Sepsis-associated acute kidney injury – is it possible to move the needle against this syndrome?

Devarajan, Prasad; Basu, Rajit K.

doi:10.1016/j.jped.2016.09.001

Cited by 7 publications

(6 citation statements)

References 26 publications

(30 reference statements)

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“…AKI is one of the common complications of sepsis, mainly manifested as renal tubular injury [ 31 ]. Heretofore, there is no effective treatment for septic AKI.…”

Section: Discussionmentioning

confidence: 99%

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells

Feng

Zhao

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown. Methods. The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway. Results. An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells. Conclusion. All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.

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“…AKI is one of the common complications of sepsis, mainly manifested as renal tubular injury [ 31 ]. Heretofore, there is no effective treatment for septic AKI.…”

Section: Discussionmentioning

confidence: 99%

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells

Feng

Zhao

Liu

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Acute kidney injury (AKI) is one of the most common and the most serious complications of sepsis. Septic AKI accounts for 33-50% of all AKI in adults and 25-50% of those in children [3]. Patients with septic AKI have a higher burden of illness, greater abnormalities in acute physiology, and greater nonrenal organ failure when compared with nonseptic AKI [4].…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective Effect of Heat Shock Protein 27 Against Lipopolysaccharide-Induced Apoptosis of Renal Epithelial HK-2 Cells

Li¹,

Li³

et al. 2017

Cell Physiol Biochem

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Background:In response to various stimuli, heat shock protein 27 (Hsp27) functions as an anti-apoptotic or/and anti-inflammatory factor which confers a survival advantage to cells. This study was aimed to explore whether Hsp27 also has a cytoprotective role in human renal tubular epithelial cells, and to evaluate its potential in treating septic acute kidney injury (septic AKI). Methods: HK-2 cells were subjected to different concentrations (0-10 μg/mL) of lipopolysaccharide (LPS) for various times (0-24 h) to establish a septic AKI model in vitro. Before LPS administration, HK-2 cells were transfected either with vectors or siRNA against Hsp27, and the changes in cell viability and apoptotic cells rate were assessed using CCK-8 and flow cytometry. The expression changes in apoptosis-related proteins, proinflammatory cytokines and chemokine, as well as main factors in NF-κB and JNK pathways were mainly determined by Western blotting. Besides, the relationship between Hsp27 and Bcl-2 was detected by co-immunoprecipitation. Results: LPS remarkably damaged HK-2 cells by reduction of cell viability, induction of apoptosis, and stimulation of proinflammatory cytokines and chemokine release. Hsp27 overexpression significantly impaired LPS-induced damage in HK-2 cells. Hsp27 overexpression couldn't alter the mRNA level of Bcl-2, but could interact with Bcl-2 at an endogenous level. Both NF-κB and JNK pathways were activated by LPS, while were blocked in Hsp27-overexpressing cells. Conclusion: Hsp27 overexpression conferred a survival advantage to LPS-injured HK-2 cells by controlling cell viability, apoptosis and inflammation, possibly via interaction with Bcl-2 and modulation of NF-κB and JNK pathways.

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“…When comparing the data collected in the ICUad, there was no difference between the groups for serum creatinine (survivors: 1.1 [0.7-1.7] mg/dL vs. nonsurvivors: 1.1 [0.8-1.6] mg/dL; p-value 0.547), but oliguria upon admission was more frequent among non-survivors (n= 25; 10.3% vs. survivors group: n= 11; 3.0%; p-value <0.001). Similarly, APACHE II score was also significantly higher among those who died (median 28 [23][24][25][26][27][28][29][30][31] Non-survivors had less need for NSAIDs (n= 98, 40.3% vs. survivor group: n= 216, 58.4%, p-value <0.001), but higher fluid balance alterations and higher frequency of organ dysfunction ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…[18][19][20][21][22] Considering that septic patients can benefit from volume expansion in the early hours, it is emphasized that volume replacement should occur until the intravascular volume is restored, with minimum fluid administration. 22 Sepsis is the main AKI cause, 5 substantially increases the risk of death in the critically ill patients, both in adult and pediatric populations, 23 and contributes to the progression of chronic kidney disease after AKI. 24 We did not include sepsis occurrence and sepsis-associated AKI in the multivariate models of mortality due to multicollinearity.…”

Section: Discussionmentioning

confidence: 99%

Non-recovery of renal function is a strong independent risk factor associated with mortality in AKI patients

et al. 2020

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Introduction: Acute kidney injury (AKI) is a recurrent complication in the intensive care unit (ICU) and is associated with negative outcomes. Objective: To investigate factors associated with mortality in critically ill AKI patients in a South Brazilian ICU. Methods: The study was observational retrospective involving AKI patients admitted to the ICU between January 2011 and December 2016 of at least 18 years old upon admission and who remained in the ICU at least 48 hours. Comparisons between selected characteristics of survivor and non-survivor groups were done using univariate analysis; multivariate logistic regression was applied to determine factors associated with patient mortality. Results: Of 838 eligible patients, 613 participated in the study. Men represented the majority (61.2%) of the patients, the median age was 53 years, and the global mortality rate was 39.6% (n= 243). Non-recovery of renal function after AKI (OR= 92.7 [38.43 - 223.62]; p <0.001), major surgery-associated AKI diagnosis (OR= 16.22 [3.49 - 75.38]; p <0.001), and the use of vasoactive drugs during the ICU stay (OR = 11.49 [2.46 - 53.70]; p <0.002) were the main factors independently associated with patient mortality. Conclusion: The mortality rate observed in this study was similar to that verified in other centers. Non-recovery of renal function was the variable most strongly associated with patient mortality, suggesting that the prevention of factors that aggravate or maintain the AKI episode should be actively identified and mitigated, possibly constituting an important strategy to reduce mortality in AKI patients.

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Sepsis-associated acute kidney injury – is it possible to move the needle against this syndrome?

Cited by 7 publications

References 26 publications

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells

Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells

Cytoprotective Effect of Heat Shock Protein 27 Against Lipopolysaccharide-Induced Apoptosis of Renal Epithelial HK-2 Cells

Non-recovery of renal function is a strong independent risk factor associated with mortality in AKI patients

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