Periodic Reporting for period 1 - ELECTRIC (Efficacy of Leveraging Endocrine Therapies for Renoprotection during Intensive Care)
Reporting period: 2021-06-01 to 2023-05-31
Problem/Issue Being Addressed:
The project aims to tackle the critical problem of acute kidney injury (AKI) in the intensive care unit (ICU), specifically focusing on cases related to sepsis or cardiac surgery. AKI is a prevalent and severe condition, with over 50% of ICU patients either experiencing or developing AKI during their stay. This condition has a profound impact on patient health, leading to high short-term mortality rates and long-term morbidity. Currently, AKI is diagnosed through the acute deterioration of renal function, often assessed using plasma creatinine or urine output. The underlying pathophysiology of AKI remains uncertain, but hypoxia of the renal medulla is considered a central factor in its development.
Why is it Important for Society?
The significance of addressing AKI in the ICU cannot be understated. It affects a substantial portion of critically ill patients and leads to devastating consequences, including high mortality rates and the risk of progression to end-stage renal disease for survivors. Improving the prevention and management of AKI is essential for enhancing the overall quality of care in ICUs, reducing the burden on healthcare systems, and ultimately saving lives.
Overall Objectives:
The project's overarching goal is to investigate the effectiveness of two new renoprotective agents, glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i), in preventing and mitigating AKI in the ICU. To achieve this, the project outlines the following research objectives:
Quantify the effect of GLP-1 receptor activation and SGLT2 inhibition on kidney perfusion and oxygenation, as well as markers of kidney injury, in an ovine model of septic shock-associated acute kidney injury.
This objective involves conducting research in animal models to understand how these agents impact kidney function and injury in the context of septic shock.
Evaluate the effect of SGLT2 inhibition on radiologic imaging of kidney perfusion and oxygenation in healthy humans.
This objective seeks to assess the effects of SGLT2 inhibitors on kidney health using non-invasive radiologic imaging techniques in healthy individuals.
Determine the effect of SGLT2i on AKI markers in patients undergoing cardiovascular surgery.
The project aims to tackle the critical problem of acute kidney injury (AKI) in the intensive care unit (ICU), specifically focusing on cases related to sepsis or cardiac surgery. AKI is a prevalent and severe condition, with over 50% of ICU patients either experiencing or developing AKI during their stay. This condition has a profound impact on patient health, leading to high short-term mortality rates and long-term morbidity. Currently, AKI is diagnosed through the acute deterioration of renal function, often assessed using plasma creatinine or urine output. The underlying pathophysiology of AKI remains uncertain, but hypoxia of the renal medulla is considered a central factor in its development.
Why is it Important for Society?
The significance of addressing AKI in the ICU cannot be understated. It affects a substantial portion of critically ill patients and leads to devastating consequences, including high mortality rates and the risk of progression to end-stage renal disease for survivors. Improving the prevention and management of AKI is essential for enhancing the overall quality of care in ICUs, reducing the burden on healthcare systems, and ultimately saving lives.
Overall Objectives:
The project's overarching goal is to investigate the effectiveness of two new renoprotective agents, glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose transport protein 2 inhibitors (SGLT2i), in preventing and mitigating AKI in the ICU. To achieve this, the project outlines the following research objectives:
Quantify the effect of GLP-1 receptor activation and SGLT2 inhibition on kidney perfusion and oxygenation, as well as markers of kidney injury, in an ovine model of septic shock-associated acute kidney injury.
This objective involves conducting research in animal models to understand how these agents impact kidney function and injury in the context of septic shock.
Evaluate the effect of SGLT2 inhibition on radiologic imaging of kidney perfusion and oxygenation in healthy humans.
This objective seeks to assess the effects of SGLT2 inhibitors on kidney health using non-invasive radiologic imaging techniques in healthy individuals.
Determine the effect of SGLT2i on AKI markers in patients undergoing cardiovascular surgery.
Work Package 1 (WP1) and Work Package 2 (WP2):
In collaboration with the Florey Institute in Melbourne, Australia, we conducted two preclinical studies using an ovine model to investigate sepsis-induced acute kidney injury (AKI). Data collection was successfully completed, and we have drafted two comprehensive studies. The co-authors and I are currently in the final stages of preparing both publications for submission. It's important to note that while the results from both studies are intriguing, we observed some impact on kidney function. Nevertheless, it's noteworthy that sepsis-induced renal failure occurred at similar rates and severity in both the treatment groups and the placebo group. We are planning to submit both papers for publication by the end of this year.
Work Package 3 (WP3):
Within Work Package 3, I collaborated closely with colleagues from the radiology and internal medicine departments at VUmc. We successfully conducted an imaging study involving healthy volunteers. The study's final patient visit was completed two months ago. Currently, we are diligently analyzing the radiological data derived from CT and MRI scans of the kidneys before and after treatment. This phase of data processing and analysis is particularly crucial due to the advanced imaging methodology employed.
Work Package 4 (WP4):
In Work Package 4, we carried out a clinical pilot trial involving 60 patients undergoing cardiac surgery at Amsterdam UMC, location AMC. The last patient's final visit has been concluded, and blood samples for analysis are currently undergoing laboratory assessments. The clinical data collected in this trial have been especially noteworthy. We observed a 50% reduction in the incidence of AKI within the first 5 days after surgery in the intervention group compared to the placebo group. Based on the analysis of blood sample results, we are preparing to initiate the manuscript preparation phase for this project.
Overall, substantial progress has been achieved across various work packages of the project. Preclinical studies, imaging investigations, and clinical trials have been successfully conducted, yielding promising results, particularly in reducing the incidence of AKI within the intervention group of the WP4 trial. The research team is actively engaged in the finalization of publications and data analysis, reflecting significant advancements toward accomplishing the project's objectives.
In collaboration with the Florey Institute in Melbourne, Australia, we conducted two preclinical studies using an ovine model to investigate sepsis-induced acute kidney injury (AKI). Data collection was successfully completed, and we have drafted two comprehensive studies. The co-authors and I are currently in the final stages of preparing both publications for submission. It's important to note that while the results from both studies are intriguing, we observed some impact on kidney function. Nevertheless, it's noteworthy that sepsis-induced renal failure occurred at similar rates and severity in both the treatment groups and the placebo group. We are planning to submit both papers for publication by the end of this year.
Work Package 3 (WP3):
Within Work Package 3, I collaborated closely with colleagues from the radiology and internal medicine departments at VUmc. We successfully conducted an imaging study involving healthy volunteers. The study's final patient visit was completed two months ago. Currently, we are diligently analyzing the radiological data derived from CT and MRI scans of the kidneys before and after treatment. This phase of data processing and analysis is particularly crucial due to the advanced imaging methodology employed.
Work Package 4 (WP4):
In Work Package 4, we carried out a clinical pilot trial involving 60 patients undergoing cardiac surgery at Amsterdam UMC, location AMC. The last patient's final visit has been concluded, and blood samples for analysis are currently undergoing laboratory assessments. The clinical data collected in this trial have been especially noteworthy. We observed a 50% reduction in the incidence of AKI within the first 5 days after surgery in the intervention group compared to the placebo group. Based on the analysis of blood sample results, we are preparing to initiate the manuscript preparation phase for this project.
Overall, substantial progress has been achieved across various work packages of the project. Preclinical studies, imaging investigations, and clinical trials have been successfully conducted, yielding promising results, particularly in reducing the incidence of AKI within the intervention group of the WP4 trial. The research team is actively engaged in the finalization of publications and data analysis, reflecting significant advancements toward accomplishing the project's objectives.
Progress Beyond the State of the Art:
Our project has made significant strides beyond the current state of the art in the field of acute kidney injury (AKI) research.
Advanced Imaging Techniques: Our collaboration with the radiology department has leveraged advanced imaging techniques to assess kidney perfusion and oxygenation in healthy individuals. This goes beyond conventional diagnostic methods and contributes to a deeper understanding of renal function.
Clinical Trial Findings: In our clinical pilot trial involving patients undergoing cardiac surgery, we have observed a 50% reduction in AKI incidence in the intervention group within the first 5 days after surgery. This result surpasses existing clinical outcomes and suggests the potential effectiveness of the treatments under investigation.
Expected Results Until the End of the Project: As we progress towards we anticipate several key results:
Publications: We expect to publish the outcomes of our preclinical studies conducted in WP1 and WP2. These publications will provide insights into the effects of GLP-1 RA and SGLT2i on sepsis-induced AKI and contribute valuable knowledge to the scientific community.
Radiological Data Analysis: The analysis of radiological data from WP3 will likely yield insights into the impact of our interventions on kidney perfusion and oxygenation in healthy individuals.
Potential Impacts:
Our project's progress beyond the state of the art, expected results, and potential impacts collectively aim to address a critical healthcare challenge, ultimately improving the prevention, diagnosis, and management of acute kidney injury. The achievement of expected results hold the potential for significant impacts:
Improved AKI Prevention and Management: Our research may lead to the development of more effective strategies for preventing and managing AKI. The 50% reduction in AKI incidence observed in our clinical trial could have profound implications for patients.
Advanced Diagnostic Tools: The deployment of the urinary oxygenation monitor could introduce a novel diagnostic tool for early AKI detection in clinical practice, enhancing patient care and potentially reducing healthcare costs.
Scientific Advancements: Our preclinical models and advanced imaging techniques contribute to the scientific knowledge base surrounding AKI, paving the way for further research innovations.
Multicenter Study and Clinical Applications: The initiation of a follow-up multicenter study demonstrates the scalability and potential translation of our findings into broader clinical applications, benefiting a larger patient population.
Our project has made significant strides beyond the current state of the art in the field of acute kidney injury (AKI) research.
Advanced Imaging Techniques: Our collaboration with the radiology department has leveraged advanced imaging techniques to assess kidney perfusion and oxygenation in healthy individuals. This goes beyond conventional diagnostic methods and contributes to a deeper understanding of renal function.
Clinical Trial Findings: In our clinical pilot trial involving patients undergoing cardiac surgery, we have observed a 50% reduction in AKI incidence in the intervention group within the first 5 days after surgery. This result surpasses existing clinical outcomes and suggests the potential effectiveness of the treatments under investigation.
Expected Results Until the End of the Project: As we progress towards we anticipate several key results:
Publications: We expect to publish the outcomes of our preclinical studies conducted in WP1 and WP2. These publications will provide insights into the effects of GLP-1 RA and SGLT2i on sepsis-induced AKI and contribute valuable knowledge to the scientific community.
Radiological Data Analysis: The analysis of radiological data from WP3 will likely yield insights into the impact of our interventions on kidney perfusion and oxygenation in healthy individuals.
Potential Impacts:
Our project's progress beyond the state of the art, expected results, and potential impacts collectively aim to address a critical healthcare challenge, ultimately improving the prevention, diagnosis, and management of acute kidney injury. The achievement of expected results hold the potential for significant impacts:
Improved AKI Prevention and Management: Our research may lead to the development of more effective strategies for preventing and managing AKI. The 50% reduction in AKI incidence observed in our clinical trial could have profound implications for patients.
Advanced Diagnostic Tools: The deployment of the urinary oxygenation monitor could introduce a novel diagnostic tool for early AKI detection in clinical practice, enhancing patient care and potentially reducing healthcare costs.
Scientific Advancements: Our preclinical models and advanced imaging techniques contribute to the scientific knowledge base surrounding AKI, paving the way for further research innovations.
Multicenter Study and Clinical Applications: The initiation of a follow-up multicenter study demonstrates the scalability and potential translation of our findings into broader clinical applications, benefiting a larger patient population.