Hypertension and nephrology

[Examination of nitrogen monoxide syntase in hypoxia induced conditions]

RUSAI Krisztina

OCTOBER 20, 2010

Hypertension and nephrology - 2010;14(05)



Further articles in this publication

Hypertension and nephrology

[The role of vitamin D receptor and the risk reducing effect of vitamin D receptor agonists in chronic kidney disease]


[Vitamin D3 is produced in the skin and is modified in the liver and kidney to the active metabolite form, 1,25-dyhydroxyvitamin D3 (calcitriol). Calcitriol binds to a nuclear receptor, the vitamin D receptor (VDR), and activates processes that bind to vitamin D. The classical effects of vitamin D receptor activator or agonist (VDRA) therapy for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease primarily involves suppressive effects on the parathyroid gland, and regulation of calcium and phosphorus absorption in the intestine an mobilization in bone. Several VDR agonists have been developed for the treatment of osteoporosis, hyperparathyroidism secondary to chronic kidney disease (CKD), and psoriasis. Secondary hyperparathyroidism (SHPT) is a common and serious consequence of CKD. SHPT is a complex condition characterized by a decline in 1,25-dihidroxi vitamin D and consequent VDR activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drug used for treatment of SHPT (non-selective and selective VDR activators, and calcimimetics). Observational studies in hemodialysis patients report improved cardiovascular and allcause survival among those received VDRA therapy compared with those not on VDRA therapy. The survival benefits of selective VDRA paricalcitol appear to be linked to "non classical" action of VDRA, possibly through VDRA-mediated modulation of gene expression. VRDAs are reported to have beneficial effects such as anti-inflammatory and antithrombotic effects, inhibition of vascular calcification and stiffening, inhibition of vascular smooth muscle cell proliferation, and regression of left ventricular hypertrophy. VDRA are also reported to negatively regulate the renin-angiotensin system, which plays a key role in hypertension, myocardial infarction and stroke. Data from epidemiological, preclinical and clinical studies have shown that vitamin D and/or 25(OH) vitamin D deficiency is associated with increased risk for cardiovascular disease (CVD). The selective VDR agonists are associated direct protective effects on glomerular architecture and antiproteinuric effects in response to renal damage. Emerging evidence suggest that VDR plays important roles in modulating cardiovascular, immunological, metabolic and other function. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD.]

Hypertension and nephrology

[Recent developments in the diagnosis and therapy of haemolytic uremic syndrome. Part 1: Diagnosis and initial therapy]

PROHÁSZKA Zoltán, SZILÁGYI Ágnes, SZABÓ Melinda Zsuzsanna oh., RÉTI Marienn, REUSZ György

[In this summary an overview is offered on the recent developments of the investigation and the treatment of hemolytic uremic syndrome. Based on the recent developments in the understanding of the pathogenesis and on the novel diagnostics there is an increasing ability to identify the etiology of specific diagnostic sub-groups of the disease. This molecular etiology-based classification and sub-group diagnosis has substantial influence on the short-term and long-term management of the affected patients. The first part of our review focuses on the steps of first and second line diagnosis and the selection between available therapeutic options, and provides flow-charts for the daily work. The various aspects of the long-term management and disease monitoring in hemolytic uremic syndrome will be reviewed in a second article in the future.]

Hypertension and nephrology

[Biosimilar erythropoietins in nephrology - benedictio seu maledictio?]

KISS István

[Biological medicines of protein or polypeptide origin produced with biotechnology are far more complex in structure than the low molecular weight chemical ones. In conjunction with chemical drugs generic copies are completely the same, while in the field of biological medicines only similarity can be stated, as identical molecules cannot be produced. Spatial structure, isomers and side chains cause difference and for this reason these are called biosimilar drugs. Immunogenity of biosimilar drugs is very different and the risk of antibody production against them is diverse. Pure red cell aplasia, a rare side effect of erythropoietins is a life-threatening condition so every effort must be done for its prevention. Biosimilar drugs are not to be replaced with each other, and even the reference drugs should not be substituted in order to identify easily the side effects of each drug. Importantly financing should support these clinical principles namely a cheaper drug could be started as a new treatment but a former treatment should not be replaced because of cost sensitivity. It is important to provide the availability of the very expensive biologically active drugs to each patient but it is acceptable that the treatment should be as cost-effective as possible. Similarly to the generic copy program of chemical drugs biosimilar drugs are also important for the clinical practice, however their use needs appropriate regulation and farmacovigilance.]

Hypertension and nephrology

[Chronic kidney disease and atherosclerosis]


[Accelerated cardiovascular disease is a frequent complication of chronic kidney disease. Chronic kidney disease promotes hypertension and dyslipidaemia, which in turn can contribute to the progression of renal failure. Diabetic nephropathy is a leading cause of renal failure. Hypertension, dyslipidaemia and diabetes together are the major risk factors of the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease. Promoters of calcification are increased and inhibitors are reduced, which favors vascular calcification, an important cause of vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke and peripheral arterial disease.]

Hypertension and nephrology

[Kidney transplantation in Hungary, 2010]


[Hungarian kidney transplantation has been established with three milestone operations. In 1902 Emerich Ullmann showed the technical feasibility of renal transplantation on dogs, and later the living donor transplant of András Németh in 1962 and the program starting operation of Ferenc Perner in 1973 already meant the real possibility for Hungarian patients. More than 5000 kidney transplantations were done since, and the operations are now made at the four university medical schools centers. In 2009 248 renal transplantations were done in our country (Budapest: 148, Szeged: 51, Pécs: 39, Debrecen: 34), from which 24 were living donor and nine combined kidney-pancreas cases. Despite the worsening financing situation in the health care system the numbers of transplantations are stable within a 15 year period, but this means a marked decrease in international comparison. In our country, the ratio of living donation is low, there is no paired donation, incompatible transplantation, the problems of hypersensitive patients are unresolved, and there is no old-for-old program. The solution to all of these problems could be joining to Eurotransplant, which is the definite wish of the transplant society based on the positive Slovenian and Croatian examples.]

All articles in the issue

Related contents

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Clinical Neuroscience

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm


The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Clinical Neuroscience

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report


Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.