Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury

Background: Acute kidney injury (AKI) is a common disease that can develop into end-stage kidney disease. Sepsis is one of the main causes of AKI. Currently, there is no satisfactory way to treat septic AKI. Therefore, we have shown the protective function of Cul4a in septic AKI and its molecular mechanism. Methods: The cellular and animal models of septic AKI were established by using lipopolysaccharide (LPS). Western blot (WB) was employed to analyze Cul4a expression. RT-qPCR was employed to test the expression of Cul4a, SOD1, SOD2, GPX1, CAT, IL-6, TNF-α, Bcl-2, IL-1β, Bax and KIM-1 mRNA. ELISA was performed to detect the contents of inflammatory factors and LDH. CCK-8 was utilized to detect the cell viability. Flow cytometry was utilized to analyze the apoptosis. DHE-ROS kit was used to detect the content of ROS. Results: Cul4a was down-regulated in cellular and animal models of septic AKI. Oxidative stress is obviously induced by LPS, as well as apoptosis and inflammation. However, these can be significantly inhibited by up-regulating Cul4a. Moreover, LPS induced the activation of the NF-κB pathway, which could also be inhibited by overexpression of Cul4a. Conclusion: Cul4a was found to be a protective factor in septic AKI, which could inhibit LPS-induced oxidative stress, apoptosis and inflammation of HK-2 cells by inhibiting NF-κB pathway.

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Large animal models for translational research in acute kidney injury

Renal Failure ◽

10.1080/0886022x.2020.1830108 ◽

2020 ◽

Vol 42 (1) ◽

pp. 1042-1058

Author(s):

Balamurugan Packialakshmi ◽

Ian J. Stewart ◽

David M. Burmeister ◽

Kevin K. Chung ◽

Xiaoming Zhou

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Translational Research ◽

Kidney Injury ◽

Large Animal ◽

Large Animal Models

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MP240DEVELOPMENT OF AN “IN SITU” RENAL PERFUSION SYSTEM TO STUDY THE ORIGIN OF URINARY BIOMARKERS IN TWO ANIMAL MODELS OF ACUTE KIDNEY INJURY INDUCED BY GENTAMICIN AND ISCHEMIA-REPERFUSION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx166.mp240 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii514-iii514

Author(s):

Víctor Blanco-Gozalo ◽

Laura Prieto-García ◽

Sandra Sancho-Martínez ◽

Yaremi Quiros-Luis ◽

José López-Novoa ◽

...

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Perfusion ◽

Urinary Biomarkers ◽

Perfusion System

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Found in Translation: Reasons for Optimism in the Pursuit to Prevent Chronic Kidney Disease After Acute Kidney Injury

Canadian Journal of Kidney Health and Disease ◽

10.1177/2054358119868740 ◽

2019 ◽

Vol 6 ◽

pp. 205435811986874

Author(s):

Samuel A. Silver ◽

Casimiro Gerarduzzi

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Animal Models ◽

Kidney Injury ◽

Narrative Review ◽

Sources Of Information ◽

Stage Renal Disease ◽

End Stage ◽

Injury Progression

Purpose of review: The current review will discuss on the progress of studying the transition phase between acute kidney injury (AKI) and chronic kidney disease (CKD) through improved animal models, common AKI and CKD pathways, and how human studies may inform different translational approaches. Sources of information: PubMed and Google Scholar. Methods: A narrative review was performed using the main terms “acute kidney injury,” “chronic kidney disease,” “end-stage renal disease,” “animal models,” “review,” “decision-making,” and “translational research.” Key findings: The last decade has shown much progress in the study of AKI, including evidence of a pathophysiological link between AKI and CKD. We are now in a phase of redesigning animal models and discovering mechanisms that can replicate the pathological conditions of the AKI-to-CKD continuum. Translating these findings into the clinic is a barrier that must be overcome. To this end, current efforts include prediction of AKI onset and maladaptive repair, detecting patients susceptible to the progression of chronic maladaptive repair, and understanding shared signaling mechanisms between AKI and CKD. Limitations: This is a narrative review of the literature that is partially influenced by the knowledge, perspectives, and experiences of the authors and their research background. Implications: Overall, this new knowledge from the AKI-to-CKD continuum will help bridge the discontinuity that exists between animal models and patients, resulting in more effective translational biomarkers and therapeutics to test in known AKI pathologies thereby preventing the chronicity of kidney injury progression.

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Megalin in acute kidney injury: foe and friend

AJP Renal Physiology ◽

10.1152/ajprenal.00378.2013 ◽

2014 ◽

Vol 306 (2) ◽

pp. F147-F154 ◽

Cited By ~ 20

Author(s):

Ravikiran Mahadevappa ◽

Rikke Nielsen ◽

Erik Ilsø Christensen ◽

Henrik Birn

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Proximal Tubule ◽

Essential Role ◽

Kidney Injury ◽

Current Evidence ◽

Renal Protection ◽

Tubule Cell ◽

Cellular Protection ◽

And Function

The kidney proximal tubule is a key target in many forms of acute kidney injury (AKI). The multiligand receptor megalin is responsible for the normal proximal tubule uptake of filtered molecules, including nephrotoxins, cytokines, and markers of AKI. By mediating the uptake of nephrotoxins, megalin plays an essential role in the development of some types of AKI. However, megalin also mediates the tubular uptake of molecules implicated in the protection against AKI, and changes in megalin expression have been demonstrated in AKI in animal models. Thus, modulation of megalin expression in response to AKI may be an important part of the tubule cell adaption to cellular protection and regeneration and should be further investigated as a potential target of intervention. This review explores current evidence linking megalin expression and function to the development, diagnosis, and progression of AKI as well as renal protection against AKI.

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Catalytic iron and acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00388.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. F871-F876 ◽

Cited By ~ 18

Author(s):

David E. Leaf ◽

Dorine W. Swinkels

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Length Of Stay ◽

Kidney Injury ◽

Redox Cycling ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Translational Studies ◽

Labile Iron

Acute kidney injury (AKI) is a common and often devastating condition among hospitalized patients and is associated with markedly increased hospital length of stay, mortality, and cost. The pathogenesis of AKI is complex, but animal models support an important role for catalytic iron in causing AKI. Catalytic iron, also known as labile iron, is a transitional pool of non-transferrin-bound iron that is readily available to participate in redox cycling. Initial findings related to catalytic iron and animal models of kidney injury have only recently been extended to human AKI. In this review, we discuss the role of catalytic iron in human AKI, focusing on recent translational studies in humans, assay considerations, and potential therapeutic targets for future interventional studies.

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The Kynurenine Pathway in Acute Kidney Injury and Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000519811 ◽

2021 ◽

pp. 1-17

Author(s):

Hai Ning Wee ◽

Jian-Jun Liu ◽

Jianhong Ching ◽

Jean-Paul Kovalik ◽

Su Chi Lim

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Animal Models ◽

Kidney Diseases ◽

Kidney Injury ◽

Kynurenine Pathway ◽

T Cell Subsets ◽

Renal Diseases ◽

Tryptophan Degradation

Background: The kynurenine pathway (KP) is the major catabolic pathway for tryptophan degradation. The KP plays an important role as the sole de novo nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway in normal human physiology and functions as a counter-regulatory mechanism to mitigate immune responses during inflammation. Although the KP has been implicated in a variety of disorders including Huntington’s disease, seizures, cardiovascular disease, and osteoporosis, its role in renal diseases is seldom discussed. Summary: This review summarizes the roles of the KP and its metabolites in acute kidney injury (AKI) and chronic kidney disease (CKD) based on current literature evidence. Metabolomics studies demonstrated that the KP metabolites were significantly altered in patients and animal models with AKI or CKD. The diagnostic and prognostic values of the KP metabolites in AKI and CKD were highlighted in cross-sectional and longitudinal human observational studies. The biological impact of the KP on the pathophysiology of AKI and CKD has been studied in experimental models of different etiologies. In particular, the activation of the KP was found to confer protection in animal models of glomerulonephritis, and its immunomodulatory mechanism may involve the regulation of T cell subsets such as Th17 and regulatory T cells. Manipulation of the KP to increase NAD+ production or diversion toward specific KP metabolites was also found to be beneficial in animal models of AKI. Key Messages: KP metabolites are reported to be dysregulated in human observational and animal experimental studies of AKI and CKD. In AKI, the magnitude and direction of changes in the KP depend on the etiology of the damage. In CKD, KP metabolites are altered with the onset and progression of CKD all the way to advanced stages of the disease, including uremia and its related vascular complications. The activation of the KP and diversion to specific sub-branches are currently being explored as therapeutic strategies in these diseases, especially with regards to the immunomodulatory effects of certain KP metabolites. Further elucidation of the KP may hold promise for the development of biomarkers and targeted therapies for these kidney diseases.

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Aging Male Spontaneously Hypertensive Rat as an Animal Model for the Evaluation of the Interplay between Contrast-Induced Acute Kidney Injury and Cardiorenal Syndrome in Humans

Cardiorenal Medicine ◽

10.1159/000447542 ◽

2016 ◽

Vol 7 (1) ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Jun Zhang ◽

Mohammad Kazem Fallahzadeh ◽

Peter A. McCullough

Keyword(s):

Acute Kidney Injury ◽

Animal Models ◽

Spontaneously Hypertensive Rat ◽

Kidney Injury ◽

Cardiorenal Syndrome ◽

Suitable Model ◽

Aging Male ◽

Spontaneously Hypertensive ◽

Hypertensive Rat

Background: Although there are some animal models for biomarkers of contrast-induced acute kidney injury (CI-AKI), for cardiorenal syndrome (CRS) and for acute renal failure, the interplay between CI-AKI and CRS has yet to be evaluated. Insight into the pathogenesis of CRS is urgently needed from animal models in order to foster the discovery and implementation of novel biomarkers for this disease. Specially designed animal models for type 1 and 3 CRS, particularly CI-AKI, have not yet emerged. Summary: We hypothesize that the aging male spontaneously hypertensive rat (SHR) is likely to be a suitable model. The SHR model is able to mimic risk factors for preclinical CRS that appears in the clinical setting, specifically hypertension, age, preexisting damage and dysfunction of the heart and kidney, endothelial dysfunction, increased level of reactive oxygen species, decreased level and bioavailability of nitric oxide (NO), impairment of the L-arginine-NO pathway, and insulin resistance. In the SHR, CI-AKI results in a different profile of AKI biomarkers than is seen with preexisting chronic kidney injury. Key Messages: The SHR model can be used to evaluate the interaction between CI-AKI and CRS type 1 and 3 and to verify neutrophil gelatinase-associated lipocalin (NGAL) as a reliable CI-AKI biomarker for clinical application. Further research is warranted with a large number of aging male SHRs to prove NGAL as a sensitive, specific, highly predictive, early biomarker for CI-AKI.

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