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

Silver SA, Cardinal H, Colwell K, Burger D, Dickhout JG - Can J Kidney Health Dis (2015)

Bottom Line: MEDLINE, ISI Web of Science.As such, it does not represent a systematic review of all of the AKI literature.Translation of findings from biomedical research into AKI therapy presents several challenges.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, St. Michael's Hospital, University of Toronto, Toronto, Canada.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

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
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Fig3: 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

Mentions: Cell therapy has shown therapeutic promise in preclinical studies that, if realized clinically, would be transformative within the field of AKI. Nevertheless, uptake of this preclinical innovation has been slow and while the benefits of cell therapy have been established for over a decade, clinical trials are only recently established. While this is likely due in part to a greater burden for regulatory approval, preclinical research has also failed to address several key steps in the optimization of cell-based therapy. First, the most effective population of cells for promoting recovery has not been established through direct comparison of various cell populations. Secondly, isolation procedures have not been standardized and the most appropriate source (i.e. allogeneic vs autologous; peripheral blood vs umbilical cord blood) has not been established. Third, the most effective route and timing of delivery is unclear. Finally, questions of long-term safety have not been adequately addressed, as long-term follow-up has only rarely been done in animal models. Collectively, the failure to address these key steps has led to a paucity of information essential for appropriate trial design, without which therapeutic development is impossible. By contrast, preclinical work examining extracellular vesicles is at a much earlier stage. Because of this, preclinical research has the opportunity to better inform potential clinical studies on extracellular vesicles in AKI through optimization of therapy. Such information would lead to improved design of clinical trials, and a more rapid translation of results through valleys 1 and 2 into clinical practice (see Fig. 3).Fig. 3


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

Silver SA, Cardinal H, Colwell K, Burger D, Dickhout JG - Can J Kidney Health Dis (2015)

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4556308&req=5

Fig3: 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
Mentions: Cell therapy has shown therapeutic promise in preclinical studies that, if realized clinically, would be transformative within the field of AKI. Nevertheless, uptake of this preclinical innovation has been slow and while the benefits of cell therapy have been established for over a decade, clinical trials are only recently established. While this is likely due in part to a greater burden for regulatory approval, preclinical research has also failed to address several key steps in the optimization of cell-based therapy. First, the most effective population of cells for promoting recovery has not been established through direct comparison of various cell populations. Secondly, isolation procedures have not been standardized and the most appropriate source (i.e. allogeneic vs autologous; peripheral blood vs umbilical cord blood) has not been established. Third, the most effective route and timing of delivery is unclear. Finally, questions of long-term safety have not been adequately addressed, as long-term follow-up has only rarely been done in animal models. Collectively, the failure to address these key steps has led to a paucity of information essential for appropriate trial design, without which therapeutic development is impossible. By contrast, preclinical work examining extracellular vesicles is at a much earlier stage. Because of this, preclinical research has the opportunity to better inform potential clinical studies on extracellular vesicles in AKI through optimization of therapy. Such information would lead to improved design of clinical trials, and a more rapid translation of results through valleys 1 and 2 into clinical practice (see Fig. 3).Fig. 3

Bottom Line: MEDLINE, ISI Web of Science.As such, it does not represent a systematic review of all of the AKI literature.Translation of findings from biomedical research into AKI therapy presents several challenges.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, St. Michael's Hospital, University of Toronto, Toronto, Canada.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus