Investigations Into Sepsis-associated Acute Kidney Injury

Recruiting

• Conditions: Acute Kidney Injury
• Interventions: Drug: Para Aminohippurate

• Registration Number: NCT05694624
• Lead Sponsor: University Hospital of North Norway

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.

Study Timeline

• Study First Submitted: 2022-12-05
• Study First Submitted QC: 2023-01-20
• Study First Posted: 2023-01-23
• Study Start: 2023-08-14
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-18
• Last Update Posted: 2025-03-21
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Surgical patients	Para Aminohippurate	Previously healthy patients who are operated for colon cancer with laparoscopic technique.
Sepsis patients	Para Aminohippurate	Patients admitted to the intensive care unit with sepsis diagnosed or suspected

Primary Outcome Measures

Name	Time	Method
Hemodynamics	Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm	Systemic and regional hemodynamics

Secondary Outcome Measures

Name	Time	Method
Metabolic alterations	Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm	Renal arginine metabolism

Trial Locations

Locations (1)

University Hospital of North Norway; 🇳🇴 Tromsø, Troms, Norway