Investigations Into Sepsis-associated Acute Kidney Injury

Investigations Into the Mechanisms for Bioenergetic Failure in Sepsis-associated Acute Kidney Injury

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: Para Aminohippurate

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 Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Lars M Ytrebo, MD PhD; Phone Number: +4790788058; Email: lars.marius.ytrebo@unn.no

Study Locations

• Norway
  • Troms
    • Tromsø, Troms, Norway, 9038
      • Recruiting
      • University Hospital of North Norway
      • Contact: Lars M Ytrebø, MD PhD; Phone Number: +47 90788058; Email: lars.marius.ytrebo@unn.no
      • Sub-Investigator: Kjellbjorn Jakobsen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Intensiv care patients Surgical patients

Description

Inclusion Criteria sepsis group:

• 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:

-

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sepsis patients; Patients admitted to the intensive care unit with sepsis diagnosed or suspected	Drug: Para Aminohippurate; Measurements of renal plasma flow and glomerular filtration rate; Other Names: iohexol
Surgical patients; Previously healthy patients who are operated for colon cancer with laparoscopic technique.	Drug: Para Aminohippurate; Measurements of renal plasma flow and glomerular filtration rate; Other Names: iohexol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamics	Systemic and regional hemodynamics	Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic alterations	Renal arginine metabolism	Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Investigators: Principal Investigator: Lars MG Ytrebø, University Hospital of North Norway

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 5, 2022
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: Record ID 3055

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No