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Hypertension and nephrology

SEPTEMBER 14, 2018

[Role of ketoanalogue amino acids and diet in the treatment of patients with chronic kidney disease]

KISS István, HARIS Ágnes, DEÁK György

[Low protein diet is an important component of the non-pharmacological treatment of patients with chronic kidney disease (CKD). Along with the diet it is important to maintain appropriate energy intake to avoid malnutrition. It is recommended to supplement low protein diet (0.6-0.7 g protein/kg body weight/day) with essential amino acids and their ketoanalogues (ketoacids) in a dose of 1 tablet/8-10 kg body weight if there is a threat of protein malnutrition (eg. vegan diet). Very low protein diet (0.3-0.4 g protein/kg body weight/day) should be supplemented with ketoacids in a dose of 1 tablet/5 kg body weight. Low protein diet is recommended for patients with CKD stage 3 and progressively declining renal function, or nephrotic syndrome; in diabetic nephropathy; in CKD stage 4 and non-dialyzed CKD stage 5. Nephroprotective effect of very low protein diet is primarily expected is patients with an eGFR below 20-25 ml/min/1.73 m2 and good compliance. Dietary protein restriction may diminish acidosis and proteinuria, slow the progression of CKD and delay initiation of dialysis. Diets reduced in protein supplemented with appropriate energy intake and ketoacids are nutritionally safe. Dietary education and guidance of patients by qualified dietitians are of great importance in nephrology clinics. We illustrate the main points of our review with case reports.]

Hypertension and nephrology

DECEMBER 19, 2020

[Possibility of ARNI (angiotensin receptor-neprilysin inhibitor) treatment in hypertension]

KÉKES Ede

[The natriuretic peptide (NP) is an important endocrine, autocrine and paracrine system that is in constant interaction with RAAS and the sympathetic nervous system in order to ensure a continuous cardio-renal homeostasis. In abnormal conditions – if the pressure/volume load develops in the heart or there are some disorder in the vascular tone or in sodium-water balance, the NP system triggers the body’s defense mechanism. The neutral endopeptidase (NEP) inactivates the vasodilator NPs, bradykinin and vasoconstrictor angiotensin II and endothelin I as well. From this knowledge, the idea that inhibition of the effect of NEP (NEPg) offers a potentially beneficial option in the treatment of heart failure and hypertension was initiated, only the stimulatory effect of angiotensin II needs to be blocked. After a lengthy search, they arrived at a dualacting molecule with a beneficial effect of NEP inhibition (secubitrile) and the angiotensin II AT1 receptor antagonist valsartan (ARNI). Several clinical studies have shown that ARNI alone and in combination with other antihypertensive agents significantly reduces SBP and DBP in hypertensive patients. Its effect is also present in isolated systolic hypertension and in chronic kidney disease with high risk. Do not administer with an ACE inhibitor. Based on clinical experience to date, there is a logic expectation that ARNI will also be classified as a useful antihypertensive agent in the near future.]

Lege Artis Medicinae

MARCH 10, 2020

[Recommendations of the European Atherosclerosis Society (EAS) and the European Society of Cardiology (ESC) for dyslipidaemia. Focused on: primary prevention]

BAJNOK László

[In 2019 the European Atherosclerosis So­ciety (EAS) and European Society of Car­dio­logy (ESC) renewed their dyslipidae­mia guidelines. The new version is more progressive than the previous ones. Thus, in the low-risk, not severely hy­per­choles­te­ro­lae­mic population cholesterol-lowering medication is also suggested. Except this low-risk group, atherogenic target values, e.g. for LDL-cholesterol, were reduced by an entire category, in some cases to the lowest one. If these goals cannot be achieved with statin-monotherapy, combined treatment is recommended generally by the cholesterol inhibitor ezetimib, and in some very high-risk cases also by innovative cholesterol lowering so-called PCSK9 inhibitor. ]

Clinical Oncology

APRIL 10, 2019

[CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions]

SPRING M. Laura, WANDER A. Seth, ZANGARDI Mark, BARDIA Aditya

[Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+MBC) as well as current controversies and evolving areas of research. Recent fi ndings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the fi eld include whether all patients with HR+MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. Summary: The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.]

Hypertension and nephrology

MAY 10, 2019

[One-year persistence of fixed-dose combinations of angiotensin-converting enzyme inhibitor and calcium channel blocker in hypertensive patients]

SIMONYI Gábor, FERENCI Tamás, FINTA Ervin, IGAZ Iván, BALOGH Sándor, GASPARICS Roland, MEDVEGY Mihály

[Introduction: The most recent European guidelines for the treatment of hypertension suggest the use of renin-angiotensin-aldosterone system antagonists (RAAS inhibitors) and calcium channel blockers (CCBs) or diuretics fixed-dose combinations (FDCs) as the first therapeutic option. In antihypertensive therapy, the patient’s adherence is one of the most important factors in reducing unwanted cardiovascular events. Aim: Our aim was to assess the one-year persistence of angiotensin-converting enzyme inhibitor (ACEI) and CCB FDCs in hypertensive patients. Method: Authors have analysed the prescription database of the National Health Insurance Fund in Hungary on pharmacy claims between October 1, 2012 and September 30, 2013. Those patients were identified who filled prescriptions for FDCs of ACEI and CCBs prescribed for the first time for hypertensive patients and who had not re ceived similar drugs during the year before. Apparatus of survival analysis was used, where ‘survival’ was the time to abandon the medication. Results: 124,388 patients met the inclusion criteria. One-year persistence rate and hazard ratio (HR) of discontinua tion in patients with ramipril/amlodipine FDC was 54% (HR = 1.00, reference), perindopril/amlodipine 47% (HR = 1.30, p<0.0001), lisinopril/amlodipine 36% (HR = 1.79, p<0.0001), ramipril/felodipine 26% (HR = 2.28, p<0.0001) and trandolapril/verapamil 12% (HR = 4.13, p<0.0001). The average survival time of drug limited to 360 days was 270.2 days for ramipril/amlodipine FDC, 242.7 days for perindopril/amlodipine FDC, 211.2 days for lisinopril/amlodipine FDC, 186.3 days for ramipril/felodipine FDC and 125.7 days for trandolapril/verapamil FDC. Conclusions: The authors demonstrated that the one-year persistence of ACEI/CCB FDCs was significantly different in hypertensive patients. Ramipril/amlodipine FDC was more advantageous for patient adherence.]

Hypertension and nephrology

APRIL 24, 2020

[Possibilities and limitations. Dietary difficulties of chronic renal failure in childhood]

REUSZ György, SZABÓ Adrienn

[In chronic kidney disease (CKD), the role of the kidney in assuring homeostasis is gradually deteriorating. Besides fluid, electrolyte and hormonal disturbances, detoxification and control of blood pressure is insufficient without external help. In children, in addition to achieving equilibrium it is also essential to ensure optimal physical and cognitive/psychological development. Adequate calorie intake is a major determinant of growth during infancy. Among the therapeutic options it is essential to ensure a proper diet. In addition to reflecting the special needs of renal failure in its composition, it must be palatable for the child. Children with kidney disease should have a normal energy diet. Protein intake should not be reduced from the baseline recommendation, but lower phosphorus and high bioavailability should be preferred. A low sodium and potassium diet is recommended for a significant proportion of patients and is based on dietary advice. Further, diet planning may be problematic if the child has special dietary requirements and is in need of nasogastric tube feeding. Because diet planning is a complex task, it is difficult to achieve optimal protein supply and mineral restriction along with high energy intake. In such cases, enteral nutrition with special formulas/ drinks developed for pediatric nutrition may provide a solution.]

Clinical Neuroscience

JULY 30, 2019

A case report of Morvan syndrome

AYTAC Emrah, ACAR Türkan

Morvan syndrome is a rare disease characterized by peripheral nerve hyperexcitability, encephalopathy, dys­autonomia and significant insomnia. The patient, who was included in the present study, was followed-up at our clinics for confusion, myokymia, hyperhidrosis, epileptic seizures, tachycardia, agitation, hypokalemia, and hyponatremia. The cranial MRI of the patient demonstrated hyperintensities at the T2 and FLAIR sections of the medial temporal lobe and insular lobes. Electromyography and neurotransmission examination results were concordant with peripheral nerve hyperreactivity. Contactin-associated protein-like 2 antibodies and leucine-rich glioma inactivated protein 1 antibodies were detected as positive. The patient was diagnosed with Morvan syndrome; intravenous immunoglobulin and corticosteroid treatment was started. Almost full remission was achieved. This very rare syndrome implies challenges in diagnosis and treatment; however, remission can be achieved during the follow-up. In addition, caution is needed in the long-term follow-up of these patients regarding the development of malignancies.

Clinical Neuroscience

JANUARY 30, 2019

Additional value of tau protein measurement in the diagnosis of Creutzfeldt-Jakob disease

CSEH Katalin Edina, VERES Gábor, DANICS Krisztina, SZALÁRDY Levente, NÁNÁSI Nikolett, KLIVÉNYI Péter, VÉCSEI László, ZÁDORI Dénes

Since the definite diagnosis of Creutzfeldt-Jakob disease (CJD) can currently only be provided by autopsy, there is a special need for fine diagnostic tools in live patients to achieve accurate diagnosis as early as possible. The aim of this study was to perform a preliminary retrospective analysis on the utility of the measurement of total Tau (tTau) and some other biomarkers from the cerebrospinal fluid (CSF) of patients with rapidly progressive dementia in the diagnostic work up of CJD. Beside the assessment of relevant clinical data and the findings of electroencephalography and brain magnetic resonance imaging, the presence of 14-3-3 protein and the levels of tTau were determined by Western blot technique and enzyme-linked immunosorbent assay from the CSF of 19 patients diagnosed with rapidly progressive dementia between the period of 2004-2017 at the Department of Neurology, University of Szeged. This preliminary study provided 100% sensitivity for 14-3-3, and interestingly, only 40% specificity to support the clinical diagnosis of CJD. Regarding tTau, the sensitivity values were calculated to be 100% or 83%, whereas the specificity values were 71% or 86%, depending on the applied cut-off levels. The poor specificity of 14-3-3 is not in line with literature data and may be the result of the small number of patients in the cohort with non-prion disease, predominantly consisting of disorders with considerable tissue damage, whereas tTau presented good sensitivity and specificity values. The combined application of these and novel chemical biomarkers may increase both sensitivity and specificity to a desired level.

Lege Artis Medicinae

JUNE 07, 2021

[Lipid lowering therapy during COVID-19 pandemic]

MÁRK László

[The COVID-19 pandemic posed significant challenges to all healthcare systems of the world as created a new situations above the large number of people infected, solutions of which were lacking any previous patterns. Former experiences were specifically needed among physicians who practised usually with therapies supported by evidence based clinical experiences thus they were working along the principles of Evidence-Based Medicine. The new observations and recommendations for treating infected patients increased gradually, however they were not always well-founded by the general urgency. In this situation, physicians faced often problems of the patient’s former medications since they had to focus on the therapy of the prevalent life-threatening condition. In such cases, therapy as lipid lowering, which is inherently inimically and lightly taken, may be omitted even more often. Basic drugs of lipid lowering are statins. They are used to reduce cholesterol levels and the risk of cardiovascular events, but they have also been described as having beneficial effect on the new viral infection. In this effect, the statins beyond the well-known anti-inflammatory impact and increasing the expression of angiotensin-converting enzyme-2 further mechanisms can take part as well. These may include among others the promoted breakdown of lipid rafts, which directly inhibits the entry of coronavirus into the cell through the S protein by decreasing the level of cholesterol required for this proceeding. In a group of more than 1200 statin treated and SARS-COV-2 infected patients the overall mortality rate by the 28th day was 48% lower than among the non-statin-users. According to a meta-analysis of nearly nine thousand COVID-19-infected statin users, they had 30% lower mortality rate or serious complications. Up to date observational studies suggest that statin therapy and the administration of other lipid lowering drugs should be continued or initiated according to the guidelines also during the COVID-19 infection.]

Clinical Neuroscience

JANUARY 30, 2021

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents

SANLI Arzu, OZTURK Musa, SOYSAL Aysun, DOVENTAS Yasemin, BASOGLU Fulya, GOZUBATIK-CELIK R. Gokcen, BAYBAS Sevim

Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.