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Review
. 2015 Sep 1:2:30.
doi: 10.1186/s40697-015-0062-9. eCollection 2015.

Acute kidney injury: preclinical innovations, challenges, and opportunities for translation

Samuel A Silver  1 , Héloise Cardinal  2 , Katelyn Colwell  3 , Dylan Burger  4 , Jeffrey G Dickhout  5
Affiliations
Review

Acute kidney injury: preclinical innovations, challenges, and opportunities for translation

Samuel A Silver et al. Can J Kidney Health Dis. .

Abstract
in English, French

Background: Acute kidney injury (AKI) is a clinically important condition that has attracted a great deal of interest from the biomedical research community. However, acute kidney injury AKI research findings have yet to be translated into significant changes in clinical practice.

Objective: This article reviews many of the preclinical innovations in acute kidney injury AKI treatment, and explores challenges and opportunities to translate these finding into clinical practice.

Sources of information: MEDLINE, ISI Web of Science.

Findings: This paper details areas in biomedical research where translation of pre-clinical findings into clinical trials is ongoing, or nearing a point where trial design is warranted. Further, the paper examines ways that best practice in the management of AKI can reach a broader proportion of the patient population experiencing this condition.

Limitations: This review highlights pertinent literature from the perspective of the research interests of the authors for new translational work in AKI. As such, it does not represent a systematic review of all of the AKI literature.

Implications: Translation of findings from biomedical research into AKI therapy presents several challenges. These may be partly overcome by targeting populations for interventional trials where the likelihood of AKI is very high, and readily predictable. Further, specific clinics to follow-up with patients after AKI events hold promise to provide best practice in care, and to translate therapies into treatment for the broadest possible patient populations.

Contexte: L’insuffisance rénale aiguë (IRA), état pathologique important du point de vue clinique, suscite beaucoup d’intérêt dans le milieu de la recherche biomédicale. On tarde toutefois à transposer les conclusions des recherches sur ce sujet en modifications substantielles dans la pratique clinique.

Objectifs: Le présent article passe en revue nombre d’innovations précliniques dans le traitement de l’IRA et explore les défis que pose la transposition des conclusions dans la pratique clinique, ainsi que les occasions d’y parvenir.

Sources d’informations: MEDLINE, ISI Web of Science.

Conclusion: Le présent rapport expose en détail les domaines de la recherche biomédicale dans lesquels les conclusions précliniques sont actuellement transposées ou au point où des essais cliniques seront bientôt justifiés. De plus, le rapport examine des façons d’étendre le recours aux pratiques exemplaires dans la gestion de l’IRA à un plus grand nombre de patients atteints de cette pathologie.

Limites de l’étude: La présente étude fait état de la littérature du point de vue des champs d'intérêt de recherche des auteurs pour le travail de transposition en IRA. Elle ne se veut toutefois pas un compte rendu exhaustif de la littérature scientifique sur l’IRA.

Répercussions: La transposition des conclusions de la recherche biomédicale en traitement de l’IRA pose de nombreux défis. Ceux-ci peuvent être partiellement surmontés en effectuant des essais interventionnels sur des populations ciblées parmi lesquelles l’incidence d’IRA est très élevée et prévisible. De plus, le suivi par des cliniques spécifiques des patients à la suite d’un épisode d’IRA semble prometteur dans le cadre de l’adoption de pratiques exemplaires et de la transposition des thérapies en traitements pour le plus grand bassin de patients possible.

Keywords: Acute kidney injury; Endoplasmic reticulum stress; Kidney transplant; Stem cells; Translational research.

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Figures

Fig. 1
Fig. 1
Bridging the "Death Valleys" of the Canadian healthcare landscape. Depiction of the barriers to putting research into practice in the Canadian healthcare landscape. In order to ensure that the system is sustainable and to enhance health outcomes, it is critical to bridge the gap between research and clinical practice. Valley 1 depicts the limited ability to translate information from basic biomedical research to clinical science and knowledge. Valley 2 depicts the inadequacy of the current healthcare system in synthesizing, disseminating and integrating research results into clinical practice and healthcare decision-making. To bridge the "Death Valleys" of the healthcare landscape, collective engagement in the strategy from all levels of government and the research community is necessary
Fig. 2
Fig. 2
Acute kidney injury due to acute tubular necrosis. Acute tubular necrosis can be the result of nephrotoxins or ischemia to the kidney. Nephrotoxic drugs, such as tunicmycin, can induce ER stress caused by protein misfolding; while a lack of blood supply to the kidney can cause oxidative stress in the mitochondria. Both ER stress and oxidative stress have been shown to generate reactive oxygen species, ultimately leading to acute kidney injury
Fig. 3
Fig. 3
Steps to translate regenerative therapy for acute kidney injury into clinical practice. Cell-based therapy faces a number of unique barriers to be overcome in order to translate research into clinical practice. Firstly, the most effective population of cells to use for therapy is unclear. While beneficial effects have been reported from various cell populations, there is a need for comparisons of efficacy across different cell types. Second, the optimum cell isolation procedure has yet to be identified. Next, the optimum route of cell delivery and timing of delivery in order to promote recovery is unknown. In order to bring acute kidney injury therapy to a new level through regenerative medicine, effectiveness of cell-based treatments must be proven superior to treatment methods currently in use. The final step addresses long-term follow-up with subjects to ensure safety of cell based therapy
See this image and copyright information in PMC

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