May Measurement Month 2017: an analysis of blood pressure screening in Hungary-Europe.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. The cardiovascular mortality rate in Hungary is twice as high as the European Union average. In a recent Hungarian screening programme, among those volunteers who claimed to be healthy, BP was above 140/90 mmHg in 24% and 39% in women and men, while the control rate was 45% and 36% in women and men, respectively. May Measurement Month (MMM) is a global initiative by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. In Hungary, 97 sites were set-up in primary and secondary care facilities, in pharmacies and in malls. All regions, both cities and villages were involved. A total of 3967 individuals were screened. After multiple imputation, 2052 subjects (51.8%) had hypertension. 553 (22.4%) of untreated individuals had hypertension, and 666 (44.5%) of treated individuals had uncontrolled BP. More than 50% of the screened cohort had hypertension (treated and controlled, treated and uncontrolled or untreated). By identifying almost one-third of the screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, the Hungarian part of MMM17 suggest that opportunistic screening can identify significant numbers with raised BP.

Effect of angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on erythropoiesis in patients on haemodialysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEis) improve survival; however, their effect on erythropoiesis remains a matter of debate in this population. Since insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene largely influences serum ACE activity, its effect on erythropoiesis is also anticipated. METHOD: In this multicentre, cross-sectional study of 660 patients on maintenance haemodialysis, we analysed the effect of ACEi use and ACE gene I/D polymorphism on haemoglobin levels and erythropoietin resistance. Patients were allocated in groups based on genotype and ACEi therapy. We identified 128 matched pairs with I/I and D/D genotypes. RESULT: There was no difference in haemoglobin levels between genotype groups. Haemoglobin levels were lower in patients on ACEi therapy in the entire cohort (95.5±12.1 g/l vs 97.4±13.4 g/l, p=0.02) and patients with I/D (95.2±11 g/l vs 98.2±11.9 g/l, p=0.04) and D/D (93.3±13.2 g/l vs 97.4±14.2 g/l, p=0.02) genotypes. In patient pairs treated with ACEi therapy, subjects with D/D genotype had lower Haemoglobin level (93.0±12.8 g/l vs 98.2±11.9 g/l, p=0.006) and higher erythropoietin resistance index (ERI) (199.1 vs 175.0, p=0.046) than individuals with I/I genotype. CONCLUSION: These results indicate that ACEi therapy may increase erythropoietin resistance and worsen erythropoiesis in haemodialysis patients with the D allele.

Interaction between angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin-converting enzyme inhibition on survival in hemodialyzed patients.

The association between ACE (angiotensin-converting enzyme) gene insertion/deletion (I/D) polymorphism and mortality has been inconsistently observed in earlier studies in patients on maintenance hemodialysis. We hypothesized that the effect of ACE gene I/D polymorphism on mortality may be influenced by concurrent ACE inhibitor therapy in this population. In this prospective, multicenter cohort, observational study, data was collected from 716 prevalent chronic hemodialysis patients, blood samples were genotyped for I/D single nucleotide polymorphism. Patient mortality was assessed in tree genotype groups insertion/insertion, insertion/deletion and deletion/deletion (I/I, I/D, and D/D) using multivariate Cox proportional hazard models. The most frequent genotype was I/D (42.6%), followed by D/D (37.7%) and I/I (19.7%) genotypes. The mean age was 54.9±15.5 years, 53.2% of all patients were male and in the total group the prevalence of diabetes was 19.3%. ACE inhibitor therapy was prescribed for 47.9% of all patients. The median duration of dialysis before blood sampling was 23.8 months (IQR 11.2-47.1). Patients were followed for 10 years, the median follow-up time was 29.8 months (IQR 12.6-63.4). Patient characteristics were well balanced among the genotype groups. D/D genotype, was associated with inferior survival (I/I vs D/D: log-rank test: P=0.04) in patients not receiving ACE inhibitor therapy, and the presence of this therapy diminished this difference. There was no difference in survival among unselected patients with different genotypes. In multivariate Cox regression models, D/D genotype (compared to I/I) was a significant predictor of mortality only in patients without ACE inhibitor therapy (HR 0.67, 95% CI 0.46-0.97, P=0.03). Our data suggests that hemodialyzed patients with the deletion/deletion (D/D) genotype might have inferior outcome, and ACE inhibitor therapy may be associated with improved survival in this subgroup.

Chlorine dioxide is a size-selective antimicrobial agent.

BACKGROUND / AIMS: ClO2, the so-called "ideal biocide", could also be applied as an antiseptic if it was understood why the solution killing microbes rapidly does not cause any harm to humans or to animals. Our aim was to find the source of that selectivity by studying its reaction-diffusion mechanism both theoretically and experimentally. METHODS: ClO2 permeation measurements through protein membranes were performed and the time delay of ClO2 transport due to reaction and diffusion was determined. To calculate ClO2 penetration depths and estimate bacterial killing times, approximate solutions of the reaction-diffusion equation were derived. In these calculations evaporation rates of ClO2 were also measured and taken into account. RESULTS: The rate law of the reaction-diffusion model predicts that the killing time is proportional to the square of the characteristic size (e.g. diameter) of a body, thus, small ones will be killed extremely fast. For example, the killing time for a bacterium is on the order of milliseconds in a 300 ppm ClO2 solution. Thus, a few minutes of contact time (limited by the volatility of ClO2) is quite enough to kill all bacteria, but short enough to keep ClO2 penetration into the living tissues of a greater organism safely below 0.1 mm, minimizing cytotoxic effects when applying it as an antiseptic. Additional properties of ClO2, advantageous for an antiseptic, are also discussed. Most importantly, that bacteria are not able to develop resistance against ClO2 as it reacts with biological thiols which play a vital role in all living organisms. CONCLUSION: Selectivity of ClO2 between humans and bacteria is based not on their different biochemistry, but on their different size. We hope initiating clinical applications of this promising local antiseptic.

Age-dependent parathormone levels and different CKD-MBD treatment practices of dialysis patients in Hungary--results from a nationwide clinical audit.

BACKGROUND: Achieving target levels of laboratory parameters of bone and mineral metabolism in chronic kidney disease (CKD) patients is important but also difficult in those living with end-stage kidney disease. This study aimed to determine if there are age-related differences in chronic kidney disease-mineral and bone disorder (CKD-MBD) characteristics, including treatment practice in Hungarian dialysis patients. METHODS: Data were collected retrospectively from a large cohort of dialysis patients in Hungary. Patients on hemodialysis and peritoneal dialysis were also included. The enrolled patients were allocated into two groups based on their age (<65 years and ≥65 years). Characteristics of the age groups and differences in disease-related (epidemiology, laboratory, and treatment practice) parameters between the groups were analyzed. RESULTS: A total of 5008 patients were included in the analysis and the mean age was 63.4±14.2 years. A total of 47.2% of patients were women, 32.8% had diabetes, and 11.4% were on peritoneal dialysis. Diabetes (37.9% vs 27.3%), bone disease (42.9% vs 34.1%), and soft tissue calcification (56.3% vs 44.7%) were more prevalent in the older group than the younger group (p<0.001 for all). We found an inverse relationship between age and parathyroid hormone (PTH) levels (p<0.001). Serum PTH levels were lower in patients with diabetes compared with those without diabetes below 80 years (p<0.001). Diabetes and age were independently associated with serum PTH levels (interaction: diabetes × age groups, p=0.138). Older patients were more likely than younger patients to achieve laboratory target ranges for each parameter (Ca: 66.9% vs 62.1%, p<0.001; PO4: 52.6% vs 49.2%, p<0.05; and PTH: 50.6% vs 46.6%, p<0.01), and for combined parameters (19.8% vs 15.8%, p<0.001). Older patients were less likely to receive related medication than younger patients (66.9% vs 79.7%, p<0.001). CONCLUSIONS: The achievement of laboratory target ranges for bone and mineral metabolism and clinical practice in CKD depends on the age of the patients. A greater proportion of older patients met target criteria and received less medication compared with younger patients.

Discovery and basic pharmacology of erythropoiesis-stimulating agents (ESAs), including the hyperglycosylated ESA, darbepoetin alfa: an update of the rationale and clinical impact.

Cloning of the human erythropoietin (EPO) gene and development of the first recombinant human erythropoietin (rHuEPO) drug were truly breakthroughs. This allowed a deeper understanding of the structure and pharmacology of rHuEpo, which in turn inspired the discovery and development of additional erythropoiesis-stimulating agents (ESAs). In vivo specific activity and serum half-life of rHuEPO are influenced by the amount and structure of the attached carbohydrate. Increased numbers of sialic acids on carbohydrate attached to rHuEPO correlated with a relative increase in in-vivo-specific activity and increased serum half-life. The effect of increasing the number of sialic-acid-containing carbohydrates on in-vivo-specific activity was explored. Initial research focused on solving the problem of how the protein backbone could be engineered so a cell would add more carbohydrate to it. Additional work resulted in darbepoetin alfa, a longer-acting molecule with two additional carbohydrate chains.

Serum cystatin C is a determinant of paraoxonase activity in hemodialyzed and renal transplanted patients.

BACKGROUND: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis, and possesses lactonase activity. Decreased PON1 activity was found in hemodialyzed and renal transplanted patients. Cystatin C plays a protective role in atherosclerosis, and is a new, sensitive marker of renal function. The relationship between these two markers in renal failure has not been investigated. AIMS: The goal of this study was to clarify the relationship between PON1 activity, cystatin C and homocysteine in chronic renal failure. We also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) to characterize lipid peroxidation. PATIENTS AND METHODS: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110 healthy controls (C) were involved in the study. PON1 activity and TBARS levels were measured spectrophotometrically. OxLDL level was determined with sandwich ELISA. RESULTS: There was a negative correlation between PON1 activity and cystatin C level. Homocysteine level correlated negatively with PON1 activity, and positively with cystatin C level. OxLDL and TBARS levels were significantly higher in the HD and TRX groups compared to C. CONCLUSIONS: Cystatin C may be a good predictive factor not only for homocysteine levels but for the antioxidant status in patients with renal failure and renal transplantation.

[Effectiveness of peg-interferon and ribavirin for hepatitis C in a patient with hypertension and diminished kidney function]. / A peginterferon és a ribavirin hatásossága hepatitis C-vírus-fertôzésben hipertónia és vesefunkció beszûkülése esetén.

UNLABELLED: The treatment of chronic hepatitis caused by hepatitis C virus (HCV) has got now success only in 40-60 per cent of cases with combined interferon and ribavirin therapy. In patients infected by HCV not only the liver but other organs can have alterations. The treatment should be generally applied in a one-year period, and its administration should be carefully carried out both by the patients and the doctors. It can be accompanied by several complications. Beside these the other diseases of the patient's organs can have some problems. AIM OF THE STUDY: The demonstration of a patient history with clinical success who had hypertension and renal disease. CASE REPORT: 42-year-old female patient who had hypertension and kidney diseases in her anamnesis. Her complaints started with mild abdominal symptoms in 2000. The biochemical alterations and the positive reaction with HCV-PCR test showed HCV infection. Its genotype was 1b. The patient tolerated the combined peginterferon-alfa-2a and ribavirin treatment well, between August 2006 and August 2007. She became HCV-PCR negative after six-month treatment and also at the end of therapy. DISCUSSION: The concomitant diseases of the patient made the treatment heavier, but not impossible. CONCLUSION: The elimination of HCV infection can be possible also in the case of hypertension and decreased renal function.

[Diagnosis and therapy of renal anemia]. / A renalis anaemia diagnosztikája és terápiája.

The cardiovascular state and life quality of patients suffering from chronic renal insufficiency is primarily determined by their haemostatic status. Renal anemia can positively be diagnosed if the glomerular filtration rate diminishes significantly (<60 ml/min/1,73 m 2 ). Other causes of anemia besides renal insufficiency can be excluded in these instances. The primary aim of erythropoietin treatment is to abolish the transfusion demand of patients suffering from renal insufficiency as this could lead to antibody formation and the transduction of viral infections. In case the existence of renal anemia is proved, the target values must be determined. A target value of >11 g/dl hemoglobin should be achieved for at least 85% of the patients in order to get an average hemoglobin level of 12-12,5 g/dl for the whole patient population. During the treatment of renal anemia regulating the iron metabolism of patients is of primary importance. A >5% rate of the hypochromic red blood cells in the blood circulation implies iron deficiency; but a value above 10% positively indicates iron deficiency. The transferric saturation values under 20% indicate functional iron deficiency and this indicator is a good means of following iron treatment. In the case of patients receiving dialysis parenteral input is advised because of poor iron absorption. In national clinical practice several erythropoietin products are available (erythropoietin-alpha, erythropoietin-beta, alpha-darbepoetin and continuous erythropoietin receptor activator, a new product now being introduced). When selecting the appropriate treatment strategy for each patient, the application method, the effect range and cost efficiency of the selected erythropoietin product must be taken into consideration.

[Renal insufficiency caused by medicines, diagnostic processes, toxins]. / Gyógyszerek, diagnosztikumok, mérgek okozta veseelégtelenség.

The significance of acute renal insufficiency has grown in the past decade. The increase in the prevalence and mortality of the disease has played a role in this tendency. When judging the significance of acute renal insufficiency, one cannot ignore the fact that the rate of acute renal insufficiency emerging due to medical interventions is rising. The wide-spread diagnostic processes, the interventions and the medicines also promote the emergence of acute renal insufficiency. As for prevention, it is a key task to recognize the high-risk population, assess the renal function and utilize the nephroprotective facilities.

[The treatment of the disease "hypertonia" based on the new recommendations]. / A hypertoniabetegség kezelése az úij ajánlások alapján.

Hypertonia is a widespread disease among the population, and one of the most important reasons behind the morbidity and mortality of cardiovascular diseases. In the past few years, recommendations from the American (JNC 7), the European (ESH/ESC 2003) and the Hungarian Hypertonia Associations have been published. The international and domestic recommendations are similar in that they all state that normal and optimal blood pressure is 120/80 Hgmm. The lower limit of hypertonia is specified as 140/90 Hgmm. The reduction of risks is an absolute priority in the treatment of hypertonia. Before starting the administration of medicines, the patient's risk category is identified and a target blood pressure is specified. The treatment strategy is then set up. The recommendations deal in detail with the first choice, the fixed and not fixed combinations of medicines to be administered. All three recommendations pay special attention to the determination of the indicators of preventing thrombocyte aggregation and statin treatments.

The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis.

BACKGROUND: While frequent or occasional symptomatic intradialytic hypotension (IDH) may influence patient well-being, its effects on survival-independent of comorbidities-has not previously been investigated. In this study, therefore, our objective was to assess the effect of frequent IDH (f-IDH) or occasional IDH (o-IDH) on survival. METHODS: During a 10 month run-in period in 1998, 77 patients with f-IDH (> or =10 hypotensive events/10 months, responding only to medical intervention) and 101 patients with o-IDH (1 or 2 events/10 months) were identified among all 958 patients of a dialysis network. Eighty-five patients who had no hypotensive episodes (no-IDH) during this run-in phase served as controls. Patients were followed for a median of 27 months (range: 0.3-37) and survival of patients in the three groups was compared by log-rank test. Independent association of f-IDH and o-IDH with survival, compared with no-IDH, was assessed by a proportional hazards model that included patient demographics, laboratory data and antihypertensive medication as well as comorbidity. RESULTS: Forty-five patients (58%) with f-IDH, 47 (47%) with o-IDH and 33 (39%) with no-IDH died during the follow-up. Mortality rates (deaths/100 patient years) were 37 (log-rank P = 0.013 vs no-IDH), 26 (log-rank P = 0.375 vs no-IDH) and 21 in the three groups, respectively. This indicates significantly decreased survival in patients with f-IDH as compared to those with no-IDH. In multivariate proportional hazards regression, however, where age, sex, time spent on dialysis, presence of coronary heart disease, diabetes, Kt/V, albumin level and use of beta-blockers, calcium-channel blockers and long-acting nitrates has been adjusted for, neither f-IDH nor o-IDH was associated with survival. CONCLUSIONS: Mortality in patients with f-IDH is significantly higher than in those without such events. After adjustments for covariates, however, there is no independent effect of frequent or occasional episodes of IDH on mortality.

Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension.

BACKGROUND: Symptomatic dialysis hypotension (DH) continues to be a common problem. By comparing patients prone and resistant to DH, several dialysis session and patient related characteristics have been identified that confer susceptibility to DH. Less is known, however, about the comparison of patients with frequent and only occasional DH. The aim of the study was to compare clinical and dialysis-session- (complicated by hypotension) related data between those with frequent (fDH) and those with occasional dialysis hypotension (oDH). METHODS: Nine hundred and fifty-eight patients at 11 dialysis units were followed for 10 months and characteristics of patients with fDH (> or = 10 hypotensive events necessitating medical intervention) (n = 96) were compared to that of patients with oDH (1 or 2 events/10 months) (n = 130). Significant and independent predictors of fDH were obtained by multivariate logistic regression. RESULTS: Significant differences between fDH vs. oDH patients were older age (64.4 vs. 56.9 years, p < 0.001), more females (66 vs. 46%, p < 0.005) in fDH. More fDH patients had diabetes (27 vs. 15%, p < 0.05) and less had glomerulonephritis (15 vs. 35%, p < 0.001) as the cause for ESRD. Coronary artery disease (68 vs. 50%, p < 0.01) and long-acting nitrate treatment (51 vs. 30%, p < 0.001) was more frequent while treatment with ACEI (33 vs. 48%, p < 0.05) or Ca-channel blockers (40 vs. 53%, p < 0.05) were less frequent in patients with fDH. Patients with fDH had higher serum phosphorus levels (1.99 vs. 1.79 mmol, p < 0.005). Dialysis session related data were similar but the hypotensive episode occurred earlier during dialysis in fDH (136 vs. 156 min, p < 0.01). In multivariate analysis, significant independent predictors of fDH were older age (OR = 1.04 [1.02-1.07]), lack of glomerulonephritis as renal diagnosis (2.63 [1.18-5.87]), high phosphorus levels (5.0 [2.45-10.0]), lack of use of Ca-channel blockers (2.09 [1.12-3.91]), and the use of nitrates (2.38 [1.24-4.55]). CONCLUSION: Features of the dialysis sessions complicated by DH seem to be similar between patients with fDH and oDH, while patient characteristics such as older age, renal diagnosis other than glomerulonephritis, higher serum phosphorus levels, use of nitrates, and lack of use of calcium channel blockers are significantly and independently associated with fDH.