone other than standard care.Measurements and main resultsThe decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk.ConclusionsWe have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation.

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SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.

Publications

SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model.

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