Investigations Into Sepsis-associated Acute Kidney Injury

NCT ID: NCT05694624

Last Updated: 2025-03-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-08-14
• Study Completion Date: 2026-12-31

Brief Summary

In this study the investigators would like to study systemic and regional disturbances in patients with sepsis-associated acute kidney injury and in healthy controls undergoing laparoscopic abdominal surgery. Specifically study metabolic, hemodynamic and oxygen transport variables.

Detailed Description

Acute kidney injury (AKI) in patients with sepsis has a very poor prognosis with up to 60% mortality. The pathobiology remains to be fully understood. Creatine and phosphocreatine, products of arginine metabolism through L-arginine:glycine amidinotransferase (AGAT) and its sister enzyme guanidinoacetate N-methyl-transferase (GAMT), provide an energy-buffering system that is essential for intracellular adenosine triphosphate (ATP) supply. We hypothesized that sepsis associated AKI may be caused by failure of this energy-buffering system. In series of pilot studies, we explored metabolic and bioenergetic patterns in patients and animals with high risk of developing AKI. These data suggest that sepsis associated AKI may be caused by failure of this alternative renal energy source. In the current application we propose a clinical investigation of renal metabolism and renal bioenergetics in patients with high and low risk of developing sepsis associated AKI. The primary objective is to directly investigate renal AGAT activity through the arginyl metabolites homoarginine, guanidino acetate, and creatine. Secondary objectives are to study renal and systemic hemodynamics, renal oxygenation, glomerular filtration rate (GFR), renal tubular function, and mitochondrial respiration.

Conditions

Acute Kidney Injury

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Sepsis patients

Patients admitted to the intensive care unit with sepsis diagnosed or suspected

Para Aminohippurate

Intervention Type: DRUG

Measurements of renal plasma flow and glomerular filtration rate

Surgical patients

Previously healthy patients who are operated for colon cancer with laparoscopic technique.

Para Aminohippurate

Intervention Type: DRUG

Measurements of renal plasma flow and glomerular filtration rate

Interventions

Para Aminohippurate

Measurements of renal plasma flow and glomerular filtration rate

Intervention Type: DRUG

Other Intervention Names

iohexol

Eligibility Criteria

Inclusion Criteria

• Sepsis diagnosed or suspected
• Normal premorbid serum creatinine measured or anticipated (if data are not available)
• Normovolemia as indicated by a pulse pressure variation less than 12%

Comparator group

• Previously healthy individuals scheduled for laparoscopic colon cancer resection
• Normal creatinine levels within 3 months before admittance to hospital.

• Patients admitted to the intensive care unit with sepsis diagnosed or suspected
• Previously healthy patients listed for elective colon cancer surgery

Exclusion Criteria

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of North Norway

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars MG Ytrebø

Role: PRINCIPAL_INVESTIGATOR

University Hospital of North Norway

Locations

University Hospital of North Norway

Tromsø, Troms, Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Lars M Ytrebo, MD PhD

Role: CONTACT

lars.marius.ytrebo@unn.no

+4790788058

Facility Contacts

Lars M Ytrebø, MD PhD

Role: primary

lars.marius.ytrebo@unn.no

+47 90788058

Other Identifiers

Record ID 3055

Identifier Type: -

Identifier Source: org_study_id