Acute Kidney Injury, Cardiac Surgery
Conditions
Keywords
Cardiac surgery, glutamine
Brief summary
The aim of this study is to evaluate whether the application of glutamine versus control in patients with high risk for AKI identified by biomarkers can reduce kidney damage after cardiac surgery.
Detailed description
Cardiac surgery is characterized by an increased production of free radicals as a consequence of surgical trauma, ischemia-reperfusion injury, inflammatory response syndrome in response to the use of the extracorporeal circulation. This results in an increased production and release of free radicals which may lead to an exhaustion of antioxidants and organ failure since the lungs, kidneys, liver and gastrointestinal tract are particularly susceptible to reactive oxidant species. Glutamine is considered as a conditionally indispensable amino acid in catabolic states of critically ill patients. It belongs, together with other mediators, to the host defense as major intracellular direct free radical scavengers. Its depletion has been demonstrated to be an independent predictor of mortality in a group of ICU (intensive care unit) patients. Clinical studies showed a positive outcome effect. In animal models, glutamine reduces the occurrence of AKI after ischemia-reperfusion injury. This could be demonstrated through reduced functional markers as well as reduced renal biomarker levels. Preliminary data suggest that glutamine has pleiotropic effects since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory). Thus, a randomized-controlled trial to analyze the effects of glutamine supplementation in high risk patients identified by renal biomarkers undergoing cardiac surgery with cardiopulmonary bypass (CPB) on the effects of kidney damage is urgently needed.
Interventions
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the investigational drug
DRUGPlacebo
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo
Sponsors
Fresenius Kabi
IZKF (Interdisciplinary Centre for Clinical Research (IZKF), Muenster)
University Hospital Muenster
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients undergoing cardiac surgery with CPB * Urinary \[TIMP-2\]\*\[IGFBP7\] \>= 0.3 4h after CPB * Written informed consent
Exclusion criteria
* Preexisting AKI (stage 1 and higher) * Patients with cardiac assist devices * Pregnant women, nursing women and women of childbearing potential * Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis * Chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) \< 30 ml/min * Dialysis dependent CKD * Prior kidney transplant within the last to 12 months * Hypersensitivity to the active substance, or to any of the excipients of the study medication * Hepatic insufficiency * Severe metabolic acidosis (pH \< 7.2) * Participation in another intervention trial in the past 3 months * Persons with any kind of dependency on the investigator or employed by the institution responsible or investigator * Persons held in an institution by legal or official order
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7] | 12 hours after cardiac surgery | The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like grwoth-factor binding protein 7 (IGFBP7) in the urine will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of acute kidney injury (number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3) | 72 hours after end of cardiac surgery | Definition and classification of acute injury according to the KDIGO (Kidney Disease Improving Global Outcomes) clinical practice guidelines on acute kidney injury |
| Creatinine Clearance | one day after cardiac surgery | — |
| Free-days of vasoactive medications and mechanical ventilation | 28 days after cardiac surgery | — |
| Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria | 72 hours after end of cardiac surgery | — |
| Mortality | 30 days after cardiac surgery | — |
| ICU and Hospital stay | up to 90 days after cardiac surgery (until discharge) | — |
| Number of patients with renal replacement therapy | up to 90 days after cardiac surgery | — |
| Renal recovery | 30 days after cardiac surgery | Renal recovery is defined as serum creatinine levels \< 0.5 mg/dL higher than baseline serum creatinine |
Countries
Germany
Outcome results
None listed