Melatonin and the Brain-Heart Crosstalk in Neurocritically Ill Patients-From Molecular Action to Clinical Practice.

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain-heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.

Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury.

Hyperosmotic therapy is commonly used to treat intracranial hypertension in traumatic brain injury patients. Unfortunately, hyperosmolality also affects other organs. An increase in plasma osmolality may impair kidney, cardiac, and immune function, and increase blood-brain barrier permeability. These effects are related not only to the type of hyperosmotic agents, but also to the level of hyperosmolality. The commonly recommended osmolality of 320 mOsm/kg H2O seems to be the maximum level, although an increase in plasma osmolality above 310 mOsm/kg H2O may already induce cardiac and immune system disorders. The present review focuses on the adverse effects of hyperosmolality on the function of various organs.

Implementation of Computed Tomography Angiography (CTA) and Computed Tomography Perfusion (CTP) in Polish Guidelines for Determination of Cerebral Circulatory Arrest (CCA) during Brain Death/Death by Neurological Criteria (BD/DNC) Diagnosis Procedure.

BACKGROUND: Brain death/death by neurologic criteria (BD/DNC) guidelines are routinely analyzed, compared and updated in the majority of countries and are later implemented as national criteria. At the same time, extensive works have been conducted in order to unify clinical procedures and to validate and implement new technologies into a panel of ancillary tests. Recently evaluated computed tomography angiography and computed tomography perfusion (CTA/CTP) seem to be superior to traditionally used digital subtraction angiography (DSA), transcranial Doppler (TCD) and cerebral perfusion scintigraphy for diagnosis of cerebral circulatory arrest (CCA). In this narrative review, we would like to demonstrate scientific evidence supporting the implementation of CTA/CTP in Polish guidelines for BD/DNC diagnosis. Research and implementation process: In the first of our base studies concerning the potential usefulness of CTA/CTP for the confirmation of CCA during BD/DNC diagnosis procedures, we showed a sensitivity of 96.3% of CTA in a group of 82 patients. CTA was validated against DSA in this report. In the second study, CTA showed a sensitivity of 86% and CTP showed a sensitivity of 100% in a group of 50 patients. In this study, CTA and CTP were validated against clinical diagnosis of BD/DNC supported by TCD. Additionally, we propose our CCA criteria for CTP test, which are based on ascertainment of cerebral blood flow (CBF) < 10 mL/100 g/min and cerebral blood volume < 1 mL/100 g in regions of interest (ROIs) localized in all brain regions. Based on our research results, CTA/CTP methods were implemented in Polish BD/DNC criteria. To our knowledge, CTP was implemented for the first time in national guidelines. CONCLUSIONS: CTA and CTP-derived CTA might be in future the tests of choice for CCA diagnosis, proper and/or Doppler pretest might significantly increase sensitivity of CTA in CCA diagnosis procedures. Whole brain CTP might be decisive in some cases of inconclusive CTA. Implementation of CTA/CTP in the Polish BD/DNC diagnosis guidelines does not show any major obstacles. We believe that in next edition of "The World Brain Death Project" CTA and CTP will be recommended as ancillary tests of choice for CCA confirmation during BD/DNC diagnosis procedures.

Atypical Pupil Reactions in Brain Dead Patients.

BACKGROUND: During routine diagnosis of brain death, changes in pupil diameter in response to the stimulation of peripheral nerves are sometimes observed. For example, pupillary dilation after diagnosed brain death is described in the literature as the ciliospinal reflex. However, pupil constriction creates diagnostic doubts. OBJECTIVE: The pupillometric analysis of pupil response to stimulation of the cervicothoracic spinal cord in patients with diagnosed brain death. METHODS: Instrumental tests to confirm the arrest of cerebral circulation were performed in 30 adult subjects (mean age 53.5 years, range 26-75 years) with diagnosed brain death. In addition, a pupillometer was used to measure the change in pupil diameter in response to neck flexion. INTERVENTION: Flexion of the neck and measuring the response in change of the pupil with the use of the pupillometer. RESULTS: The change in the pupil was observed in the examined group of patients. Difference in pupil size ≥ 0.2 mm was observed in 14 cases (46%). In five cases (17%), pupil constriction was found (from 0.2 to 0.7 mm). Measurement error was +/- 0.1 mm. CONCLUSIONS: Both pupillary constriction and dilatation may occur due to a ciliospinal reflex in patients with brain death. This phenomenon needs further research in order to establish its pathophysiology.

Invitation to participate in a multi-center study for validation of cerebral computed tomography angiography and computed tomography perfusion in the determination of cerebral circulatory arrest during brain death/death by neurological criteria diagnosis procedure in paediatric population below 12 years of age.

We would like to invite paediatric intensive care units (PICU) to join our multi-center trial concerning patient population < 12 y/o and aiming at: • validation of computed tomography angiography (CTA)/computed tomography perfusion (CTP) tests for brain death/death by neurological criteria (BD/DNC) diagnosis procedures, • validation of duplex Doppler insonation of extracranial segments of the internal cerebral arteries and the vertebral arteries for choosing an optimal time for CTA/CTP testing.

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of the Ligands of Receptors CCR1, CCR2, CCR3, and CCR4.

CC chemokines, a subfamily of 27 chemotactic cytokines, are a component of intercellular communication, which is crucial for the functioning of the tumor microenvironment. Although many individual chemokines have been well researched, there has been no comprehensive review presenting the role of all known human CC chemokines in the hallmarks of cancer, and this paper aims at filling this gap. The first part of this review discusses the importance of CCL1, CCL3, CCL4, CCL5, CCL18, CCL19, CCL20, CCL21, CCL25, CCL27, and CCL28 in cancer. Here, we discuss the significance of CCL2 (MCP-1), CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL22, CCL23, CCL24, and CCL26. The presentation of each chemokine includes its physiological function and then the role in tumor, including proliferation, drug resistance, migration, invasion, and organ-specific metastasis of tumor cells, as well as the effects on angiogenesis and lymphangiogenesis. We also discuss the effects of each CC chemokine on the recruitment of cancer-associated cells to the tumor niche (eosinophils, myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), regulatory T cells (Treg)). On the other hand, we also present the anti-cancer properties of CC chemokines, consisting in the recruitment of tumor-infiltrating lymphocytes (TIL).

The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients.

INTRODUCTION: Neutrophil-lymphocyte count ratio (NLCR) is a simple and low-cost marker of inflammatory response. NLCR has shown to be a sensitive marker of clinical severity in inflammatory-related tissue injury, and high value of NLCR is associated with poor outcome in traumatic brain injured (TBI) patients. The purpose of this study was to retrospectively analyze NLCR and its association with outcome in a cohort of TBI patients in relation to the type of brain injury. METHODS: Adult patients admitted for isolated TBI with Glasgow Coma Score lower than eight were included in the study. NLCR was calculated as the ratio between the absolute neutrophil and lymphocyte count immediately after admission to the hospital, and for six consecutive days after admission to the intensive care unit (ICU). Brain injuries were classified according to neuroradiological findings at the admission computed tomography (CT) as DAI-patients with severe diffuse axonal injury; CE-patients with hemispheric or focal cerebral edema; ICH-patients with intracerebral hemorrhage; S-EH/SAH-patients with subdural and/or epidural hematoma/subarachnoid hemorrhage. RESULTS: NLCR was calculated in 144 patients. Admission NLCR was significantly higher in the non-survivors than in those who survived at 28 days (p < 0.05) from admission. Persisting high NLCR value was associated with poor outcome, and admission NLCR higher than 15.63 was a predictor of 28-day mortality. The highest NLCR value at admission was observed in patients with DAI compared with other brain injuries (p < 0.001). Concussions: NLCR can be a useful marker for predicting outcome in TBI patients. Further studies are warranted to confirm these results.

Comparison of Two Apnea Test Methods, Oxygen Insufflation and Continuous Positive Airway Pressure During Diagnosis of Brain Death: Final Report.

INTRODUCTION: Deterioration of the pulmonary function after the apnea test (AT) conducted with the classic oxygen insufflation AT (I-AT) is often observed during the brain death (BD) diagnosis procedure. In the present study, two AT methods were compared before a method is recommended for the currently revised Polish BD criteria. METHODS: Classic I-AT and continuous positive airway pressure AT (CPAP-AT) were performed in 60 intensive care unit patients. I-AT was performed at the end of two series of clinical tests, and approximately 1-1.5 h later, after BD was confirmed, a different method, CPAP-AT with 100% FiO2 and CPAP value of 10 cm H2O provided by a ventilator in CPAP mode was performed. The patients in I-AT and CPAP-AT groups were further divided into two subgroups: non-hypoxemic (NH) with good lung function before AT (PaO2/FiO2 index ≥ 200 mmHg) and hypoxemic (H) with poor lung function (PaO2/FiO2 index < 200 mmHg). PaO2 and PaCO2 were recorded prior to I-AT and CPAP-AT at time-point one (T1), 5 min after each test at time-point two (T2), and after 10 min prior to the end of tests at time-point three (T3). The I-AT NH subgroup consisted of 50 patients, and CPAP-AT NH subgroup 43 patients. The I-AT H subgroup consisted of 10 patients, and the CPAP-AT H subgroup 17 patients. RESULTS: In the I-AT NH subgroup, a gradual decrease in PaO2/FiO2 was observed throughout the AT but not in the CPAP-AT NH subgroup. The PaO2/FiO2 ratio during the AT in the CPAP-AT H group was stable with a slight tendency to increase but not in the I-AT H group. During the first 5 min of the AT, the mean increase in CO2 was approximately 5 mmHg/min. Most patients in all groups met the AT criteria after 5 min of the test. CONCLUSIONS: The results from the study show that I-AT may compromise pulmonary function in some cases and is one of the reasons for the recommendation of a safer option, CPAP-AT, in the currently revised Polish BD criteria. During AT, the mean CO2 increase rate was 5 mmHg/min, which, in most patients, would allow the test to be completed after just 5 min.

Frailty is associated with an increased mortality among patients ≥ 80 years old treated in Polish ICUs

BACKGROUND: The increasing population of very old intensive care patients (VIPs) is a major challenge currently faced by clinicians and policymakers. Reliable indicators of VIPs' prognosis and purposefulness of their admission to the intensive care unit (ICU) are urgently needed. METHODS: This is a report from the Polish sample of the VIP1 multicentre cohort study (NCT03134807). Patients ≥ 80 years of age admitted to the ICU were included in the study. Information on the type and reason for admission, demographics, utilisation of ICU procedures, ICU length of stay, organ dysfunction and the decision to apply end-of-life care was collected. The primary objective was to investigate the impact of frailty syndrome on ICU and 30-day survival of VIPs. Frailty was assessed with the Clinical Frailty Scale (≥ 5 points on a scale of 1-9). RESULTS: We enrolled 272 participants with a median age of 84 (81-87) years. Frailty was diagnosed in 170 (62.5%) patients. The ICU and 30-day survival rates were equal to 54.6% and 47.3% respectively. Three variables were found to significantly increase the odds of death in the ICU in a multiple logistic regression model: SOFA score (OR = 1.16; 95%CI 1.16-1.24), acute mode of admission (OR = 5.1; 95%CI 1.67-15.57) and frailty (OR = 2.25; 95%CI 1.26-4.01). CONCLUSION: Measuring frailty in critically ill older adults can facilitate making more informed clinical decisions and help avoid futile interventions.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

Apnea testing using the oxygen insufflation method for diagnosis of brain death may compromise pulmonary function.

INTRODUCTION: The aim of our study was to compare the reliability and safety of the classical I-AT with the continuous positive airway pressure apnea test (CPAP-AT). MATERIAL AND METHODS: In the group of 48 patients (group O), an I-AT was performed at the end of BD diagnostic procedures, and approximately 1-1.5h later CPAP-AT with 100% FiO2 and CPAP of 10cm H2O, provided by ventilator in CPAP mode. After pre­oxygenation with 100% FiO2 for 10min, the PaO2/FiO2 ratio was recorded prior to I-AT at time-point one (T1) and prior to CPAP-AT at time-point two (T2). Group O was categorized into subgroup N-H (non-hypoxemic), consisting of 41 patients with good lung function, and subgroup H (hypoxemic) consisting of 7 patients with poor lung function. Within each subgroup PaO2/FiO2 at T1 and T2 were compared. RESULTS: In Group O, PaO2/FiO2 decreased from 321±128mmHg at T1 to 291±119mmHg at T2 (p=0.004). In subgroup N-H, PaO2/FiO2 declined from 355±103 to 321±100mmHg (p=0.008), and in subgroup H, PaO2/FiO2 remained almost unchanged. Additionally, in 4 patients from subgroup N-H, PaO2/FiO2 decreased below 200mmHg at T2. CONCLUSIONS: Our study indicates that I-AT may compromise pulmonary function and this may support the recommendation of safer CPAP-AT alternative.

Nonaccidental Out-of-Hospital Cardiac Arrest in an Urban Area as a Potential Source of Uncontrolled Organ Donors.

BACKGROUND Donation after cardiac death offers the possibility of increasing the pool of organs for transplantation by up to 30%. Maastricht category type 3 (M3) dominates in most countries with active DCD programs. During preparations to introduce a permanent program for uncontrolled donation after circulatory death in Szczecin, Poland, the donor pool has been estimated. In Poland, Maastricht category type 2 (M2) is considered a basic source for organ recovery. MATERIAL AND METHODS This was a retrospective cohort study of out-of-hospital cardiac arrests (OHCA) reported to local Emergency Medical Services (EMS) between 1 December 2014 and 30 November 2015. The following inclusion criteria were used in the analysis: demographic (age 18-60 years, known identity), clinical (no chest or abdominal injury, no cachexia as an equivalent of wasting diseases), and organizational (weekdays from 8:00 am to 3:00 pm). RESULTS During 12-month period, 118 EMS interventions were recorded in response to sudden cardiac arrest. The stratification process mentioned above used criteria to establish potential, eligible, qualified, and actual donor pools (27 (30.3%), 24 (26.4%), 7 (7.3%), and 6 (6.7%), respectively). To establish a "virtual" actual number of uDCD, the nationwide average level of lack of authorization for donation was 12%. CONCLUSIONS Activation of a permanent program of organ recovery from uDCD would increase the donor pool by 6 cases. Compared to the number of brain-dead donors referred from regional hospitals, this increase would be equivalent to the formation of a new reporting center. The number of transplantable organs could increase by 22% per year.

Evolution of apnoea test in brain death diagnostics.

The concept of brain death (BD) was initially described in 1959 and subsequently became widely accepted in the majority of countries. Nevertheless, the diagnostic guidelines for BD markedly differ, especially regarding the apnoea test (AT), a crucial element of clinical BD confirmation. The current basic guidelines recommend preoxygenation rather than disconnection from the ventilator and insertion of an oxygen insufflation catheter into the endotracheal tube. Although a properly prepared and conducted AT is relatively safe, it has to be aborted in cases of serious disturbances, such as severe cardiac arrhythmia, cardiac arrest, hypotension, hypercarbia, desaturation and tension pneumothorax. These complications may be more frequent in patients with previously existing risk factors, such as poor oxygenation, severe acidosis, hypotension and cardiac rhythm disturbances. Airway injuries can occur if the insufflation catheter is placed too deep or catheter-related obstruction of the intubation tube occurs. It is widely accepted that AT should be performed as the very last BD diagnostic procedure due to its possible lethal consequences. Reports concerning the possible pitfalls of AT and confounding situations have inspired attempts to determine the most effective and safe method of AT. The use of CPAP with oxygen supplementation is becoming highly popular. CPAP can be generated in three manners: directly by the ventilator; through the use of a CPAP valve with a reservoir; and through the use of a highly traditional T-piece system with a reservoir bag connected to distal tubing immersed in water.

Apnea test in the determination of brain death in patients treated with extracorporeal membrane oxygenation (ECMO).

Extracorporeal Membrane Oxygenation (ECMO) is a well-established method of support in patients with severe respiratory and/or circulatory failure. Unfortunately, this invasive method of treatment is associated with a high risk of neurological complications including brain death. Proper diagnosis of brain death is crucial for the termination of futile medical care. Currently, the legal system in Poland does not provide an accepted protocol for apnea tests for patients on ECMO support. Veno-arterial ECMO is particularly problematic in this regard because it provides both gas exchange and circulatory support. CO2 elimination by ECMO prevents hypercapnia, which is required to perform an apnea test. Several authors have described a safe apnea test procedure in patients on ECMO. Maximal reduction of the sweep gas flow to the oxygenator should maintain an acceptable haemoglobin oxygenation level and reduce elimination of carbon dioxide. Hypercapnia achieved via this method should allow an apnea test to be conducted in the typical manner. In the case of profound desaturation and an inadequate increase in the arterial CO2 concentration, the sweep gas flow rate may be increased to obtain the desired oxygenation level, and exogenous carbon dioxide may be added to achieve a target carbon dioxide level. Incorporation of an apnea test for ECMO patients is planned in the next edition of the Polish guidelines on the determination of brain death.

Original Protocol Using Computed Tomographic Angiography for Diagnosis of Brain Death: A Better Alternative to Standard Two-Phase Technique?

BACKGROUND The application of computed tomographic angiography (CTA) for the diagnosis of brain death (BD) is limited because of the low sensitivity of the commonly used two-phase method consisting of assessing arterial and venous opacification at the 60th second after contrast injection. The hypothesis was that a reduction in the scanning delay might increase the sensitivity of the test. Therefore, an original technique using CTA was introduced and compared with catheter angiography as a reference. MATERIAL AND METHODS In a prospective multicenter trial, 84 clinically brain-dead patients were examined using CTA and catheter angiography. The sensitivities of original CTA technique, involving an arterial assessment at the 25th second and a venous assessment at the 40th second, and the standard CTA, involving an arterial and venous assessment at the 60th second, were compared to catheter angiography. RESULTS Catheter angiography results were consistent with the clinical diagnosis of BD in all cases. In comparison to catheter angiography, the sensitivity of original CTA technique was 0.93 (95%CI, 0.85-0.97; p<0.001) and 0.57 (95%CI, 0.46-0.68; p<0.001) for the standard protocol. The differences were statistically significant (p=0.03 for original CTA and p<0.001 for standard CTA). Decompressive craniectomy predisposes to a false-negative CTA result with a relative risk of 3.29 (95% CI, 1.76-5.81; p<0.001). CONCLUSIONS Our original technique using CTA for the assessment of the cerebral arteries during the arterial phase and the deep cerebral veins with a delay of 15 seconds is a highly sensitive test for the diagnosis of BD. This method may be a better alternative to the commonly used technique.

Remifentanil for labour pain relief.

Labour is thought to be one of the most intense and painful experiences in a woman's life. Numerous studies using a Visual Analogue Scale invariably demonstrate that 20% of women in labour describe the pain as "unbearable" and 60% describe the pain as "very intense". Since the mid-1980s, continuous epidural analgesia during labour has been considered the gold standard of labour anaesthesia and is currently the most frequently used. There are situations in which this type of analgesia could not be used. An alternative pain management is administration of parenteral opioids, the most frequently used of which is pethidine. Its use is associated with adverse effects and unsatisfactory analgesia. Since the second half of the 20th century, a new generation of opioids, such as fentanyl or remifentanil, has been used. Despite their much better pharmacokinetic and pharmacodynamic parameters, obstetricians, midwives and neonatologists are most aware of pethidine, probably because it has been used for the longest period of time, despite its disadvantages and the risk that its use entails. The drug that is nearest to ideal is remifentanil. The countries in which it is widely used as an alternative type of labour anaesthesia have developed practice standards or guidelines practice. Guidelines and alternatives to pethidine protocols for effective labour analgesia in Poland might be merited.

CT Angiography in the Diagnosis of Brain Death.

Summary Brain death is defined as the irreversible cessation of functioning of the entire brain, including the brainstem. Brain death is principally established using clinical criteria including coma, absence of brainstem reflexes and loss of central drive to breathe assessed with apnea test. In situations in which clinical testing cannot be performed or when uncertainty exists about the reliability of its parts due to confounding conditions ancillary tests (i.a. imaging studies) may be useful. The objective of ancillary tests in the diagnosis of brain death is to demonstrate the absence of cerebral electrical activity (EEG and evoked potentials) or cerebral circulatory arrest. In clinical practice catheter cerebral angiography, perfusion scintigraphy, transcranial Doppler sonography, CT angiography and MR angiography are used. Other methods, like perfusion CT, xenon CT, MR spectroscopy, diffusion weighted MRI and functional MRI are being studied as potentially useful in the diagnosis of brain death. CT angiography has recently attracted attention as a promising alternative to catheter angiography - a reference test in the diagnosis of brain death. Since 1998 several major studies were published and national guidelines were introduced in several countries (e.g. in France, Austria, Switzerland, the Netherlands and Canada). This paper reviews technique, characteristic findings and criteria for the diagnosis of cerebral circulatory arrest in CT angiography.

Association of the rs10918594 of nitric oxide synthase 1 adaptor protein (NOS1AP) polymorphisms with the graft function after kidney transplantation.

BACKGROUND: The purpose of this study was to investigate the relationship of nitric oxide synthase 1 adaptor protein (NOS1AP) polymorphism with serum creatinine level and occurrence of delayed graft function (DGF) in kidney transplant recipients. MATERIAL/METHODS: This prospective observational study included 75 kidney transplantations. The data from 40 kidney donors (8 females, 32 males) included sex, age, and cause of death. Donors fully met multi-organ transplantation criteria. Recipient data included sex, age, cause of renal insufficiency, and time and number of hemodialyses prior to transplantation. Applying polymerase chain reaction restriction fragments length polymorphism method, we investigated rs10918594 NOS1AP polymorphism among the 75 kidney recipients. The function of every transplanted kidney was correlated with this polymorphism. We defined DGF as requirement for at least 1 hemodialysis after kidney transplantation. We investigated the association of NOS1AP polymorphism with the recipient serum creatinine levels at day 1 and 180 days after kidney transplantation and the occurrence of DGF. RESULTS: The analysis of variance showed higher serum creatinine levels in kidney recipients with GG genotype compared with the CC_CG genotype at day 1 and at day 180 post-transplantation. Occurrence of DGF in the post-operative period in kidney recipients with the variant genotypes CG compared with the GG_CC genotype was higher, although these differences were no statistically significant. CONCLUSIONS: Our data suggests no statistically significant association of the rs10918594 polymorphism of nitric oxide synthase 1 adaptor protein (NOS1AP) with the graft function after kidney transplantation.