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1 INTRODUCTION The necessity of the topic Use of donated kidneys from patients with brain death is a problem that needs to be developed However, patients with brain death often have changes in the pathophysiology that affect the function of organs in the body Changes due to lack of control from the brain, a lack of circulating volume, the effects of hormonal disorders, inflammatory factors that lead to organ failure, including kidney function Maintaining the function of organs, including kidneys from braindead patients, the best timing for organ removal, is an issue that needs to be studied In our country today, changes in morphology and kidney function in patients with brain death have not been studied fully and comprehensively Therefore, we proceed to the topic “A Study on kidney function and morphology in brain dead patients due to traumatic brain injury” Objectives: Evaluation of some morphological indicators on ultrasound, histopathological damage and renal function changes within 72 hours in patients with brain death due to traumatic brain injury Understanding the relationship and predictive value of acute kidney damage through NGAL and microalbuminuria in brain death patients due to traumatic brain injury Practical significance and contribution of the thesis The thesis is a research project with scientific significance, clinical practical significance, necessary and practical: there exists a high number of brain death patients due to traumatic brain injury The use of kidney transplant resources from patients with brain death is a matter of research and development Maintenance and evaluation of renal function in patients with cerebral death should be investigated Morphological surveillance on ultrasound, histopathology and renal function changes in patients with brain death, the proportion of patients with acute kidney damage: 12 hours after brain death, hemodynamic indicators of renal arteries have changed kidney damage and tissue accounted for 88.9% Patients are presented with polyuria in the first 24 hours after brain death then the condition subsides The concentration of NGAL, microalbuminuria increases, glomerular filtration rate decreases with time of death Renal function is stable in the first 24 hours of brain death and then decreases rapidly It is possible to find a link between some clinical and laboratory indicators in the diagnosis of AKI Based on NGAL concentrations, microalbuminuria can be predicted and prognosed for acute renal damage in patients with brain death due to traumatic brain injury Layout of the thesis The thesis has 126 pages, including the following sections: Introduction (02 pages), literature review (38 pages), research objective and methodology (26 pages), research results (21 pages), discussion (37 pages), limitations of the topic (01 page) conclusions (02 pages), recommendations (01 page) The thesis has 50 tables, 24 pictures, 130 references including in Vietnamese, English and French CHAPTER 1: LITERATURE REVIEW 1.1 TRAUMATIC BRAIN INJURY AND BRAIN DEATH 1.1.1 Traumatic brain injury: Traumatic brain injury is a change in brain function, or other evidences of brain pathology, caused by an external force Changes in brain function are determined by periods of loss or impairment of cognitive ability, memory loss about events that have occurred just before (retrograde amnesia) or after trauma of the nervous system (paralysis, hypoesthesia, dysphasia ) Traumatic brain injury is a common condition Each year in the US there are about 1.5 million cases of traumatic brain injury Traumatic brain injury is a factor that contributes to 30.5% of all injuryrelated deaths in the United States In Vietnam, according to the National Traffic Safety Committee, about 10 000 people die from traffic accidents every year Traumatic brain injury is the leading cause of death and disability of all ages One of the main pathogenetic mechanisms causing severe trauma is cerebral edema and increased intracranial pressure 1.1.2 Brain death in traumatic brain injury patients Brain death is a constant cessation of all brain function, including brain stem’s, also known as total brain death This definition is accepted in most countries throughout the world Brain death is the clinical syndrome of coma, loss of brain stem reflexes, and apnea due to known and irreversible causes The most common cause of brain stem death is traumatic brain injury, brain stroke, brain tumor, brain damage due to lack of oxygen Brain death is a condition where the brain is severely damaged, the brain function stops working and the brain dies cannot be revived (article 3, clause 6, page of Law No 75/2006 / QH11) Brain death diagnosis is based on: + Clinical criteria + Laboratory criteria + Time criteria 1.2 Kidney morphology and function in brain death patients 1.2.1 Kidney morphology Degeneration of renal structure: Glomerular hyperemia, glomerulonephritis and glomerular inflammation, cellular vacuolization, near and far renal tubular atrophy or necrosis, endothelial hyperplasia and glomerular capillaries hyperplasia Increased immunogenicity of the kidneys before transplant: an increase in E-selectin, P-selectin, ICAM-1, VCAM-1 in endothelial cells of 44% of kidney from deceased donor compared to 9% from living donor Increased MHC group II (DR) in renal tubular cells Interstitial cell infiltrates such as T cells, macrophages, neutrophils in 53% of kidneys from deceased donors compared with 0% from living donors The incidence of renal failure and acute tubular necrosis is increased if systolic blood pressure in patients with brain death fluctuates below 80 - 90 mmHg Experiments in animal models show that in patients with brain death, there is damage to the integrity of renal parenchyma (shown by measuring intracellular Na +: K + ratio) Damage to parenchymal cells can be prevented by using T3, cortisol, insulin and ensuring good hemodynamics 1.2.2 Kidney function Effects of hemodynamics: Changes in hemodynamic fluctuations such as strong vasoconstriction associated with reduced cardiac output, hypotension and lack of circulating volume can all lead to renal damage due to decreased renal perfusion The incidence of renal failure and acute tubular necrosis is increased if systolic blood pressure in patients with cerebral death fluctuates below 80 - 90 mmHg Effects of endocrine: Impaired function of the hypothalamus - pituitary system; changes of thyroid hormones Influence of inflammatory factors: Severe brain damage is fueled by local inflammatory response, which can eventually lead to brain death, which then triggers a "sympathetic storm," releasing large amounts of cytokines into the blood, aggravating inflammation 1.2.3 Methods for assessing kidney morphology and renal function Diagnostic imaging methods: Kidney ultrasound, Xray diagnostic of the urinary system, computer tomography of the urinary system, magnetic resonance imaging of the urinary system Kidney biopsy 1.3 Biological markers assessing acute kidney damage 1.3.1 Neutrophil gelatinase-associated lipocalin (NGAL) Neutrophil gelatinase-associated lipocalin (NGAL): is a protein with a molecular weight of 25kD, containing 20 amino acids capable of binding free iron in the body, belonging to the lipocalin family NGAL is an important factor in the immune response to infection, manifested in immune cells, liver cells, renal tubular cells in various medical conditions NGAL has been shown to be the protein of tubular origin that increases at the earliest when there is acute kidney damage due to anemia, decreased renal perfusion, often appearing in urine before other markers When the tubular is damaged, NGAL secreted from tubular cells will drain into the urine, partially absorbed into the blood Increased NGAL levels in blood and urine have been shown to be highly sensitive and specific to predict progression to acute kidney damage 1.3.2 Microalbuminuria Microalbuminuria is a very small amount of albumin excreted by the kidneys in the urine Urine microalbumin levels are greater than normal, indicating kidney damage Urine microalbumin test helps detect kidney disease in early stages Microalbuminuria has long been shown by scientists to be associated with the development of chronic kidney disease in patients with diabetes or hypertension However, its value in predicting acute kidney injury has been poorly reported CHAPTER 2: RESEARCH OBJECT AND METHODOLOGY 2.1 Research object: Patient diagnosed with brain death due to traumatic brain injury, treated at Anesthesia and Intensive Care Center - Viet Duc Hospital and Emergency and Poison Control Center - Military Hospital 103 from December 2012 to January 2019 Inclusion criteria: Traumatic brain injury patients - Be diagnosed with brain death according to the criteria of the Ministry of Health (Decision No 32/2007 / QD-BYT dated August 15, 2007 of the Ministry of Health on promulgating regulations of clinical standards, subclinical standards and cases where clinical criteria are not applicable for brain death determination): + Deep coma, Glasgow Coma Scale: points + The pupils are constantly dilated over 4mm + Loss of pupils light reflexes + Loss of corneal reflexes + Loss of pharyngeal reflexes + Positive doll’s eyes reflex + Loss of vestibulo-ocular reflex + Positive apnea test + Transcranial doppler ultrasound: Doppler waves are not seen or diastolic blood flow is lost, only the early systolic miniature peaks (Vs < 10cm/s) + Criteria for timing: to determine brain death, examine the patient times every hours apart to identify the patient with brain death since the patient has met clinical and irreversible criteria to be declared as brain dead The family agreed to participate in the study Exclusion criteria: Not qualified to diagnose brain death Eligible to diagnose brain death but accompanied by: + History of kidney disease + History of chronic disease: diabetes, hypertension, cancer, + Kidney injury + Infectious diseases: HBV, HIV, HCV, + Patient's family does not agree to participate Criteria for removing patients from the study: The patient was eligible for research but died or his family requested to go home before the study tests were complete 2.2 Research methodology 2.2.1.Research design This is a clinical descriptive prospective study with vertical observation model 2.2.2.Sampling method Convenient sampling, at two hospitals, took all eligible patients for selection during the study period 2.2.3.Drugs and means of research Drugs: Heart failure and vasoconstrictor medications: adrenaline, noradrenaline, dopamine Research facilities and equipment: + Resuscitation facilities: Drager - Germany respirator, Phillip multi-parameter monitor, infusion machine, electric injection pump 10 + Ultrasound machine: 4D E-CUBE Korean color ultrasound machine, which has various features such as abdominal ultrasound, renal ultrasound, vascular ultrasound and transcranial doppler ultrasound + Kidney biopsy kit: A biopsy needle attached to a 16G x15 cm disposable gun, a container containing 10% solution of formol solution + Kits for taking and monitoring the amount of urine: urine (Sonde Foley), pouches and urine measuring devices with measuring lines, test tubes for urine + Urine NGAL testing equipment: NGAL ELISA Kit Sigma - USA + Automated biochemical test system meeting ISO 15189 standard - biochemical laboratory - Military Hospital 103 2.2.4.Research content All patients were informed about their medical history and examined according to a sample of medical records serving the study 2.2.4.1 General characteristics of patients with brain death due to traumatic brain injury Characteristics of age, gender, height, weight, BMI Characteristics of injury structure Cause of injury Time of injury before brain death Brain death time Hemodynamic characteristics of brain-dead patients 20 3.2.4.Characteristics of acute kidney damage in patients with brain death over time Table 3.8 AKI according to KDIGO in patients with brain death Non-AKI AKI Time mark n % n % T0 (n=63) 51 81.0 12 19.0 T1 (n=63) 35 55.6 28 44.4 T2 (n=34) 23.5 26 76.5 T3 (n=11) 9.1 10 90.9 T4 (n=3) 0 03 100 The rate of acute kidney damage increases with brain death At the time of T0, non-AKI accounted for 81%, up to T4, 100% of the patients had AKI 3.3 Understanding the relationship and predictive value for AKI of urine NGAL and microalbumin concentration in patients with brain death due to TBI 3.3.1.Relationship between some characteristics of brain death due to traumatic brain injury and AKI Table 3.9 Relationship between pre-injury time and AKI in patients with brain death due to TBI Non-AKI AKI Time Median Median p n (25% - 75%) n (25% - 75%) mark (hours) (hours) 13.75 (6.67 11.13 (3.84 – 0.46 T0 n=63 51 12 33.50) 21.75) T1 n=63 35 16.00 (6.00 28 10.36 (6.17 – 0.11 21 47.83) 27.60 (5.94 57.20) 18.88) 11.65 (6.00 – 0.32 T2 n=34 26 20.41) 15.50 (3.81 – T3 n=11 01 156.66 10 17.63) The time of injury before brain death in the non-AKI group is higher than that of the AKI group at different times (p> 0.05) Table 3.10 Relationship between urinary NGAL concentration and AKI in patients with brain death due to TBI Non-AKI AKI p Time Median Median mark n (25% - 75%) n (25% -75%) (ng/dL) (ng/dL) T0 49.5 (38.9 –