AKI and Genetics: Evolving Concepts in the Genetics of Acute Kidney Injury: Implications for Pediatric AKI

Lee-Son, Kathy

doi:10.1055/s-0035-1557112

Cited by 3 publications

(1 citation statement)

References 79 publications

(79 reference statements)

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“…16,17 It is becoming increasingly apparent that genetic heterogeneity within patient cohorts adds another element of complexity that may affect the response to promising therapies, and research initiatives in this area on relevant patient populations will hopefully inform the design of better preclinical models. 18-21 In contrast, preclinical studies are typically performed on pure disease processes with minimal consideration given to the genetic background of the model or cell line chosen. 22 The context of treatment must also be considered—many preclinical studies attempt to prevent renal injury in response to a specific insult, whereas, in clinical practice, AKI is usually established at the time therapy is being considered.…”

Section: Challenges Of Preclinical Studiesmentioning

confidence: 99%

Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review

Misra

Silva²,

Collister

2019

Can J Kidney Health Dis

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Background: Acute kidney injury (AKI) is a complex and heterogeneous clinical syndrome with limited effective treatment options. Therefore, a coherent research structure considering AKI pathophysiology, treatment, translation, and implementation is critical to advancing patient care in this area. Purpose of review: In this narrative review, we discuss novel therapies for AKI from their journey from bench to bedside to population and focus on roadblocks and opportunities to their successful implementation. Sources of information: Peer-reviewed articles, opinion pieces from research leaders and research funding agencies, and clinical and research expertise. Methods: This narrative review details the challenges of translation of preclinical studies in AKI and highlights trending research areas and innovative designs in the field. Key developments in preclinical research, clinical trials, and knowledge translation are discussed. Furthermore, this article discusses the current need to involve patients in clinical research and the barriers and opportunities for effective knowledge translation. Key findings: Preclinical studies have largely been unsuccessful in generating novel therapies for AKI, due both to the complexity and heterogeneity of the disease, as well as the limitations of commonly available preclinical models of AKI. The emergence of kidney organoid technology may be an opportunity to reverse this trend. However, the roadblocks encountered at the bench have not precluded researchers from running well-designed and impactful clinical trials, and the field of renal replacement therapy in AKI is highlighted as an area that has been particularly active. Meanwhile, knowledge translation initiatives are bolstered by the presence of large administrative databases to permit ongoing monitoring of clinical practices and outcomes, with research output from such evaluations having the potential to directly impact patient care and inform the generation of meaningful clinical practice guidelines. Limitations: There are limited objective data examining the process of knowledge creation and translation in AKI, and as such the opinions and research areas of the authors are significantly drawn upon in the discussion. Implications: The use of an organized knowledge-to-action framework involving multiple stakeholders, especially patient partners, is critical to translating basic research findings to improvements in patient care in AKI, an area where effective treatment options are lacking.

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Section: Challenges Of Preclinical Studiesmentioning

confidence: 99%

Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review

Misra

Silva²,

Collister

2019

Can J Kidney Health Dis

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Ecological aspects of molecular mechanisms of epigenetic rearrangement of humoral systems of the renal function regulation

Dolomatov

Sataieva

Żukow

et al. 2018

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Epigenetic transformation of chromatin is able to be induced by environmental factors and changes in the parameters of the state of metabolic processes in the body. Among them, the most common known factors are hypoxia (ischemia of the organ), hyperglycemia, heavy metals, endocrinopathies, infectious diseases. The results of the review conclude that epigenetic mechanisms pay the very important contribution to the restructuring of humoral systems of renal regulation during renal failure sufficiently contributing to a progressive reduction of nephrons and directly preconditioning the unfavorable progress of the disease. In considering this potential etiologic factor, one must take into account several common triggers changing the epigenetic transformation of intrarenal synthesis and metabolism of physiologically active substances. Primary it is the formation of atypical foci of their products, which is most evident in the processes of restructuring of the RAS and nitric oxide systems. Secondary the renal coordinating humoral factors increasingly lose the control of regulation of homeostasis and switch on the pathophysiological way of progressive renal failure. Next are the epigenetic changes of proteins genes that perform key functions in the synthesis and metabolism of humoral factors in the regulation of renal functions. Uncontrolled synthesis of these peptides leads to a triggered enhancement of the process, again, involving epigenetic chromatin rearrangement. The indicated regularity can be traced to unrestricted activation of RAAS and the renal system of TGF-beta. Other contributing factors occur as a result of unrestricted activation of RAAS and the TGF-beta system. On this background, there is a steady decline in the regulatory capabilities of the opposition control vector represented by the nitrogen oxide system, primarily by the constitutive isoforms eNOS and nNOS. The research of epigenetic processes during various nephropathies does not only enlightens theoretical basis for the pathogenesis of renal failure but also opens promising approaches for the development of new pharmacological corrects of renal function. kidneys, renal failure, epigenetics, renin-angiotensin-aldosterone system, transforming growth factor beta, nitric oxide.

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Circular RNAs in Acute Kidney Injury: Roles in Pathophysiology and Implications for Clinical Management

Yap

Chan

2022

IJMS

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Acute kidney injury (AKI) is a common clinical condition, results in patient morbidity and mortality, and incurs considerable health care costs. Sepsis, ischaemia-reperfusion injury (IRI) and drug nephrotoxicity are the leading causes. Mounting evidence suggests that perturbations in circular RNAs (circRNAs) are observed in AKI of various aetiologies, and have pathogenic significance. Aberrant circRNA expressions can cause altered intracellular signalling, exaggerated oxidative stress, increased cellular apoptosis, excess inflammation, and tissue injury in AKI due to sepsis or IRI. While circRNAs are dysregulated in drug-induced AKI, their roles in pathogenesis are less well-characterised. CircRNAs also show potential for clinical application in diagnosis, prognostication, monitoring, and treatment. Prospective observational studies are needed to investigate the role of circRNAs in the clinical management of AKI, with special focus on the safety of therapeutic interventions targeting circRNAs and the avoidance of untoward off-target effects.

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AKI and Genetics: Evolving Concepts in the Genetics of Acute Kidney Injury: Implications for Pediatric AKI

Cited by 3 publications

References 79 publications

Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review

Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review

Ecological aspects of molecular mechanisms of epigenetic rearrangement of humoral systems of the renal function regulation

Circular RNAs in Acute Kidney Injury: Roles in Pathophysiology and Implications for Clinical Management

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