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Hypertension and nephrology

FEBRUARY 20, 2019

[The importance of statin therapy in hypertension]

PARAGH György, PÁLL Dénes

[Hypertension and hypercholesterolaemia often co-occur and promote early cardiovascular disease. Previous studies have shown that antihypertensive treatment may be more effective if LDL cholesterol is also reduced. This may be due to the increased expression of angiotensin-1 receptor in hypercholesterolaemia, which increases peripheral vascular resistance through angiotensin-2, and adversely affects endothelial and smooth muscle cells. Other authors indicate that high cholesterol levels increase the production of angiotensin-2 through the activation of the chymase system. High cholesterol levels increase the amount of circulating oxidized LDL which binds to the transmembrane oxidized LDL receptor (LOX- 1) also activates the angiotensin-1 receptor. In addition, angiotensin-2 has an effect on intracellular cholesterol synthesis by enhancing the key enzyme of the synthesis of intracellular cholesterol, HMG-CoA reductase. The authors present the studies that support cholesterol lowering can contribute to lowering blood pressure and other major meta-analyses in which the beneficial effects of cholesterol lowering and lipid lowering on blood pressure reductions were not proven. In the background, it may well be that these studies are not designed to evaluate the effect of cholesterol-lowering drugs on hypertension in patients with hypercholesterolaemia, and non-statin-treated patients are not randomized.]

Hypertension and nephrology

FEBRUARY 20, 2019

[Carvedilol in chronic kidney disease]

CSIKY Botond

[Chronic kidney disease (CKD) is endemic affecting 850 million people worldwide. Adequate antihypertensive treatment slows the progression of the kidney disease and also decreases the mortality of this population. Because of the comorbidities and the high cardiovascular risk beta-blockers have to be administered frequently in these patients. Carvedilol is a 3rd generation non-selective beta-blocker with alpha- 1 receptor blocking and antioxidant properties. It is metabolically neutral, it does not increase the risk of new onset diabetes and it does not increase the patients’ body weight. In some animal models of CKD and in several human CKD studies carvedilol has shown to have nephroprotective properties and it also decreased the cardiovascular risk in combination therapies.]

Lege Artis Medicinae

DECEMBER 10, 2018

[Experimental investigation of the complex energy balance]

GARAMI András

[The complex energy balance includes maintenance of both normal body mass and body temperature. In the homeostasis regulation it is important that the activities of several physiologic processes are balanced with each other, for example, the balance between food intake and energy expenditure is crucial to maintain normal body mass, while the balance between heat production and heat loss is vital in determining body temperature. Obesity and loss of body weight, as well as fever and hypothermia are consequences of the dysregulation in energy balance. In our research, we studied receptorial and neurohumoral mechanisms involved in the maintenance and in the impairment of energy balance. This paper gives an overview of our most important findings, which served as the basis of the application submitted to and awarded with 3rd prize by the Prof. Dr. Laszlo Romics Memorial Foundation. We review the physiologic role of transient receptor potential channels, mostly of vanilloid-1 (formerly: capsaicin receptor) in the regulation of body temperature and body mass. Among the neuropeptides which take part in the maintenance of energy balance, we present the thermoregulatory effects of alpha-melanocyte stimulating hormone and pituitary adenylate cyclase-activating polypeptide. Last, among the molecular mechanisms of systemic inflammation, which is characterized by thermoregulation disorders (e.g., fever, hypothermia), we recap the role of the vanilloid-1 and neurokinin-1 receptor, and bilirubin.]

Lege Artis Medicinae

OCTOBER 20, 2018

[Gene modified T cells against cancer]

SZÖŐR Árpád

[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Hypertension and nephrology

JUNE 10, 2018

[Antihypertensive effect of rilmenidine focusing on the Hungarian multicenter trial VERITAS]

FARSANG Csaba, FINTA Ervin

[Summary in the antihypertensive therapy, in addition to the RAS-blockers (ACE-inhibitors or ARBs), calcium antagonists and thizid-like diuretics, other antihypertensive drugs with different mechanisms of actions, such as the imidazoline I1 receptor agonists, are beneficially used. Several international and Hungarian studies showed the results of the effects of these agents. Authors emphasize the effects of the VERITAS study showing that in hypertensive patients the imidazoline I1 receptor agonist, rilmenidine significantly decreased the office blood pressure as well as the blood pressure measured by ambulatory blood pressure monitoring (ABPM). The white-coat reaction and left ventricular hypertrophy (LVH) were also decreased. In a separate study involving hypertensive subjects rilmenidine significantly increased baroreflex sensitivity. This effect may contribute - mainly during daytime - to the antihypertensive effect. Authors summarise the most important actions of rilmenidine, and the selected publications on the results of the Hungarian and international investigations.]

Hypertension and nephrology

APRIL 20, 2018

[Dietary treatment of dialysis patients]

ZAKAR Gábor

[Adequate nutritional indices and intake are the corner stone of long term success of renal replecement therapies (hemo- and peritoneal dialysis, transplantation) characterized by favourable survial rates and a good quality of life. There has been no major change in basic principles of nutritional prescription (protein, energy, fluid intake, restriction of sodium, potassium and phosphorous), increasing emphasis has been placed on the reduction of calcium load and ”native” vitamin-D therapy in these patients. Less avareness has been put however in the past ten years (according to recent metaanalyses) on the role and replacement of the full scale of vitamins, in spite of their occasionally altered metabolism and replacement-requirements in ESRD patients. Usually there is a need for their replacement, but some of them are represented in abundant, sometimes toxic amounts in commercially available multivitamin preparates. With in the scope of general aspects of nutrition in ESRD patients, the article gives a detalied overview of their multivitamin recommendations and alternatives of a specified substition.]

Hypertension and nephrology

MARCH 20, 2018

[Nebivolol’s unique molecule structure and its effect onthe quality of life]

KERKOVITS Gábor

[The β receptor blockers have very different effects depending on their receptor selectivity, ISA effect, which gives a wide opportunity of beneficial therapeutic choice. Resulting from its unique molecule structure nebivolol has its unique effects. It consists two isomers in 1:1 ratio. D-nebivolol is a highly β1 receptor blocker, while l-nebivolol causes NO release resulting vasodilatation. As a result of this dual effect, nebivolol more strongly reduces the blood pressure. The pressure reducing effect of nebivolol is stronger than 25 mg of atenolol, and is equal with the effect of 100 mg of atenolol. Nebivolol has a significantly higher responders’ rate than bisoprolol, and significantly fewer adverse effect. Comparing to losartan nebivolol produces significantly higher reduction in systolic and in diastolic blood pressure as well. Nebivolol has beneficial haemodynamic effects. It raises the stroke volume by 20.6 percent, the cardias output by 7.1 per cent, the ejection fraction by 7.8 per cent while reduces the peripheral resistance by 13.2 per cent. Both at rest and during exercise nebivolol cases significantly higher reduction in pulmonary wedge pressure than atenolol. Nebivolol has a better profile of adverse effects. The following adverse effects were observed: fatigue in 1.3 per cent, cold extremities in 0.8 per cent, impotence in 0.08 per cent and dyspnea in 0.05 per cent. It has also a beneficial effect on erectile dysfunction. It cases a significant elevation in erectile dysfunction score from 17.22 to 22.09. The number of sexual activity also raised from 3.41 to 6.38 during nebivolol treatment. The prevalence of erectile dysfunction is also significantly lower as compared to any β receptor blocker. Nebivolol has a synergic effect on PDE5 blockers, raises the cGMP concentration in the erectile tissue. There is also a significant difference among the β receptor blockers in the reduction of exercise tolerance. The nonselective β receptor blocker cause 40 per cent, carvedilol 35 per cent, the β1 selective receptor blocker 25 per cent while nebivolol 6 per cent reduction in the duration time.]

Hypertension and nephrology

FEBRUARY 20, 2018

[Therapy of pathological phosphate metabolism in chronic kidney disease]

LADÁNYI Erzsébet, DEÁK György, TISLÉR András, SZABÓ András

[The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline update for Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) was published in the summer of 2017 and has become a very important guidance of the complex therapy of patients with CKD. It is well known that, besides infections, cardiovascular diseases in close causal relationship with CKD-MBD are leading mortality factors of patients with CKD. Therefore the publication of the new international guideline is especially important. A Nationwide Professional Advisory Board summoned upon the initiative of the Hungarian team of Sanofi-Aventis had its assembly in September 2017 focusing on the current approaches of the therapy of calcium-phosphate metabolism in CKD patients in Hungary. Board members compared the differences between the 2009 and 2017 KDIGO guidelines and reviewed the 2011 Hungarian CKD-MBD recommendation and the relevant financing protocol. Board members assessed the applicability of the new guideline to current Hungarian practice. As compared to the previous 2009 guideline, although a number of issues were revised and modified in the light of new research and clinical results in the new 2017 guideline, most of the recommendations are still applicable tooure very day practice. It is a fundamental requirement to keep to the new guideline including the modified recommendations to optimize the long term life expectancy and quality of life of patients with CKD. The purpose of this article is to compare the 2009 and 2017 KDIGO guidelines in terms of calcium-phosphate metabolism and the treatment of hyperphosphataemia focusing on the new or modified guideline recommendations in order to assess the feasibility of their implementation in Hungarian practice. Based on available evidence and the new KDIGO guideline, board member sout lined the direction of changes of the Hungarian CKD-MBD protocol and the prescription rules of the related medications.]

Clinical Oncology

SEPTEMBER 10, 2017

[Challenges in Molecular Targeted Therapy for Gastric Cancer: Considerations for Effi cacy and Safety]

KEI Muro

[The Cancer Genome Atlas Research Network recently proposed a molecular classifi cation for gastric cancer (GC) into four subtypes based on comprehensive evaluation. While the mechanisms of molecular targeted therapies in GC were confi rmed by multiple clinical studies, only a limited number of therapeutics for GC have been approved to date. In this systematic review of the available literature, we discuss the completed and ongoing clinical trials of molecular targeted therapies in patients with GC, with a focus on their effi cacy and safety. Results of recent studies clearly demonstrated that trastuzumab and ramucirumab, monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF), respectively, improved overall survival (OS) in GC with manageable safety profi les. Careful surveillance of ongoing clinical trials and timely profi ling and monitoring of genetic signatures are imperative to establish a strong foundation for precision medicine in GC.]