LEADING ARTICLE
Tobacco smoking is the main modifiable risk factor for cardiovascular and respiratory diseases, cancer, premature disability and mortality. The article summarizes information about acute and chronic effects of tobacco smoking on the state of the kidneys in healthy people, as well as on the development and progression of chronic kidney disease. Various mechanisms of influence not only of nicotine, but also fine-dispersed components of tobacco smoke are considered. It discusses the development of nicotine dependence when using the main types of tobacco products, such as cigarettes, hookah tobacco, electronic cigarettes.
REVIEWS AND LECTURES
Introduction: Twenty years ago, the metabolism of vitamin K was connected with its role in hemostasis. Since that time has been shown that vitamin K exerts multiple functions mediated by the Gla-proteins, having as a cofactor vitamin K. Numerous publications affirm that these Gla-proteins are related to physiological processes beyond coagulations such as bone metabolism, vascular health and energy homeostasis. THE AIM: The aim of this research is to provide new data for vitamin K role in a myriad of physiological processes beyond blood clotting. Additionally, it aims to assess the potential new applications of vitamin K as a supplement for prevention bone and vascular disease.
Materials And Methods: Using the online databases Scopus, PubMed and Google Scholar a search with the keywords: «vitamin K2», «bone metabolism», «cardiovascular diseases», «osteocalcin» and «MGP» was conducted. Information regarding the effects of vitamin K on bone and vascular health was referred to in this work.
Results: Vitamin K and vitamin K-dependent-proteins play pivotal roles in the physiology of bone mineralization and in preventing ectopic calcification. Osteocalcin, a Gla protein located in bone and dentin, is important for bone mineralization. Following the posttranslational carboxylation of Glu-residues with a cofactor vitamin K2 (menaquinone), rather than vitamin K1 (phylloquinone), osteocalcin shows increased affinity for calcium. osteocalcin is believed to be involved in osteoblast regulation and hydroxyapatite crystal growth. Matrix GLa-protein (MGP), sharing some sequences with osteocalcin, is a local inhibitor of arterial calcification. Vitamin K deficiency impairs the function of osteocalcin and MGP and, therefore, presumably contributes to bone demineralization and vascular calcification, the so-called calcium paradox.
Conclusions: Vitamin K deficiencies, traditionally regarded as a cause for internal hemorrhages and blood clotting disorders, apparently can be linked to cardiovascular calcification and abnormal bone modelling. Appropriate treatment of vitamin K deficiency may improve bone and arterial health.In the majority of hemodialysis patients there are mineral and bone disorders, of which the most common is secondary hyperparathyroidism. A number of new products such as paricalcitol, cinacalcet and some phosphate-binding drugs have been developed and introduced in clinical practice in the past decade in order to correct this life-threatening complication of chronic kidney disease. A number of pharmacoeconomic studies have been carried out to determine the cost-effectiveness of appointing certain drugs due to increasing of the public expenditure in this therapy in many countries, including Russia. In this review, we consider a brief analysis of the methods for evaluating the profitability of medicines and the results of recent studies devoted to the evaluation of the cost-effectiveness of CKD-MBD treatment.
Hematopoietic cell transplantation (HCT) is becoming an increasing common treatment modality for a variety of diseases. Kidneys are recognized as a target organ of acute and chronic graft-versus host disease (GvHD).Glomerulopathy significantly limits patient life-time. Acute kidney injury occurs on average in 100 days after HCT in 15 – 73% of patients due to treatmentrelated toxity and radiation. Chronic GvHD is associated with chronic kidney disease. The majority of CKD after transplantation is idiopathic syndrome, thrombotic microangiopathy and nephrоtic syndrome.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
The aim: to investigate the glomerular filtration rate compared with the plasma level of bitter taste receptors TAS2R38 in asthma.
Patients and methods. 23 practically healthy persons and 52 patients with bronchial asthma were examined. The blood plasma TAS2R38 level was determined by an enzyme immunoassay. Glomerular filtration rate (eGFR) by CKD-EPI was estimated.
Results. There were significant differences in TAS2R38 receptor levels between men and women with allergic asthma, and in women these levels are the lowest. There was a significant decrease in eGFR in the non-allergic variant of asthma compared with the allergic variant of the disease, and only in women this decrease reaches a statistically significant value. When conducting a factor analysis, it was revealed that the level of bitter taste receptors TAS2R38 is associated with an estimated glomerular filtration rate with a high negative factor load.
The conclusion. A hypothesis is advanced on the possible regulatory (protective) function of plasma (soluble) TAS2R38 receptors in relation to the corresponding membrane receptors expressed on the cells of the kidney structures (glomeruli and tubules) in bronchial asthma in women.
The aim: to determine the clinical and diagnostic value of cystatin C, to evaluate estimated glomerular filtration rate (GFR) using creatinine and cystatin C concentration, to compare its results in patients with gout depending on the presence of arterial hypertension (AH).
Patients and methods. The study included 105 patients with gout. All patients underwent 24 hour ambulatory blood pressure monitoring (ABPM) using apparatus «BPLab» (Russia). Cystatin C was measured by enzyme immunoassay method. The glomerular filtration rate was calculated by CKD-EPI formulas based on creatinine, cystatin C, and creatinine with cystatin C concentrations.
Results. According to the obtained ABPM data, the main study group consisted of 75 men (71.4%) with AH, the comparison group included 30 (28.6%) patients showing no increase of blood pressure (BP). The concentration of cystatin C in patients with concomitant hypertension was 1.5 times higher than that in patients with normal blood pressure (p <0.05) and 2.1 times higher that in healthy men (p <0.001). In patients having gout with concomitant AH, the value of GFR calculated by the CKD-EPIcys and CKD-EPIcr-cys formulas was equally decreased. Patients having gout with normal blood pressure showed a significant decrease in GFR by the CKD-EPIcys method. The inverse correlation of GFR, calculated by the CKD-EPIcys formula with the serum uric acid level (r = -0.50, p <0.001), the content of CRP (r = -0.45, p <0.001), the average daily DBP (r = -0.43, p <0.001) and serum level of cystatin C (r = -0.51, p <0.001) was noted.
Conclusion. In patients with gout there is a significant increase in cystatin C level, which is more expressed with AH. The calculation of GFR based on cystatin C level concentrations reflects more severe stages of kidney injury. Thus cystatin C can be considered a new early marker of preclinical kidney injury in patients with gout.ORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATION
The aim: to evaluate the effect of the sodium-glucose cotransporter SGLT-2 inhibitor – empagliflozin on the kidney in nondiabetic Wistar rats with experimental heart failure (HF).
Material and methods. Chronic HF was induced by ligation the left coronary artery. Animals with HF in the first group (n=11) received empagliflozin (Jardiance®, Boehringer Ingelheim) orally (1 mg / kg/day) for 1 month. In the second group of rats with HF (n = 10) the drug is not administered. Concentrations and daily urinary excretion of glucose, protein and albumin were measured. The relative level of microRNA-21 urinary expression was established. Morphological examination of kidney tissue was performed using light microscopy.
Results. The administration of empagliflozin to experimental animals resulted in regularly higher values of diuresis, glucose concentration in urine and its daily excretion. There were no significant differences in levels of albuminuria and proteinuria or miRNA-21 expression in urine in groups with and without empagliflozin. The animals receiving the drug showed a slightly less pronounced damage to the cells of the tubular epithelium compared to rats with only heart failure.
Conclusion. The data obtained, at least confirm the renal safety of long-term empagliflozin administration even under conditions of high risk.Orozin (alpha-1 acid glycoprotein) pharmacological activity was studied on the experimental model of Kidney Ischemia-Reperfusion (K I/R). Actovegin was used as reference product.
The aim: to evaluate Orozin effects in kidney ischemia-reperfusion (K I/R) experimental model.
Matherial and methods: Male Wistar rats were carried out right-handed nephrectomy followed by mechanical clamping of the vascular bundle of the left kidney during 45 minutes and subsequent reperfusion. Drugs administrated intravemous in two steps: 10 minutes before stop mechanical clamping of the left kidney vascular bundle and 30 minutes after reperfusion. Blood chemistry value (creatinine and urea levels) were used as effectiveness criteria. After 2 and 24 hours of reperfusion the tissues of kidney were collected for histological assays.
Results: Study of experimental model of acute renal faiure showed cytoprotective effect of Orozin confirmed by biochemical and histological analysis.
The aim: to evaluate diagnostic and prognostic value of determination the concentration of homocysteine in children with congenital malformations (CM) of the urinary system (US) dependent of kidneys functional state.
Patients and methods. The study included 119 patients with US CM aged 3 to 18 years. A control group of 10 clinically healthy children. Patients divided into 3 groups: group I – 55 children with congenital vesicoureteral reflux (VUR), group II – 34 children with hydronephrosis and ureterohydronephrosis of congenital origin, group III – 30 children with other forms of US dysembryogenesis. Concentration of homocysteine in blood serum was assessed by ELISA.
Results. Hyperhomocysteinemia diagnosed in 60,9% of cases. Statistically significant differences with control group were revealed in the obstructive types where more often arterial hypertension (AH) and reduced glomerular filtration rate (GFR) were diagnosed. Significantly higher concentration of homocysteine are registered in patients with hypertension and reduced GFR.
Conclusion. The importance of estimating concentration of homocysteine in chronic kidney disease in patients with US CM was demonstrated.PROGRAM ON CONTINUOUS POSTGRADUATE EDUCATION ON NEPHROLOGY
Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare – but serious – side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.
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