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.
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since it has effects on the immune system (reduced expression of cytokines) as well as on tubular epithelial cells (unpublished animal data from our laboratory).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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the investigational drug
Immediately after randomization (not longer than 30 min after fulfilling eligibility criteria), patients will receive intravenous infusions with the placebo
University Hospital Münster
Münster, Germany
Kidney damage after cardiac surgery identified by measuring biomarkers ([TIMP-2]*[IGFBP7]
The presence of tissue inhibitor of metalloproteinases (TIMP-2) and insulin-like grwoth-factor binding protein 7 (IGFBP7) in the urine will be measured.
Time frame: 12 hours after cardiac surgery
Occurence of acute kidney injury according to the KDIGO (Kidney Disease: Improving Global Outcomes) criteria
Time frame: 72 hours after end of cardiac surgery
Severity of acute kidney injury (number of patients with KDIGO stage 1, KDIGO stage 2 or KDIGO stage 3)
Definition and classification of acute injury according to the KDIGO (Kidney Disease Improving Global Outcomes) clinical practice guidelines on acute kidney injury
Time frame: 72 hours after end of cardiac surgery
Creatinine Clearance
Time frame: one day after cardiac surgery
Free-days of vasoactive medications and mechanical ventilation
Time frame: 28 days after cardiac surgery
Renal recovery
Renal recovery is defined as serum creatinine levels \< 0.5 mg/dL higher than baseline serum creatinine
Time frame: 30 days after cardiac surgery
Renal recovery
Renal recovery is defined as serum creatinine levels \< 0.5 mg/dL higher than baseline serum creatinine
Time frame: 60 days after cardiac surgery
Renal recovery
Renal recovery is defined as serum creatinine levels \< 0.5 mg/dL higher than baseline serum creatinine
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Time frame: 90 days after cardiac surgery
Mortality
Time frame: 30 days after cardiac surgery
Mortality
Time frame: 60 days after cardiac surgery
Mortality
Time frame: 90 days after cardiac surgery
ICU and Hospital stay
Time frame: up to 90 days after cardiac surgery (until discharge)
Number of patients with renal replacement therapy
Time frame: up to 90 days after cardiac surgery