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Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury
Published on: July 17, 2016
The intensive care medicine agenda on acute kidney injury
Peter Pickkers1, Marlies Ostermann2, Michael Joannidis3
1Department of Intensive Care Medicine (710), Radboud University Medical Centre, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Abstract:
Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.
Insights
Acute kidney injury (AKI) impacts critically ill patients, with new biomarkers improving early detection. Research is clarifying AKI
Area of Science:
- Nephrology and Critical Care Medicine
Background:
- Acute kidney injury (AKI) is a frequent complication in critically ill patients.
- Current management focuses on risk identification, hemodynamic support, avoiding nephrotoxins, and renal replacement therapy (RRT).
- Early biomarkers for renal tissue damage offer improved diagnostic capabilities beyond current AKI criteria.
Purpose of the Study:
- To address uncertainties in AKI pathophysiology, treatment, and prognosis.
- To identify priority research areas and clinical endpoints for the next decade.
- To evaluate the long-term consequences of AKI and optimize renal recovery strategies.
Main Methods:
- Review of current literature and established knowledge gaps in AKI.
- Analysis of conflicting research findings regarding AKI treatments and pathologies.
- Proposal of future clinical trials and research priorities based on identified uncertainties.
Main Results:
- Challenged traditional beliefs about AKI pathology (e.g., acute tubular necrosis, septic AKI mechanisms).
- Highlighted conflicting evidence on interventions like fluid therapy, vasopressors, and RRT dosing.
- Emphasized the long-term impact of AKI episodes beyond hospitalization.
Conclusions:
- Significant knowledge gaps remain regarding AKI's aetiology, clinical context, and management.
- Future research must prioritize biomarker-driven interventions, optimal RRT strategies, and renal recovery assessment.
- Defining appropriate clinical endpoints is crucial for advancing AKI care and improving patient outcomes.
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