Clinical trial NCT05694624: Investigations Into Sepsis-associated Acute Kidney Injury
Official title: Investigations Into the Mechanisms for Bioenergetic Failure in Sepsis-associated Acute Kidney Injury
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Kidney Injury
Lead sponsor: University Hospital of North Norway
Sponsor class: OTHER
First posted: 2023-01-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Intensiv care patients Surgical patients

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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: Hemodynamics
timeFrame: Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm
Secondary outcomes:
measure: Metabolic alterations
timeFrame: Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm
Other outcomes:
Locations:
city: Tromsø
country: Norway
facility: University Hospital of North Norway
state: Troms
Study officials:
affiliation: University Hospital of North Norway
name: Lars MG Ytrebø
role: PRINCIPAL_INVESTIGATOR
References: