[Teaching Evidence Based Medicine EBM in medical faculties in Poland]. / Nauczanie Evidence Based Medicine (EBM) na wydzialach lekarskich w Polsce.

Evidence Based Medicine (EBM) is a core competence for clinicians and should be taught in all medical faculties. AIM: The aim of the study was to survey how EBM is taught in medical faculties in Poland. MATERIALS AND METHODS: We conducted a questionnaire study, asking the deans of medical faculties to fill it. RESULTS: We got a response from all medical faculties. Teaching of EBM is carried out in all medical faculties in Poland, apart from Kopernicus University in Torun. EBM is a separate subject in 7 faculties (from 5 to 36 hours). The most often EBM is taught on the IIIrd to the Vth course of the study with exception of Kielce, where it is held on the IInd course. In the most faculties teaching EBM is obligatory. In Lodz and Krakow, apart of being obligatory, EBM may be continued facultatively. Teachers are competent in EBM and continuosly trained. EBM study ends with a credit in 3 faculties. Some faculties intend to introduce EBM as a separate subject or extend number of hours. CONCLUSIONS: Our study showed that EBM is generally taught in medical faculties in Poland although in various length (5-36 hours). It should be extended to 30 hours and unified within a separate subject which ends with a credit.

Syphilis in Poland is on the rise and underreported.

INTRODUCTION: Despite the availability of diagnostic tests and effective treatment, there has been a problem with vigilance and reporting of that infectious disease in many countries including Poland. AIM: To compare the incidence of syphilis in Poland in years 2010-2016 according to the mandatory epidemiological surveillance system with the data of the National Health Fund (NHF). MATERIAL AND METHODS: Data of the NHF in Poland were collected. The total number of patients with syphilis (all forms) was estimated on the basis of their unique identifying numbers (PESEL). RESULTS: The steady increase in the incidence of syphilis in Poland throughout 2010-2016 was found, apart from the congenital form of the disease, which decreased since 2010. The higher prevalence of syphilis was noted in men. The number of hospitalized patients remained constant. According to the data of the NHF, the number of cases of syphilis in Poland was twofold higher as compared to the statistics of the mandatory epidemiological surveillance system (National Institute of Public Health - National Institute of Hygiene, NIPH-NIH), which was the basis of reports published up to date. CONCLUSIONS: Our work shows that there is a remarkable underreporting of syphilis in the mandatory epidemiological surveillance system in Poland, involving also hospitalized patients. The use of the data of NHF in the surveillance of syphilis in Poland is proposed.

Indoxyl sulfate - the uremic toxin linking hemostatic system disturbances with the prevalence of cardiovascular disease in patients with chronic kidney disease.

BACKGROUND: During chronic kidney disease progression, kidney-specific risk factors for cardiovascular disease come into play. The present study investigated the impact of indoxyl sulfate, dietary tryptophan-derived uremic toxin, accumulated in the blood of patients with chronic kidney disease on hemostatic parameters, markers of inflammation, oxidative stress and monocyte to macrophage transition. METHODS: Fifty-one CKD patients not undergoing hemodialysis were enrolled in the study. Coagulation factors, fibrinolytic parameters, adhesion molecules, endothelial dysfunction markers, oxidative stress as well as inflammation markers were examined using immune-enzymatic method. Indoxyl sulfate levels were assessed using high-performance liquid chromatography. Biochemical parameters were determined by routine laboratory techniques using an automated analyzers. All assessed parameters were compared with controls and subjected to cross-sectional statistical analysis. RESULTS: Elevated concentrations of indoxyl sulfate, the vast majority of parameters affecting hemostasis, and markers of renal insufficiency conditions were observed. Part of hemostatic factors, namely tissue factor, von Willebrand factor, thrombomodulin, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion protein were correlated with the fraction of indoxyl sulfate. A significant quantity of assessed parameters showed strong correlations with superoxide-dismutase, renal insufficiency rate, C-reactive protein, and neopterin. Levels of indoxyl sulfate were independently associated with markers of impaired endothelial function (thrombomodulin, adhesion molecules), oxidative stress (superoxide-dismutase) and monocytes activation determinant (neopterin), which indicate unconventional links between these systems and the role of indoxyl sulfate. Furthermore, parameters that correlated with the levels of indoxyl sulfate (von Willebrand factor, soluble urokinase-type plasminogen activator receptor, soluble intercellular adhesion molecule-1) were positively associated with the prevalence of cardiovascular disease in a CKD patients. CONCLUSIONS: The study demonstrated that in conditions of chronic exposure to uremic toxins, indoxyl sulfate seems to be one of the "missing links" between impaired renal function and prevalence of cardiovascular events, especially hemostatic disorders. The main functions of the action appear to be altered monocytes activation, intensified inflammatory process, and augmented oxidative stress by this uremic toxin.

YKL-40 in hemodialyzed patients with and without cardiovascular complications - the enhancement by the coexistence of the seropositivity against hepatitis C virus infection.

BACKGROUND: YKL-40 is a new biomarker of inflammation, which is expressed by several cell types of the immune system. The aim of the present study was to evaluate plasma YKL-40 levels in hemodialysis (HD) patients and to establish its potential role as a new inflammatory biomarker of cardiovascular disease (CVD) in this population. METHODS: YKL-40 and two other inflammatory markers: high sensitivity C-reactive protein (hsCRP) and neopterin levels were measured in 70 HD patients both with and without CVD and in 38 healthy controls. RESULTS: Median YKL-40, hsCRP and neopterin levels were significantly elevated in HD patients, particularly those with CVD, compared to controls. YKL-40 was no associated with hsCRP, but it is strongly and independently associated with plasma neopterin levels in HD patients. The coexistence of the seropositivity against hepatitis C virus (anti-HCV) infection increased both YKL-40 and neopterin levels in these patients. This effect was particularly seen in subjects with CVD. Moreover, high neopterin levels were exclusively associated with anti-HCV seropositivity, whereas hsCRP values were only associated with the presence of CVD. CONCLUSIONS: This study indicated for the first time that plasma YKL-40 level is increased in HD patients, especially in those with CVD, and it is independently associated with neopterin - an biomarker of monocyte/macrophage activation. There was no association between YKL-40 and hsCRP, the common indicator of an inflammatory state. Moreover, the coexistence of anti-HCV seropositivity had an important impact on plasma YKL-40 levels in HD patients particularly those with cardiovascular complications.

Antibodies against Nε-homocysteinylated proteins in patients on different methods of renal replacement therapy.

BACKGROUND: High levels of antibodies against Nε-homocysteinylated (Nε-Hcy) proteins have been observed in patients on long-term hemodialysis (HD). We sought to investigate whether these antibodies are present in patients on peritoneal dialysis (PD) in comparable titers and to characterize the factors that determine levels of those antibodies in both patient groups. METHODS: The study involved 80 patients on HD and age- and sex-matched 75 subjects on PD. Serum IgG antibodies against Nε-Hcy-albumin and -hemoglobin were determined using in-house enzyme-linked immunosorbent assays. Total homocysteine (tHcy), folate, 8-isoprostaglandin F2α (8-iso-PGF2α) and paraoxonase-1 (PON-1) activity were also measured. RESULTS: Patients on PD and those on HD had similar levels of anti-Nε-Hcy-albumin [absorbancy at 490 nm: 0.571 (0.519-0.609) vs. 0.583 (0.523-0.625), p=0.41, respectively] and anti-Nε-Hcy-hemoglobin antibodies [0.659 (0.597-0.705) vs. 0.664 (0.597-0.722), p=0.60, respectively]. In both groups levels of the antibodies correlated with tHcy (r from 0.54 to 0.77, p<0.0001), 8-iso-PGF2α (r from 0.57 to 0.77, p<0.0001), and folate (r from -0.59 to -0.74, p<0.0001) levels, but not with the cause of renal disease, dialysis vintage, a history of coronary artery disease or PON-1 activity. In the multivariate logistic regression, after adjustment for potential confounders, plasma tHcy was the independent predictor of antibodies against Nε-Hcy-proteins irrespective of the method of dialysis. CONCLUSIONS: Levels of antibodies against Nε-Hcy-proteins are similar in patients on long-term PD and HD. The level of tHcy is the only independent predictor of both antibodies irrespective of the dialysis method.

GDF15 is related to anemia and hepcidin in kidney allograft recipients.

UNLABELLED: Anemia is more prevalent in renal transplant recipients than in GFR-matched chronic kidney disease patients. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia or inflammation. Growth differentiation factor 15 (GDF15) was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. The aim of the study was to assess GDF15 levels with relation to iron parameters in 62 stable kidney allograft recipients maintained on triple immunosuppressive therapy. METHODS: Complete blood count, urea, creatinine, and iron status were assessed by standard methods. We measured GDF15, hepcidin, hemojuvelin, IL-6 and NGAL with commercially available assays. RESULTS: Mean levels of GDF15, NGAL, hepcidin and hemojuvelin were significantly higher in kidney allograft recipients when compared to the control group (p < 0.001 for all). GDF15 was significantly higher in patients with anemia according to the WHO definition when compared to their nonanemic counterparts (p < 0.05). GDF15 levels were not dependent on the type of immunosuppressive therapy. In univariate analysis GDF15 was related to kidney function (creatinine r = 0.39, p < 0.01, eGFR by MDRD r = -0.37, p < 0.01), urea (r = 0.39, p < 0.01), uric acid (r = 0.42, p < 0.01), hepcidin (r = -0.32, p < 0.01), IL-6 (r = 0.28, p < 0.05), hemoglobin (r = -0.32, p < 0.05), and NGAL (r = -0.35, p < 0.01). GDF15 was not related to serum iron, or ferritin. In multivariate analysis, hepcidin was found to be a predictor of GDF15. In conclusion, our preliminary data may suggest possible mutual relations between GDF15 and hepcidin in patients with kidney disease and that GDF15 might be involved in the pathogenesis of anemia in kidney allograft recipients. However, the role of inflammation should be also elucidated.

Circulating levels of renalase, norepinephrine, and dopamine in dialysis patients.

BACKGROUND: hRenalase may degrade catecholamines and regulate sympathetic tone and blood pressure (BP). The aim of the study was to assess dopamine (DA), norepinephrine (NE), and renalase in 75 hemodialysis (HD) and 26 peritoneal dialysis (PD) patients and their correlations with heart rate (HR), BP, a type of hypotensive therapy, and residual renal function. METHODS: Renalase, DA, NE were studied using commercially available assays. RESULTS: Renalase and NE were higher and DA was lower in dialyzed groups comparing to healthy volunteers. Hemodialysis patients had lower NE and higher renalase level. Norepinephrine was higher in anuric patients in HD group. Renalase correlated with dialysis vintage and inversely with residual diuresis. Dopamine correlated with residual diuresis in the whole study cohort, with HR in PD patients, with renalase in HD patients. Norepinephrine correlated with aortic diameter in PD patients. Norepinephrine was significantly higher in patients with coronary artery disease (CAD) in HD group. Hemodialysis population with CAD had lower NE and higher DA and renalase level than their PD counterparts. In the follow up, 27% of HD group died. Cardiac death was diagnosed in 17% and there was higher renalase level than in noncardiac death. CONCLUSIONS: Elevated level of circulating renalase in dialysis patients is rather related to kidney function and the sympathetic nervous system hyperactivity found in this population. The real excess of renalase in the pathogenesis of cardiovascular disorders in patients with chronic kidney disease still remains to be proven. If confirmed, it may give a new way for pathophysiological therapy.

VAP-1 in peritoneally dialyzed patients.

VAP-1 (vascular adhesion protein-1) possesses semicarbazide-sensitive amine oxidase (SSAO) activity. It has also been found that serum VAP-1 was elevated in acute and chronic hyperglycemia and in patients with diabetes as well as in chronic kidney disease. Renalase, with possible monoamine oxidase activity, which breaks down catecholamines such as SSAO, is expressed in the endothelium as well as in the kidney. The aim of the study was to assess serum VAP-1 levels in peritoneally dialyzed (PD) patients and factors explaining its variability. This pilot study was performed on 25 peritoneally dialyzed patients, including 4 patients with type 2 diabetes. We found that the mean VAP-1 was significantly higher in chronic ambulatory peritoneal dialysis (CAPD) patients when compared to the control group (p<0.05). Dopamine was significantly lower in PD patients when compared to the healthy volunteers (p<0.05), whereas noradrenaline was significantly higher in PD patients relative to the healthy volunteers (p<0.01). There was a significant difference in the VAP-1 concentration in the group with and without residual renal function (p<0.05) as well as between 10 patients with hyperglycemia when compared to patients with normoglycemia (p<0.05). There was no effect of gender on the serum VAP-1 levels. In PD patients VAP-1 correlated with systolic blood pressure (r=-0.4, p<005), residual renal function (r=-0.62, p<0.05), and glucose (=0.54, p<0.05). We concluded that VAP-1, elevated in patients on PD, was predominantly dependent on residual kidney function and glucose level, factors both linked to endothelial damage and cardiovascular complications.

VAP-1, a novel molecule linked to endothelial damage and kidney function in kidney allograft recipients.

BACKGROUND/AIMS: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semicarbazide sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, endothelial cells with functional monoamine oxidase activity. The oxidation process generates harmful products that may be involved in atherosclerosis and vascular damage. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus and obesity. On the other hand, renalase, with possible monoamine oxidase activity, which breaks down catecholamines like SSAO, is also expressed in the endothelium as well as in the kidney. The aim of the study was to assess VAP-1 levels and its correlations with endothelial injury markers and renalase in 50 kidney allograft recipients. METHODS: Hemoglobin, urea, creatinine, rate were studied by standard laboratory method in the hospital central laboratory. We assessed markers of endothelial function/injury: vWF, thrombomodulin, ICAM, VCAM, CD40L, CD44, CD146, inflammation: hsCRP, and IL-6 and adipocytokines: leptin, adiponectin, visfatin, apelin with commercially available assays. RESULTS: The mean serum VAP-1 in Tx was significantly higher comparing to the control group. In kidney transplant recipients VAP-1 correlated with BMI (r=0.39, p<0.01), CD44 (r=0.27, p<0.05), hsCRP (r=0.28, p<0.05), serum creatinine (r=0.29, p<0.05), eGFR (CKD-EPI formula r=-0.27, p<0.05, MDRD r=-0.27,p<0.05, Cockcroft-Gault r=-0.35,p<0.01), serum urea (r=0.27, p<0.05), CD146 (r=0.49, p<0.001), CD40L (r=0.26, p<0.06), and renalase (r=0.34, p<0.05). In multiple regression analysis VAP-1 was predicted 80% by serum creatinine (beta value 0.33, p=0.01), and CD146 (beta value 43, p=0.0005). CONCLUSION: VAP-1, elevated in kidney transplant recipients, is predominantly dependent on endothelial damage and kidney function, which deteriorated with time after kidney transplantation.

Renalase, a novel enzyme involved in blood pressure regulation, is related to kidney function but not to blood pressure in hemodialysis patients.

UNLABELLED: Renalase, secreted by the kidney, degrades catecholamines and may play a role in the regulation of sympathetic tone and blood pressure. The aim of this study was to assess serum renalase levels in hemodialysis patients and their relationship to blood pressure control, type of antihypertensive therapy and the presence of residual renal function. RESULTS: The mean serum renalase in the study cohort was significantly higher than in the control group (27.53 ± 7.18 vs. 3.86 ± 0.73 µg/ml, p < 0.001). The serum renalase concentration was significantly lower in patients with residual renal function when compared to the anuric patients. The type of hypotensive treatment (ß-blockers, ACE inhibitors or AT1 receptor blockers) did not affect renalase levels. There was a significant inverse correlation between the serum renalase and age (r = -0.28, p = 0.023) and residual renal function (r = -0.327, p = 0.001). Renalase was not related to blood pressure, heart rate or hemodialysis vintage. CONCLUSION: Elevated renalase levels in HD patients may be due to impaired kidney function. Further studies are needed to prove or disprove the possible role of renalase in the pathogenesis of hypertension in patients with kidney diseases.

The mechanism of vascular calcification - a systematic review.

Calcification of vessels reduces their elasticity, affecting hemodynamic parameters of the cardiovascular system. The development of arterial hypertension, cardiac hypertrophy, ischemic heart disease or peripheral arterial disease significantly increases mortality in patients over 60 years of age. Stage of advancement and the extent of accumulation of calcium deposits in vessel walls are key risk factors of ischemic events. Vascular calcification is an active and complex process that involves numerous mechanisms responsible for calcium depositions in arterial walls. They lead to increase in arterial stiffness and in pulse wave velocity, which in turn increases cardiovascular disease morbidity and mortality. In-depth study and thorough understanding of vascular calcification mechanisms may be crucial for establishing an effective vasculoprotective therapy. The aim of this study was to present a comprehensive survey of current state-of-the-art research into the impact of metabolic and hormonal disorders on development of vascular calcification. Due to strong resemblance to the processes occurring in bone tissue, drugs used for osteoporosis treatment (calcitriol, estradiol, bisphosphonates) may interfere with the processes occurring in the vessel wall. On the other hand, drugs used to treat cardiovascular problems (statins, angiotensin convertase inhibitors, warfarin, heparins) may have an effect on bone tissue metabolism. Efforts to optimally control calcium and phosphate concentrations are also beneficial for patients with end-stage renal disease, for whom vessel calcification remains a major problem.

Hepatocyte growth factor in saliva of patients with renal failure and periodontal disease.

BACKGROUND: Hepatocyte growth factor (HGF), endogenous cytokine with pleiotropic repairing and regeneration properties in relation to most tissues and organs, contributes to the progression of periodontal disease (PD). Furthermore, PD is a significant health problem in patients with chronic renal failure (CRF). The role of HGF in the development of PD in this specific population was not a subject of research so far. MATERIAL AND METHODS: The following groups were enrolled in the study: (1) 26 chronic hemodialysis (HD) subjects, (2) 26 patients treated by continuous ambulatory peritoneal dialysis (CAPD), (3) 28 predialysis CRF patients, (4) 26 subjects with advanced PD (without coexisting diseases), and (5) 20 healthy subjects without PDs. HGF level in saliva was measured using the immunoenzymatic method. Gingival index, papillary bleeding index, plaque index, and the loss of clinical attachment level were evaluated. RESULTS: The HGF level in saliva of HD patients was twice higher than in that of subjects with healthy periodontium. Direct relationships between proper HGF level in saliva and the indices GI, PBI, and PI in CAPD-treated patients and with more severe PD were shown. It was found that PD is most advanced in HD patients, moderately in CAPD-treated patients and to the smallest extent in predialysis CRF patients. CONCLUSIONS: The HGF level in mixed saliva is the index of PD progression in subjects without renal failure and in CAPD-treated patients. PD is common in renal failure patients and is a significant problem concerning general health status.

Renalase, stroke, and hypertension in hemodialyzed patients.

INTRODUCTION: Hypertension and kidney disease have been associated with increased incidence of stroke. Renalase, a newly discovered hormone, is secreted by the kidney and circulates in blood. The aim of this study was to assess possible correlations between renalase, blood pressure, stroke, and cardiovascular status in prevalent hemodialyzed patients. METHODS: Renalase was assessed using commercially available assay. Echocardiography was performed in each patient. RESULTS: Serum renalase was significantly lower in patients with a history of stroke (21%) than in patients without it. Similarly, renalase was significantly lower in hypertensive patients (82%) when compared with normotensives. Serum renalase correlated with creatinine, residual renal function, and transferrin saturation. The only predictor of renalase in multiple regression analysis was the presence of hypertension explaining 90% of the renalase variations. CONCLUSIONS: Our preliminary results suggest that renalase, probably due to the sympathetic nervous system hyperactivity, could be associated with hypertension and cardiovascular complications, including stroke in hemodialyzed patients. However, further studies are needed to establish the possible role of renalase in these complications. Renalase is "a new postulated therapeutic target."

Impact of diabetes mellitus on survival in patients with end-stage renal disease: a three-year follow-up.

BACKGROUND/AIMS: To assess the impact of diabetes mellitus (DM) on clinical outcome in patients with end-stage renal disease (ESRD) on a 3-year follow-up. METHODS: 58 ESRD patients were divided into 2 groups according to the presence of DM. We analyzed following end points: death, cardiac arrest, myocardial infarction, stroke, hospitalizations due to cardiovascular causes, revascularization, and combined end point. RESULTS: Among diabetics, 14 (77.8%) had significant atherosclerotic changes, in the group without DM only 8 (38.1%), p = 0.01. In the group without DM, 14 (46.7%) patients reached combined end point, while in the group with DM 16 (53.3%) patients, p = 0.0013. There were no statistical differences in mortality (p = 0.423). CONCLUSION: Survival of hemodialyzed diabetic patients is not inferior to nondiabetics; however, morbidity is significantly higher due to adverse cardiac events.

Lack of effect of the CD14 promoter gene C-159T polymorphism on nutritional status parameters in hemodialysis patients.

BACKGROUND: CD14 is a membrane glycoprotein that acts as a co-receptor for the detection of bacterial lipopolysaccharide (LPS). Mutual interaction between CD14 and LPS plays an important role in the innate immune system. Increased serum soluble CD14 levels have been described in hemodialysis (HD) patients, and linked to increased mortality risk, inflammation and protein-energy wasting. The expression of CD14 may be influenced by CD14 promoter gene C-159T polymorphism. This study aimed to clarify the possible association between CD14 promoter gene C-159T polymorphism and nutritional status in hemodialysis patients. MATERIAL/METHODS: The study population consisted of 185 (104 males; 81 females) long-term HD patients treated in 5 dialysis centers. The control group consisted of 112 apparently healthy volunteers (32 males and 80 females). Nutritional status was assessed using a modified SGA scale, and anthropometric methods (BMI, WHR, waist, hip and mid-arm circumferences, biceps, triceps, subocular and subscapular skinfolds). Biochemical parameters evaluated included: CRP, albumin, creatinine, urea, cholesterol, triglycerides and TIBC. CD14 promoter gene C-159T polymorphism was determined by restriction fragment length polymorphism, after digestion of the PCR product with Hae III restriction endonuclease. RESULTS: Genotype and allele frequencies were similar to controls and compliant with Hardy-Weinberg equilibrium. No between-group differences were detected in measured variables with the exception of lower triglyceride levels in carriers of C allele in comparison to TT genotype. CONCLUSIONS: CD14 promoter gene C-159T polymorphism does not seem to be associated with nutritional status parameters in HD patients. It does seem, however, to influence triglyceride blood levels.

Copeptin and its relation to arteriovenous fistula (AVF) type and NYHA class in hemodialysis patients.

Copeptin is cosynthesized with vasopressin, also known as anti-diuretic hormone, with similar plasma levels. In the past 2 years, copeptin has been studied as a diagnostic and prognostic marker in infections and other diseases. In patients with decompensated heart failure, copeptin was an accurate prognostic marker for mortality. Cardiovascular disease is a major contributor to the mortality and morbidity in chronic kidney disease. Creation of an arteriovenous fistula (AVF) might contribute to the development or worsening of congestive heart failure (CHF). The aim of the study was to assess associations between copeptin, New York Heart Association (NYHA) class, and the location of the AVF in hemodialysis (HD) patients. The cross-sectional study was performed on a cohort of 93 clinically stable HD patients. Patients with proximal AVF tend to be older, with decreased renal residual function and increased NYHA functional class. These patients were also highly anemic, had more acidosis, and had increased high-sensitivity C-reactive protein along with increased copeptin and NT-proBNP levels. These changes were also associated with significant changes in all intra-cardiac dimensions, including right ventricle, both atria, and intraventricular septum and increase in end-systolic and end-diastolic left ventricular intra-cardiac dimensions. In multiple logistic regression analysis, the only associate of copeptin was NYHA functional class. Copeptin level in HD patients depends on cardiac function and it might be involved in the pathophysiology of cardiovascular disease in these patients. Proximal AVF creation might contribute to the development or worsening of CHF in HD patients.

The problem of Lyme borreliosis infections in urban and rural residents in Poland, based on National Health Fund data.

INTRODUCTION AND OBJECTIVE: Some fragmentary studies show that the incidence of Lyme borreliosis in Poland is increasing. It has been generally accepted that the most affected are forestry workers and farmers. The aim of the study is to compare the incidence of borreliosis in urban and rural residents in 2008-2016. MATERIAL AND METHODS: Databases on Lyme borreliosis from the National Health Fund and Central Statistical Office in Poland were analyzed. For each patient, ambulatory or discharged from every hospital, the diagnosis was compulsorily reported as encoded following the International Classification of Diseases. RESULTS: A steadily increasing number of patients with borreliosis in Poland was found, which doubled in 2008 - 2016. The incidence was similar in urban and rural residents. In all the provinces in Poland, an increase in incidence of borreliosis was observed, although there were big differences between them. The highest frequency of borreliosis was in Podlasie and Warmia-Masuria provinces. The lowest incidence of borreliosis was noticed in Wielkopolska province. In the most provinces the increase in the incidence of borreliosis was steady, except Warmia-Masuria, where it was very low in 2008, and soaring since 2011. The number of cases per year between 2008 - 2016 increased in both in males and females. CONCLUSIONS: The results suggest the need for higher awareness of the risk of Lyme borreliosis in urban residents, because the incidence of Lyme borreliosis is growing independently of the place of residence. Prompt measures to prevent tick bites and appropriate education are urgently needed.

Systemic levels of MMP2/TIMP2 and cardiovascular risk in CAPD patients.

BACKGROUND/AIMS: Matrix metalloproteinases (MMPs), their inhibitors (TIMPs), oxidative stress (SOX) and kynurenine (KYN) pathway have been postulated in cardiovascular disease (CVD) progression. We hypothesized the possible association between the MMP/TIMP system, KYNs and CVD prevalence in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: We assessed MMP-2, MMP-9, TIMP-1, TIMP-2, KYN and its metabolite - quinolinic acid (QA), and SOX marker - Cu/Zn superoxide dismutase (Cu/Zn SOD) levels in CAPD patients both with and without CVD and healthy controls. RESULTS: MMP-2, TIMP-2, Cu/Zn SOD, KYN and QA were significantly higher in CAPD patients with CVD than in patients without CVD and controls. MMP-2 and TIMP-2 were positively correlated with QA and Cu/Zn SOD levels, and the strong association was between MMP-2 and TIMP-2 levels. Multiple regression analyses identified Cu/Zn SOD, TIMP-2, QA and QA/KYN ratio as the factors independently associated with MMP-2, whereas MMP-2 and Cu/Zn SOD were independent variables affecting TIMP-2 levels. CONCLUSIONS: MMP-2 and TIMP-2 concentrations were higher in CAPD patients with CVD than in patients without CVD and healthy controls. Upregulation of the MMP-2/TIMP-2 system was associated with QA levels and increased oxidative status, suggesting the connection between KYN pathway activation, arterial remodeling and CVD prevalence in uremic patients on CAPD treatment.

Possible relationship between neutrophil gelatinase-associated lipocalin, hepcidin, and inflammation in haemodialysed patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules - siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. METHODS: Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-alpha, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. RESULTS: Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 +/- 213.95 vs. 78.43 +/- 32.21 ng/ml, p < 0.001, 320.54 +/- 182.65 vs. 98.65 +/- 34.32 ng/ml, p < 0.01, 155.30 +/- 94.05 vs. 23.65 +/- 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = -0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = -0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. CONCLUSIONS: NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure.

Renal consequences of obesity.

The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity.