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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sepsis patients | Patients admitted to the intensive care unit with sepsis diagnosed or suspected |
| |
| Surgical patients | Previously healthy patients who are operated for colon cancer with laparoscopic technique. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Para Aminohippurate | Drug | Measurements of renal plasma flow and glomerular filtration rate |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hemodynamics | Systemic and regional hemodynamics | Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolic alterations | Renal arginine metabolism | Repeated measures at 10am, 12am, 2pm, 4pm,6pm, and 8pm |
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Inclusion Criteria sepsis group:
Comparator group
Previously healthy individuals scheduled for laparoscopic colon cancer resection
Normal creatinine levels within 3 months before admittance to hospital.
Exclusion Criteria:
-
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Intensiv care patients Surgical patients
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lars M Ytrebo, MD PhD | Contact | +4790788058 | lars.marius.ytrebo@unn.no |
| Name | Affiliation | Role |
|---|---|---|
| Lars MG Ytrebø | University Hospital of North Norway | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital of North Norway | Recruiting | Tromsø | Troms | 9038 | Norway |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D010130 | p-Aminohippuric Acid |
| D007472 | Iohexol |
| ID | Term |
|---|---|
| D000618 | Aminohippuric Acids |
| D006626 | Hippurates |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 |
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Blood and urine
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| Organic Chemicals |
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D007651 | Keto Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D014283 | Triiodobenzoic Acids |
| D007463 | Iodobenzoates |