Hypertension and nephrology

[Multi-photon fluorescence microscopy in the revealance of kidney physiology]

PRÓKAI Ágnes1, BERTA Nóra1, VANNAY Ádám1,2, SZIKSZ Erna1,2, KIS-PETIK Katalin3, FEKETE Andrea1,2, TOMA Ildikó4, TULASSAY Tivadar1,2, KELLERMAYER Miklós3, PETI-PETERDI János4, SZABÓ J. Attila1

FEBRUARY 20, 2012

Hypertension and nephrology - 2012;16(01)

[In this review we discuss the importance of the multi-photon fluorescence microscopy in the relevance of kidney physiology. Most functions of the kidney, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis and blood pressure are achieved by complex interactions between multiple renal cell types and previously inaccessible structures that have been difficult to study. Multi-photon fluorescence microscopy offers an advanced imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time with submicron resolution. This article reviews the application of multi-photon imaging technology that provided the most complex, spatial and temporal portrayal of renal function, depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology such as glomerular structure and function, tubular transport, tubular-vesicular interaction and the intrarenal renin-angiotensin system.]

AFFILIATIONS

  1. Semmelweis Egyetem, Általános Orvostudományi Kar, I. Sz. Gyermekgyógyászati Klinika, Budapest
  2. MTA-SE, Gyermekgyógyászati és Nefrológiai Kutatócsoport, Budapest
  3. Semmelweis Egyetem, Általános Orvostudományi Kar, Biofizikai és Sugárbiológiai Intézet, Budapest
  4. Departments of Physiology & Biophysics and Medicine, University of Southern California, Los Angeles, USA

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Hypertension and nephrology

[Functional and morphologic changes in patients with new-onset dyslipidemia after transplantation]

BORDA Bernadett, LENGYEL Csaba, VÁRKONYI Tamás, SZABÓ Viktor, SZEDERKÉNYI Edit, LÁZÁR György

[The principal risk factors for cardiovascular mortality after transplantation are hyperglycemia, hypertriglyceridemia, immunosuppressive therapy, obesity, and smoking. Among 115 patients, we assessed the risk factors for new-onset dyslipidemia, and their effects on the function and histopathology changes in the allografts one year after transplantation. Evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal versus new-onset dyslipidemia patients (p=0.002). The difference in body mass index was significant one year after kidney transplantation when comparing normal with new-onset dyslipidemia patients (p=0.02). The trigliceride levels were significantly higher among those on cyclosporine- A than those on tacrolimus (3.02±1.51 mmol/l vs 2.15±1.57 mmol/l, p=0.004). The difference also proved to be significant for the total cholesterol level: 5.43±1.23 mmol/l versus 4.42±1.31 mmol/l respectively (p=0.001). In regard to allograft function there was no significant difference one year after transplantation between the normal and new-onset dyslipidemia patients. When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy among new-onset dyslipidemia than normal function patients. Disruption of lipid homeostasis is known to severely damage the allograft. Without timely recognition and treatment, these conditions may not only lead to irreversible damage in the allograft, but also increase cardiovascular risk.]

Hypertension and nephrology

[Prominents in Hungarian nephrology Professor Gyula Petrányi (1912-2000). Part II]

SZALAY László

[A nation can only survive and keep its identity through its traditions. This is why the initiative to launch this series coming from professor János Radó is worthy of attention. Gyula Petrányi is an outstanding personality in 20th century internal medicine, to be more precise in nephrology and immunology, his activity being wide-ranging. The first part of the current summary of his work deals with a tribute to his personality, and his role in immunomodularity treatment in glomerulonephritis. The second part shall cover his role in spreading renal biopsy, screening and caring kidney patients, dialysis, in developing kidney patients’ care, furthermore in clinicopharmacology and renal transplantation.]

Hypertension and nephrology

[Chronotherapy of hypertension - individualized treatment according to the circadian blood pressure profile]

SZAUDER Ipoly, UJHELYI Gabriella

[The circadian (24 h) rhythm shows great importance in the pharmacotherapy of hypertension. There is growing interest in how to best tailor the treatment of hypertensive patients according to the circadian blood pressure pattern of each individual. Significant administration-time differences are in the chronokinetics of antihypertensive medication. The therapeutic coverage and efficacy of different antihypertensive drugs are all markedly dependent on the circadian time of drug administration. Administration of ACE inhibitors, ARBs, doxazosin and aspirin at bedtime, as opposed to upon wakening, results in an improved diurnal/nocturnal blood pressure ratio (recommended for nondipper type of hypertension). Other antihypertensive medications: calcium channel blockers and β receptor blockers are non effective at the circadian blood pressure pattern. Chronotherapy provides a means of individualizing the treatment of hypertension according to the circadian blood pressure profile of patients and constitutes a new option to optimize blood pressure control and reduce the risk of cardiovascular disease and the risk of end organ injury.]

Hypertension and nephrology

[Guidelines and clinical practice: clinical audit of CKD-MBD in Hungarian dialyzed patients]

KISS István, KISS Zoltán, SZABÓ András, SZEGEDI János, BALLA József, LADÁNYI Erzsébet, CSIKY Botond, ÁRKOSSY Ottó, TÖRÖK Marietta, TÚRI Sándor, KULCSÁR Imre

[Patients suffering from chronic kidney disease reach the end-stage renal disease in ever growing numbers and this necessitates the start of their dialysis treatment. The alteration of bone and mineral metabolism together with the development of the consequent organ damages starts in early stages of the chronic kidney disease. The goal of our present trial was to survey the alterations or characteristics (laboratory results, concomitant diseases and treatment practice in Hungary) of the calcium (Ca) and phosphate (PO4) metabolisms [mineral-bone disorder occurring in chronic kidney disease (CKD-MBD) or formerly known as secunder hyperparathyreosis or renal ostedistrophy] in patients chronically treated with dialysis. We collected and analyzed data/results from 5334 chronically dialyzed patients. We categorized the patients into different groups according to the guidelines of CKD-MBD so basically by the level of serum calcium and parathormone (PTH) (se-Ca level is below or above 2.4 mmol/l; PHT level is below 65 pg/ml, between 65-150, 150-300, 300-500, 500-800 pg/ml or above 800 pg/ml) and then the characteristic variances were compared. The two most frequent primary causes of end-stage renal disease are hypertension (23%) and diabetes mellitus (22%). Serum calcium level was below the upper limit of the normal range (Ca <2.4 mmol/l) in the greatest proportion of our patients (n=4386), while the parathormone level was elevated (PTH >500 pg/ml) in large portion of patients (n=833). Likewise in a significant part of our patients (44.9%) the parathormone level was low (PTH <150 pg/ml). The concurrent pathological elevation of both the serum calcium and the parathormone levels was found in only a minority of the patients (n=150; 2.8%). All of the drugs influencing calcium-phosphate and parathormone levels were already accessible during the time of origin of the trial in Hungary, although the financial limitations significantly affected their prescription. This is one of the reasons why local treatment practice was not fully aligned with guidelines. On the other hand the application of native vitamin D had an especially low prevalence. To sum up, our results match the European practice on the whole, although we definitely need improvement in reaching the treatment targets and also the clinical treatment practice leading to it. We will prepare a proposal for further analysis and longterm extension of this trial.]

Hypertension and nephrology

[Infections associated to vesicoureteral reflux disease in children below 1 year of age: the infulence of continuous antibiotic prophylactic therapy on the prevalence of resistant pathogenic bacteria]

MÁTTYUS István, KENESEI Éva, VÁSÁRHELYI Barna

[Background: The primary goal when children with vesicoureteral reflux disease (VUR) are treated is the prevention of pyelonephritis and persisting renal damage. Continuous antibiotic prophylaxis (CAP) is usually applied to reach this aim. The selection of resisting pathogens is the major risk of CAP. The aim of our survey was to describe the patterns of pathogenic strains leading to pyelonephritis in patients treated with and without CAP. Patients and method: The pathogenic strains implicated in pyelonephritis were identified in 48 and 56 children below 1 year of age who were treated with or without CAP, respectively, between years 2006 and 2011. Results: Breakthrough urinary tract infections developing in the presence of CAP are more frequently (with about a double risk) caused by polyresistant bacteria compared to infections that emerged without CAP. Nevertheless, it should be noted that the prevalence of resistant pathogens was about 40% even in infants without CAP. Discussion: The pattern of pathogenic strains leading to pyelonephritis alters significantly even in the cohort of children below 1 year of age treated with CAP to prevent infections associated to VUR. The risk may be decreased through the rational use of antibiotics. To reach this goal national guidelines on VUR should be updated and the role of additional non-antibiotic treatment should be established.]

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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

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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

[Advanced Parkinson’s disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]

TAKÁTS Annamária, ASCHERMANN Zsuzsanna, VÉCSEI László, KLIVÉNYI Péter, DÉZSI Lívia, ZÁDORI Dénes, VALIKOVICS Attila, VARANNAI Lajos, ONUK Koray, KINCZEL Beatrix, KOVÁCS Norbert

[The majority of patients with advanced Parkinson’s disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson’s disease; the proportion of Parkinson’s patients with advanced Parkinson’s disease, the referral process, and the clinical features used to characterize advanced Parkinson’s disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson’s patients identified as advanced patients according to physician’s judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson’s disease status was assessed with Unified Parkinson’s Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson’s disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. Overall, 2627 patients with Parkinson’s disease from 126 sites were documented. In Hungary, 100 patients with Parkinson’s disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson’s disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson’s disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). Physicians in Hungarian movement disorder centers assessed that half of the Parkinson’s patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson’s disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.]

Hypertension and nephrology

[Polycystic kidney]

DOLGOS Szilveszter, TÁRNOKI Ádám Domonkos, TÁRNOKI Dávid László

[The most common monogenic nephropathy is a congenital, cystic, bulky process in the kidney that leads to a gradual deterioration in renal function. Renal failure is often associated with cystic liver or pancreatic lesions, cerebral artery aneurysm, or mitral prolapse.]

Clinical Neuroscience

Risk factors for ischemic stroke and stroke subtypes in patients with chronic kidney disease

GÜLER Siber, NAKUS Engin, UTKU Ufuk

Background - The aim of this study was to compare ischemic stroke subtypes with the effects of risk factors, the relationship between grades of kidney disease and the severity of stroke subtypes. Methods - The current study was designed retrospectively and performed with data of patients who were hospitalised due to ischemic stroke. We included 198 subjects who were diagnosed with ischemic stroke of Grade 3 and above with chronic kidney disease. Results - In our study were reported advanced age, coronary artery disease, moderate kidney disease as the most frequent risk factors for cardioembolic etiology. Hypertension, hyperlipidemia, smoking and alcohol consumption were the most frequent risk factors for large-artery disease. Female sex and anaemia were the most frequent risk factors for small-vessel disease. Dialysis and severe kidney disease were the most frequent risk factors in unknown etiologies, while male sex, diabetes mellitus, prior stroke and mild kidney disease were the most frequent risk factors for other etiologies. National Institute of Health Stroke Scale (NIHSS) scores were lower for small-vessel disease compared with other etiologies. This relation was statistically significant (p=0.002). Conclusion - In order to improve the prognosis in ischemic stroke with chronic kidney disease, the risk factors have to be recognised and the treatment options must be modified according to those risk factors.

Hypertension and nephrology

[Prevalence of bone abnormalities and soft tissue calcification and their determining factors in dialyzed patients]

KISS Zoltán, AMBRUS Csaba, SZABÓ András, SZEGEDI János, BALLA József, TÖRÖK Marietta, LADÁNYI Erzsébet, CSIKY Botond, ÁRKOSSY Ottó, TÚRI Sándor, KULCSÁR Imre, KISS István

[Disturbances of bone and mineral metabolism are frequent complications of chronic kidney disease. In the last decades, increasing evidence of both pathophysiological and epidemiological nature support the relationship between bone disease and soft tissue calcification. In this current research, we analysed characteristics, determining factors and relationship of these two complications in a nationwide, cross-sectional cohort of dialysed patients. We collected demographical data (age, gender, body weight, height, diabetes, type of dialysis), laboratory results (serum parathormone, calcium, phosphat, albumin levels) and the presence of diabetes mellitus, bone abnormalities and soft-tissue calcification in patients on maintenance dialysis in 2010. The prevalence of bone abnormalities and soft tissue calcification followed similar pattern: both prevalences were high when parathormone <150 pg/ml (42.9% and 51.5%, respectively) or >500 pg/ml (44.2% and 55.5%) and they were significantly lower when parathormone was between 150-500 pg/ml (30.7% and 47.4%). In a multivariate logistic regression model, independent predictors of bone abnormalities were low (<150 pg/ml) and high (>500 pg/ml) parathormone levels (p<0.001), orhemodialysis (vs peritoneal dialysis) (p<0.001), age (p<0.001) and diabetes (p<0.001). In a similar statistical model, predictors of soft tissue calcification were also low (<65 pg/ml) (p<0.01) and high (>500 pg/ml) parathormone levels (p<0.001), hemodialysis (p<0.001), age (p<0.001), diabetes (p<0.001) and serum calcium level greater than 2.4 mmol/l (p<0.05). In summary, there was a U-shaped relationship between increasing serum parathormone levels and prevalence of bone abnormalities and soft tissue calcification in ESRD patients on maintenance dialysis. Further research and long term follow up are needed in order to reveal more detailed relationship among the two diseases and their determining factors.]