Cellular and Molecular Mechanisms of AKI

Agarwal, Anupam; Dong, Zheng; Harris, Raymond C.; Murray, Patrick; Parikh, Samir M.; Rosner, Mitchell H.; Kellum, John A.; Ronco, Claudio

doi:10.1681/asn.2015070740

Cited by 167 publications

(158 citation statements)

References 115 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…These risk factors have been poorly considered in setting animal models for AKI. The Acute Dialysis Quality Initiative XIII Working Group proposed the development of context-specific preclinical models that not only replicate the exposures but also consider the human complexity [2]. Interesting findings from single experimental models should be validated in more realistic models and then tested in human AKI.…”

Section: Disconnection Between Preclinical and Clinical Aki Studies: mentioning

confidence: 99%

“…By contrast, most preclinical studies mainly focused on a prophylactic approach, where the protective agents are administered before the renal insult (primary prevention) [7]. In this setting, a secondary prevention approach, where a potential treatment is given when AKI is already established, might be more realistic, and closer to the human condition [2]. …”

Section: Disconnection Between Preclinical and Clinical Aki Studies: mentioning

confidence: 99%

“…1). In this scenario, since human AKI is hard to prevent in clinical practice, it is also important that future preclinical studies should prioritize secondary prevention, where candidate interventions are administered when AKI is already present, at least by biomarkers, instead of using them prophylactically [2]. In order to achieve these goals, given the high heterogeneity of AKI, there is a critical need to establish collaborations among centers and develop networks and databanks to collect clinical and biological information on AKI patients characterized by specific history of disease, clinical course, and, where possible, histopathology [4].…”

Section: Future Directionsmentioning

confidence: 99%

“…In order to achieve these goals, given the high heterogeneity of AKI, there is a critical need to establish collaborations among centers and develop networks and databanks to collect clinical and biological information on AKI patients characterized by specific history of disease, clinical course, and, where possible, histopathology [4]. Importantly, a strong relationship between academia and industry is urgently recommended for improving the design of both preclinical and clinical studies [2]. The use of standardized definitions of AKI among preclinical and clinical studies and the inclusion of AKI biomarkers both for patient selection, and even possibly as endpoints, is crucial to predict and monitor the response to novel AKI therapies [3].…”

Section: Future Directionsmentioning

confidence: 99%

“…Several advances have been made in the early recognition of clinical AKI and its risk factors. Similarly, several cellular and molecular mechanisms and potential targets of AKI have been investigated in recent years in various preclinical models [2]. However, these promising findings were not successfully confirmed in clinical studies and no effective AKI therapies have been approved to date.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury

Fiorentino

Kellum

2018

Nephron

View full text Add to dashboard Cite

Background: Several cellular and molecular targets and mechanisms have been investigated in preclinical studies of acute kidney injury (AKI), but translation in successful clinical studies has failed to date. This article reviews many issues that have limited this and the potential future perspectives in AKI prevention and treatment. Summary: Preclinical models of AKI should closely mimic the complexity of human AKI, considering the importance of several comorbidities in determining the clinical course and outcomes in the human disease. Moreover, studies should test novel interventions in models where AKI is already established, instead of focusing only at primary prevention. AKI definitions and endpoints in animal studies should be similar to those applied in clinical studies; in particular, AKI biomarkers should be implemented to guide patient selection for clinical trials and monitor intervention efficacy. In this scenario, cell-cycle arrest biomarkers have been widely investigated as AKI predictors in both preclinical and clinical studies and they serve as useful tools for future interventional studies. A better understanding of human AKI through a large collection of biological samples and kidney biopsies and omics applications, and an iterative relationship between preclinical and clinical studies are critical steps to improve future preclinical models and clinical trials. Finally, given the great variability in clinical manifestation of AKI, a strong collaboration between research centers and industry is recommended. Key messages: Several methodological issues have hampered the translation of basic research findings in clinical studies, and overcoming these obstacles is necessary to achieve success.

show abstract

Section: Disconnection Between Preclinical and Clinical Aki Studies: mentioning

confidence: 99%

Section: Disconnection Between Preclinical and Clinical Aki Studies: mentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury

Fiorentino

Kellum

2018

Nephron

View full text Add to dashboard Cite

show abstract

Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL‐33/ST2 to Alleviate Renal Ischemia‐Reperfusion Injury

Xu,

Xing,

Yuan

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

Renal ischemia‐reperfusion injury (IRI) is a common disease with high morbidity and mortality. Renal IRI can cause the disorder of immune microenvironment and reprograming the immune microenvironment to alleviate excessive inflammatory response is crucial for its treatment. Cytokine IL‐33 can improve the immune inflammatory microenvironment by modulating both innate and adaptive immune cells, and serve as an important target for modulating immune microenvironment of renal IRI. Herein, we report that bilobetin‐functionalized ultra‐small Cu2‐xSe nanoparticles (i.e., CSPB NPs) can activate the PKA/p‐CREB/IL‐33/ST2 signaling pathway to regulate innate and adaptive immune cells for reprograming the immune microenvironment of IRI‐induced acute kidney injury (AKI). The biocompatible CSPB NPs can promote the polarization of M1‐like macrophages into M2‐like macrophages, and the expansion of ILC2 and Treg cells by activating IL‐33/ST2 to modulate the excessive immune inflammatory response of renal IRI. More importantly, they can rapidly accumulate at the injured kidney to significantly alleviate IRI. This work demonstrates that modulating the expression of cytokines to reprogram immune microenvironment has great potential in the treatment of renal IRI and other ischemic diseases.This article is protected by copyright. All rights reserved

show abstract

Redox‐Mediated Artificial Non‐Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation

Zhao

Wang

et al. 2021

Advanced Science

View full text Add to dashboard Cite

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti 3 C 2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti 3 C 2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-B signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.

show abstract

Cellular and Molecular Mechanisms of AKI

Cited by 167 publications

References 115 publications

Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury

Improving Translation from Preclinical Studies to Clinical Trials in Acute Kidney Injury

Ultrasmall Nanoparticles Regulate Immune Microenvironment by Activating IL‐33/ST2 to Alleviate Renal Ischemia‐Reperfusion Injury

Redox‐Mediated Artificial Non‐Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation

Contact Info

Product

Resources

About