Efficacy of Leveraging Endocrine Therapies for Renoprotection during Intensive Care

Informations projet

ELECTRIC

N° de convention de subvention: 101024833

DOI

10.3030/101024833

Projet clôturé

Date de signature de la CE 21 Avril 2021

Date de début 1 Juin 2021

Date de fin 31 Mai 2024

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 277 259,52

Contribution de l’UE

€ 277 259,52

Coordonné par

STICHTING AMSTERDAM UMC
Netherlands

Periodic Reporting for period 2 - ELECTRIC (Efficacy of Leveraging Endocrine Therapies for Renoprotection during Intensive Care)

Période du rapport: 2023-06-01 au 2024-05-31

Résumé du contexte et des objectifs généraux du projet

Problem/Issue Being Addressed: This project targets acute kidney injury (AKI) in ICU patients, specifically in sepsis or cardiac surgery cases. AKI affects over 50% of ICU patients and is associated with high mortality and long-term morbidity. Currently, AKI is diagnosed by renal function deterioration using plasma creatinine or urine output. The exact cause of AKI is unclear, but renal medulla hypoxia is thought to play a key role.

Why is it Important for Society? AKI in the ICU is a significant issue, with serious consequences, including high mortality and potential progression to end-stage renal disease. Improving AKI prevention and management is critical to enhancing ICU care, reducing healthcare burdens, and saving lives.

Overall Objectives: The project aims to evaluate the effectiveness of two renoprotective agents—GLP-1 receptor agonists (GLP-1 RA) and SGLT2 inhibitors (SGLT2i)—in preventing and reducing AKI in the ICU. The key objectives are:

Assess GLP-1 receptor activation and SGLT2 inhibition effects on kidney perfusion, oxygenation, and injury markers in an ovine septic shock-induced AKI model.
Evaluate SGLT2i effects on kidney perfusion and oxygenation using imaging in healthy humans.
Examine SGLT2i impact on AKI markers in cardiac surgery patients.

Conclusions of this Action: WP1+2. GLP-1 and SGLT2i did not show renoprotective effects in an ovine sepsis-AKI model. Sepsis-induced AKI may be too severe for these treatments. 3. Long-term SGLT2i treatment in diabetic patients improved kidney perfusion and oxygenation. 4. Short-term SGLT2i before and after cardiac surgery reduced postoperative AKI risk. A large multicenter trial has been initiated.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

WP1 and WP2: Two preclinical studies on sepsis-induced AKI were conducted in collaboration with the Florey Institute. Data collection is complete, and two studies are in the final stages of preparation for publication. Both treatment and placebo groups showed similar rates of renal failure. Papers are expected to be submitted by the year’s end.

WP3: An imaging study in healthy volunteers was completed in collaboration with VUmc. Radiological data from CT and MRI scans are currently being analyzed.

WP4: A clinical trial with 60 cardiac surgery patients was conducted at Amsterdam UMC. The intervention group showed a 50% reduction in AKI incidence within 5 days post-surgery. Blood sample analysis is underway, and manuscript preparation has begun.

Substantial progress has been made across all work packages, with promising results, particularly in WP4’s reduction of AKI incidence. The team is finalizing publications and data analysis.

Overview of exploitation and dissemination
Peer-reviewed publications: 2 completed, 2 expected in 2025
Conference presentations: 2, 1 upcoming in 2025
Conference participations: 4
Organized conferences: 2
Website: 1
Workshops: 1 participation, 1 organization

WP1+2: Presented at EASD 2023; published in Journal of Intensive Care Medicine Experimental.
WP3: Pending publication.
WP4: Presented at ERA 2024, submitted to British Journal of Anaesthesia. Second article published.
Invited to speak at the Translation Intensive Care Medicine Meeting in November 2024.

Secondment
The secondment phase focused on WP3 at VU Medical Centre. Imaging analysis was completed, and additional blood sample analysis is being conducted in collaboration with a lab in Toronto. A report will be submitted to a leading medical journal once all analyses are finished.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Advanced Imaging Techniques: Our collaboration with the radiology department has advanced imaging methods to assess kidney perfusion and oxygenation in healthy individuals, offering deeper insights into renal function beyond traditional diagnostics.

Clinical Trial Findings: The clinical trial demonstrated a 50% reduction in AKI incidence following cardiac surgery in the intervention group, surpassing current clinical outcomes.

Expected Results Until the End of the Project
Publications: Expected publications of preclinical studies in WP1 and WP2 on the effects of GLP-1 RA and SGLT2i on sepsis-induced AKI.
Radiological Data Analysis: Insights into how our interventions affect kidney perfusion and oxygenation in healthy individuals.
Potential Impacts
Improved AKI Prevention and Management: Our research may lead to better strategies for preventing and managing AKI. The 50% reduction in AKI in the clinical trial could greatly benefit patients.

Advanced Diagnostic Tools: Introducing a urinary oxygenation monitor could provide a novel tool for early AKI detection, improving care and reducing costs.

Scientific Advancements: Our preclinical models and imaging techniques add to the knowledge of AKI, fostering further innovation.

Multicenter Study and Clinical Applications: The ongoing multicenter trial demonstrates the scalability of our findings for broader clinical impact.

WP1 Preliminary results