The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL).

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein that is secreted mostly by immune cells such as neutrophils, macrophages, and dendritic cells. Its production is stimulated in response to inflammation. The concentrations of NGAL can be measured in plasma, urine, and biological fluids such as peritoneal effluent. NGAL is known mainly as a biomarker of acute kidney injury and is released after tubular damage and during renal regeneration processes. NGAL is also elevated in chronic kidney disease and dialysis patients. It may play a role as a predictor of the progression of renal function decreases with complications and mortality due to kidney failure. NGAL is also useful in the diagnostic processes of cardiovascular diseases. It is highly expressed in injured heart tissue and atherosclerostic plaque; its serum concentrations correlate with the severity of heart failure and coronary artery disease. NGAL increases inflammatory states and its levels rise in arterial hypertension, obesity, diabetes, and metabolic complications such as insulin resistance, and is also involved in carcinogenesis. In this review, we present the current knowledge on NGAL and its involvement in different pathologies, especially its role in renal and cardiovascular diseases.

Heart Metastases of Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a common genitourinary cancer. Of the several histologic types of RCC, clear cell renal cell carcinoma (ccRCC) is the most frequent. Due to the development of imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI), the incidence of ccRCC diagnosis has increased rapidly. However, up to one third of patients at prime diagnosis of ccRCC are at metastatic stadium of the disease. Metastases of ccRCC are found mostly in the lungs, bones and liver. Metastasis of ccRCC to the heart is an uncommon clinical situation. We present a rare case of metastatic stadium of ccRCC with metastases to heart tissue visualized in transthoracic echocardiography.

Resistin Contribution to Cardiovascular Risk in Chronic Kidney Disease Male Patients.

BACKGROUND: Resistin is a molecule that belongs to the Resistin-Like Molecules family (RELMs), the group of proteins taking part in inflammatory processes. Increased resistin concentrations are observed in cardiovascular complications. Resistin contributes to the onset of atherosclerosis and intensifies the atherosclerotic processes. The aim of this study was to investigate the relationship between resistin and cardiovascular (CV) risk in men with chronic kidney disease (CKD) not treated with dialysis. MATERIALS AND METHODS: One hundred and forty-two men were included in the study: 99 men with eGFR lower than 60 mL/min/1.73 m2 and 43 men with eGFR ≥ 60 mL/min/1.73 m2. CV risk was assessed. Serum resistin, tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured among other biochemical parameters. RESULTS: We observed that resistin concentrations were significantly higher in patients with CKD compared to individuals with eGFR ≥ 60 mL/min/1.73 m2 (p = 0.003). In CKD, after estimating the general linear model (GLM), we found that resistin is associated with CV risk (p = 0.026) and PAI-1 serum concentrations (0.012). The relationship of PAI-1 with resistin depends on the level of CV risk in CKD (p = 0.048). CONCLUSIONS: Resistin concentrations rise with the increase of CV risk in CKD patients and thus resistin may contribute to the progression of cardiovascular risk in this group of patients. The relationship between resistin and CV risk is modified by PAI-1 concentrations.

Melatonin Treatment in Kidney Diseases.

Melatonin is a neurohormone that is mainly secreted by the pineal gland. It coordinates the work of the superior biological clock and consequently affects many processes in the human body. Disorders of the waking and sleeping period result in nervous system imbalance and generate metabolic and endocrine derangements. The purpose of this review is to provide information regarding the potential benefits of melatonin use, particularly in kidney diseases. The impact on the cardiovascular system, diabetes, and homeostasis causes melatonin to be indirectly connected to kidney function and quality of life in people with chronic kidney disease. Moreover, there are numerous reports showing that melatonin plays a role as an antioxidant, free radical scavenger, and cytoprotective agent. This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress occur, regardless of the mechanism. The administration of melatonin has a renoprotective effect and inhibits the progression of complications connected to renal failure. It is very important that exogenous melatonin supplementation is well tolerated and that the number of side effects caused by this type of treatment is low.

Changes of Hemodynamic Parameters after Intradialytic Glucose Injection.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis (HD). Current methods of IDH prevention are insufficient. METHODS: We analyzed the intradialytic time course of systolic (SBP), diastolic (DBP), mean arterial (MAP), pulse pressure (PP), and heart rate (HR) in a group of chronic kidney disease (CKD) patients. First, 30 min into HD, a 40% glucose solution was injected into the venous line of the extracorporeal circulation at a dose of 0.5 g/kg of dry weight. Pressures and HR were measured in frequent intervals. Relative volume overload was determined by bioimpedance spectroscopy. RESULTS: Thirty-five participants were studied. SBP increased after 5, 10, and 20 min of glucose infusion. DBP increased after 2 and 3 h and also at the end of HD. PP increased after 5, 10, and 20 min of glucose infusion and fell after the 2nd and 3rd hour and also at the end of HD. MAP increased after 2 and 3 h of glucose injection and at the end of HD. Significant interactions of the time course of SBP, DBP, MAP, with HR at baseline and of the time course of PP with fluid overload were observed. Symptomatic hypotensive episodes were absent. CONCLUSIONS: Glucose infusions during HD prevent symptomatic IDH and do not cause severe hypertensive episodes.

Cardiovascular Response to Intravenous Glucose Injection during Hemodialysis with Assessment of Entropy Alterations.

BACKGROUND: The quality of autonomic blood pressure (BP) control can be assessed by the entropy of serial BP data. The aim of this study was to evaluate the effect of hemodialysis (HD) and glucose infusion (GI) on amplitude aware permutation entropy (AAPE) of hemodynamic variables during HD in chronic kidney disease patients with and without type-2 diabetes mellitus (DM). METHODS: Twenty-one patients without DM (NDO) and ten with DM were studied. Thirty minutes after the start of HD, a 40% glucose solution was administered. Hemodynamic data were extracted from continuous recordings using the Portapres® system. RESULTS: AAPE decreased during HD in all patients and all hemodynamic signals with the exception of AAPE of mean and diastolic BP in DM patients. GI led to an increase in AAPE for cardiac output in all patients, while AAPE for heart rate and ejection time increased only in DM studies, and AAPE for systolic, diastolic, and mean arterial pressure, as well as total peripheral resistance, increased only in NDO patients. CONCLUSIONS: The reduction in entropy during HD indicates impaired autonomic control in response to external perturbations. This state is partially reversed by the infusion of glucose with differences in central and peripheral responsiveness in DM and NDO patients.

Left Ventricular Diastolic Dysfunction in Chronic Kidney Disease Patients Not Treated with Dialysis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is observed in the early stages of chronic kidney disease (CKD) and may lead to heart failure with preserved ejection fraction (HFpEF). The purpose of our study was to investigate the association between metabolic, nutritional and inflammatory parameters and LVDD in CKD and non-CKD patients. METHODS: Two groups of patients were recruited to the study: 93 men with CKD and eGFR lower than 60 mL/min/1.73 m2 and 40 men without kidney function decrease with eGFR ≥ 60 mL/min/1.73 m2. Transthoracic echocardiography was performed to evaluate the diastolic function of the left ventricle. Bioimpedance spectroscopy (BIS) was used to measure overhydration and lean body mass. We also measured the serum concentrations of albumin, glucose, haemoglobin A1c (HgbA1c), fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and osteoprotegerin (OPG). RESULTS: We observed that elevated serum fibrinogen and glucose concentrations were associated with LVDD independently of CKD status. Serum fibrinogen concentrations increased with the advancement of LVDD. Low albumin concentrations in CKD were related with LVDD. In the control group, lower muscle mass presented as lean tissue index (LTI) and lean tissue mass (LTM), and overhydration were associated with LVDD. In the group of patients without kidney function decrease the OPG concentrations were significantly higher in those with LVDD, and they rose with the advancement of LVDD. CONCLUSIONS: Elevated inflammatory parameters, increased serum glucose concentrations and worse nutritional status are the states that may impair the diastolic function of the left ventricle in CKD and non-CKD patients. Serum OPG levels are elevated in patients without kidney function decrease and LVDD and its concentrations rise with the advancement of LVDD.

Testosterone Deficiency as One of the Major Endocrine Disorders in Chronic Kidney Disease.

Reduced testosterone concentration is nowadays thought to be one of the main endocrine disorders in chronic kidney disease (CKD). It is caused by the dysfunction of the hypothalamic-pituitary-gonadal axis. The role of testosterone is multifactorial. Testosterone is responsible not only for reproductive processes, but it is a hormone which increases bone and muscle mass, improves lipid profile, insulin sensitivity, erythropoiesis, reduces blood pressure, and ameliorates mood and perception. The implications of hypogonadism in CKD are infertility and loss of libido, reduction of muscle mass and strength, disorders in bone mineralization, the development of sarcopenia and protein energy wasting (PEW), progression of atherosclerosis, increased visceral adiposity, insulin resistance, and anaemia. Reduced testosterone serum concentrations in CKD are associated with increased mortality rate. Testosterone supplementation improves sexual functions, reduces the level of inflammatory markers and blood pressure, stimulates muscle protein synthesis, improves insulin sensitivity and lipid profile, and increases muscle mass, bone mineral density, and haemoglobin concentration. It positively affects mood and well-being. The modes of testosterone supplementation are intramuscular injections, subcutaneous pellets, and percutaneous methods-patches and gels. Successful kidney transplantation may improve gonadal function and testosterone production, however, half of men with low testosterone concentrations before kidney transplantation do not restore hormonal function.

Serum Osteoprotegerin Is an Independent Marker of Left Ventricular Hypertrophy, Systolic and Diastolic Dysfunction of the Left Ventricle and the Presence of Pericardial Fluid in Chronic Kidney Disease Patients.

BACKGROUND: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. METHODS: One hundred and one men with CKD stage 3-5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. RESULTS: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). CONCLUSIONS: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients.

Relationships between Sclerostin, Leptin and Metabolic Parameters in Non-Dialysis Chronic Kidney Disease Males.

Sclerostin is an inhibitor of the Wnt-beta-catenin pathway. The relationship between sclerostin and adipose tissue or between sclerostin and nutritional status has been the subject of research interest in the last decade. Sclerostin concentrations are elevated in patients with chronic kidney disease (CKD). Leptin is an adipocytokine which inhibits food intake by stimulating the satiety center in the hypothalamus. Leptin concentrations rise with the reduction of eGFR (glomerular filtration rate). The aim of this study was to investigate the possible association between sclerostin and leptin, between sclerostin and selected poor prognostic factors of CKD progression, and between sclerostin and nutritional parameters in non-dialysis CKD male patients. 101 men with non-dialysis CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure body composition. Blood samples were drawn to measure the serum concentrations of sclerostin, leptin, creatinine, hemoglobin (Hgb), parathormone (PTH), inflammatory markers, and markers of nutritional status. We also measured homeostatic model assessment of insulin resistance (HOMA-IR) as well as blood pressure. We observed a significant, positive relationship between sclerostin and age, leptin, and glycated hemoglobin (HgbA1c) concentrations. A significant, negative association was observed between sclerostin and eGFR. Sclerostin is associated with leptin in non-dialysis CKD male patients. Sclerostin is also related to metabolic disturbances such as hyperglycemia in this population.

Serum Osteoprotegerin Is an Independent Marker of Metabolic Complications in Non-DialysisDependent Chronic Kidney Disease Patients.

BACKGROUND: Osteoprotegerin (OPG) belongs to the tumour necrosis factor superfamily and is known to accelerate endothelial dysfunction and vascular calcification. OPG concentrations are elevated in patients with chronic kidney disease. The aim of this study was to investigate the association between OPG levels and frequent complications of chronic kidney disease (CKD) such as anaemia, protein energy wasting (PEW), inflammation, overhydration, hyperglycaemia and hypertension. METHODS: One hundred non-dialysis-dependent men with CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure overhydration, fat amount and lean body mass. We also measured the serum concentrations of haemoglobin, albumin, total cholesterol, C-reactive protein (CRP), fibrinogen and glycated haemoglobin (HgbA1c), as well as blood pressure. RESULTS: We observed a significant, positive correlation between OPG and age, serum creatinine, CRP, fibrinogen, HgbA1c concentrations, systolic blood pressure and overhydration. Negative correlations were observed between OPG and glomerular filtration rate (eGFR), serum albumin concentrations and serum haemoglobin level. Logistic regression models revealed that OPG is an independent marker of metabolic complications such as anaemia, PEW, inflammation and poor renal prognosis (including overhydration, uncontrolled diabetes and hypertension) in the studied population. CONCLUSION: Our results suggest that OPG can be an independent marker of PEW, inflammation and vascular metabolic disturbances in patients with chronic kidney disease.