Publications by authors named "Eva Kis"

32 Publications

Prognostic Value of Early Risk Stratification in Pediatric Pulmonary Arterial Hypertension.

Transplant Proc 2021 Feb 20. Epub 2021 Feb 20.

Gottsegen György National Institute of Cardiology, Pediatric Heart Center, Budapest, Hungary.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening disease with risk stratification-based treatment strategy in adults. Although the risk factors have been studied individually in children, effective risk stratification is still lacking. We have tested the prognostic accuracy of pediatric PAH risk factors in our patient group.

Patients And Methods: Records of 58 PAH patients treated between 1995 and 2019 were reviewed retrospectively. Median age at diagnosis was 4.2 years (range, 0.1-16.1 years), and follow-up was 5.4 years (range, 0.01-24.1 years). Data collected at diagnosis were demographics, World Health Organization functional class, evidence of right ventricular failure, and parameters of echocardiography and cardiac catheterization.

Results: Mortality was 29% and 33% reached the composite endpoint. Patients with idiopathic PAH (n = 12) had increased risk of mortality compared with the congenital heart disease-associated PAH group (n = 32) (P = .0024). Neither the initial World Health Organization functional class staging nor the echocardiographic parameters significantly predicted the prognosis. The number of risk factors had no significant prognostic value either. In contrast, patients with higher pulmonary vascular resistance index (PVRI) had significantly increased risk (each 10 Wood units ⋅ m increase in PVRI being associated with 49.1% higher hazard, P = .0048).

Conclusions: Survival analysis showed that PAH etiology might be an important determinant in pediatric PAH risk stratification. We confirmed that PVRI has predictive value in prognostic assessment. We could not establish the prognostic value of nonweighted single risk factors or their combination to predict pediatric PAH outcome due to the low sample size, but these results indicate that such studies are warranted.
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http://dx.doi.org/10.1016/j.transproceed.2021.01.047DOI Listing
February 2021

Distance measurement for pulse wave velocity estimation in pediatric age: Comparison with intra-arterial path length.

Atherosclerosis 2020 06 18;303:15-20. Epub 2020 May 18.

Istituto Auxologico Italiano, IRCCS, Cardiology Unit, Milan, Italy.

Background And Aims: Central pulse wave velocity (PWV) is a marker of arterial stiffness and is calculated by dividing the pulse wave travel distance by the transit time. However, there is no consensus as to the ideal distance measurement in children. The aim of our study was to identify the more reliable method to assess the distance measurement in the pediatric age.

Methods: Carotid-femoral PWV was measured by applanation tonometry in 988 healthy children aged 6.5-19.9 years. Two different surface distances were assessed: the subtraction method, representing the distance from the suprasternal notch to the femoral artery minus the distance from the carotid artery to the suprasternal notch, and the direct method, consisting of 80% of the distance from the carotid artery to the femoral artery. Both these methods were compared with the actual path length determined by magnetic resonance imaging (MRI) in 31 children.

Results: Subtraction and direct methods were significantly correlated in patients aged <14 years and the corresponding PWV values showed a good agreement. In children aged ≥14 years, a significant difference between the two methods was found: subtraction - direct distance = -45 ± 28 mm, with a significant difference in the resulting PWV values = -0.57 ± 0.35 m/s (p < 0.0001). This result was confirmed by MRI, showing a 10% overestimation in distance measurement by the direct method in subjects aged ≥14 years, resulting in a significantly higher PWV.

Conclusions: These data suggest a greater reliability of the subtractive method of distance measurement compared to the direct method in children.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.04.026DOI Listing
June 2020

Evaluation of a child with suspected nephrolithiasis.

Curr Opin Pediatr 2020 04;32(2):265-272

Pediatric Heart Center, Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary.

Purpose Of Review: As the incidence of nephrolithiasis in children doubles every 10 years it is becoming a common disease associated with significant morbidity along with considerable economic burden worldwide. The aim of this review is to summarize current data on the epidemiology and causes of renal stones in children and to provide a frame for the first clinical evaluation of a child with suspected nephrolithiasis.

Recent Findings: Dietary and environmental factors are the driving force of changing epidemiology. Diagnosis should be based on medical history, presenting signs, examination, first laboratory and radiological workup. Ultrasound should be the initial diagnostic imaging performed in pediatric patients while low-dose computed tomography is rarely necessary for management. Metabolic factors including hypercalciuria, hypocitraturia, low fluid intake as well as specific genetic diseases should be explored after the resolution of initial signs and symptoms.

Summary: Appropriate initial evaluation, imaging technique, identification of risk factors and other abnormalities are essential for early diagnosis and prevention of stone-related morbidity in children with suspected nephrolithiasis.
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http://dx.doi.org/10.1097/MOP.0000000000000880DOI Listing
April 2020

Pediatric radiology crossing continents.

Authors:
Eva Kis

Pediatr Radiol 2021 Apr 22;51(4):574-580. Epub 2020 Jan 22.

Semmelweis University, Üllői út 26, Budapest, 1085, Hungary.

This paper will discuss, from a subjective perspective, aspects of paediatric radiology in different parts of the world. A small survey was conducted to improve our understanding of radiologic care and to explore the current status of paediatric radiology worldwide. As part of this survey, the number of paediatric radiologists and radiologists was compared to the population and to the number of children in 34 countries. The number of paediatric radiologists varied between 0 and 50 per million children. In general, the proportion of paediatric radiologists compared to radiologists is poor, even in countries with an aging population. Unfortunately, developing countries are severely underserved in terms of radiology, while paediatric radiology is almost nonexistent. The author, based on her experiences as a volunteer paediatric radiologist in Malawi, India, Cambodia and Tanzania, highlights some of the difficulties in radiologic care in developing countries. The author's personal experiences and the survey both suggest that the need for paediatric radiology is high across the world, but the supply is not sufficient, especially in developing countries, when compared to developed countries.
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http://dx.doi.org/10.1007/s00247-019-04598-9DOI Listing
April 2021

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

Nephrol Dial Transplant 2019 11;34(11):1932-1940

Department of Pediatric Nephrology, Gazi University, Ankara, Turkey.

Background: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment.

Methods: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias.

Results: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings.

Conclusions: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.
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http://dx.doi.org/10.1093/ndt/gfz069DOI Listing
November 2019

Cardiovascular Risk Assessment in Pediatric Liver Transplant Patients.

J Pediatr Gastroenterol Nutr 2019 03;68(3):377-383

First Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Objectives: Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children.

Methods: A total of 42 LT recipients (21 men, age 9.93 ± 3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed.

Results: Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%.

Conclusions: Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.
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http://dx.doi.org/10.1097/MPG.0000000000002196DOI Listing
March 2019

Longitudinal Deformation of the Right Ventricle in Hypoplastic Left Heart Syndrome: A Comparative Study of 2D-Feature Tracking Magnetic Resonance Imaging and 2D-Speckle Tracking Echocardiography.

Pediatr Cardiol 2018 Aug 10;39(6):1265-1275. Epub 2018 May 10.

Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Arnold-Heller-Street 3, Building 9, 24105, Kiel, Germany.

In hypoplastic left heart syndrome (HLHS), long-term outcome is closely related to right ventricular function. Echocardiography and magnetic resonance imaging (MRI) are routinely used for functional assessment. MRI 2D-tissue feature tracking (2D-FT) allows quantification of myocardial deformation but has not yet been applied to HLHS patients. We sought to investigate the feasibility of this technique and to compare the results to 2D-speckle tracking echocardiography (2D-STE). In routine MRI 2D anatomical four chamber view, cine images were recorded in 55 HLHS patients (median age 4.9 years [1.6, 17.0]). Regional and global peak systolic longitudinal strain (LS) and strain rate (LSR) were determined using 2D-FT software. Echocardiographic four chamber view was analyzed with 2D-STE. Visualization of all myocardial segments with MRI was excellent, regional, and global LS and LSR could be assessed in all data sets. In 2D-STE, 28% of apical segments could not be analyzed due to poor image quality. Agreement of 2D-FT MRI and 2D-STE was acceptable for global LS, but poor for global LSR. In MRI, regional LS was lower in the septal segments, while LSR was not different between the segments. GLS and GLSR correlated with ejection fraction (GLS: r = - 0.45 and r < 0.001, GLSR: r = - 0.34 and p = 0.01). With new post-processing options, the assessment of regional and global LS and LSR is feasible in routine MRI of HLHS patients. For LS, results were comparable with 2D-STE. The agreement was poor for LSR, which might relate to differences in temporal resolution between the two imaging modalities.
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http://dx.doi.org/10.1007/s00246-018-1892-xDOI Listing
August 2018

Cardiac Magnetic Resonance Imaging of the Myocardium in Chronic Kidney Disease.

Kidney Blood Press Res 2018 8;43(1):134-142. Epub 2018 Feb 8.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Early stages of chronic kidney disease (CKD) are often underdiagnosed, while their deleterious effects on the cardiovascular (CV) system are already at work. Thus, the assessment of early CV damage is of crucial importance in preventing major CV events. Myocardial fibrosis is one of the major consequences of progressive CKD, as it may lead to reentry arrhythmias and long-term myocardial dysfunction predisposing to sudden death and/or congestive heart failure. Subclinical myocardial fibrosis, with a potential key role in the development of uraemic cardiac disease, can be measured and characterised by appropriate cardiac magnetic resonance (CMR) techniques. Fibrosis detection was initially based on the contrast agent gadolinium, due to the superiority in sensitivity and accuracy of contrast-based methods in fibrosis assessment relative to native techniques. However, the severe consequences of gadolinium administration in uraemia (nephrogenic systemic fibrosis) have forced practitioners to re-evaluate the methodology. In the present overview, we review the possible contrast-based and contrast agent-free CMR techniques, including native T1 relaxation time, extracellular volume and global longitudinal strain measurement. The review also summarises their potential clinical relevance in CKD patients based on recently published studies.
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http://dx.doi.org/10.1159/000487367DOI Listing
September 2018

Use of subcutaneous treprostinil in pediatric pulmonary arterial hypertension-Bridge-to-transplant or long-term treatment?

Pediatr Transplant 2018 03 19;22(2). Epub 2017 Dec 19.

Pediatric Heart Center, Gottsegen György National Institute of Cardiology, Budapest, Hungary.

PAH is a progressive life-threatening disease in children. While parenteral prostacyclin therapy improves survival in patients with severe PAH, central line-related complications are common. Our aim was to assess the efficacy, safety, and tolerability of subcutaneous treprostinil treatment in pediatric PAH patients. Eight patients were treated with subcutaneous treprostinil at the Pediatric Heart Center Budapest. Indications for subcutaneous treprostinil therapy were clinical worsening and/or echocardiographic progression or switch from intravenous to subcutaneous therapy. Following treprostinil initiation, clinical status improved or did not change in four of eight patients. Two patients were lost early during treprostinil therapy, parenteral treprostinil as a rescue therapy being insufficient in these cases. The final dose in long-term treated patients was between 60 and 100 ng/kg/min. Aside from thrombocytopenia, other severe side effects were not observed. Potts shunt was performed as palliative treatment in two cases. Three patients had successful lung transplantation, and one died while on the waiting list. Long-term subcutaneous treprostinil could be a safe and well-tolerated therapy in children with severe PAH even at higher doses. It may serve as an alternative to intravenous prostacyclin treatment allowing to avoid the potential complications of permanent central line placement.
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http://dx.doi.org/10.1111/petr.13106DOI Listing
March 2018

Microarray Analysis Reveals Increased Expression of Matrix Metalloproteases and Cytokines of Interleukin-20 Subfamily in the Kidneys of Neonate Rats Underwent Unilateral Ureteral Obstruction: A Potential Role of IL-24 in the Regulation of Inflammation and Tissue Remodeling.

Kidney Blood Press Res 2017 28;42(1):16-32. Epub 2017 Feb 28.

MTA-SE, Pediatrics and Nephrology Research Group, Budapest, Hungary.

Background/aims: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms.

Methods: To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro.

Results: Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-β treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells.

Conclusions: This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.
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http://dx.doi.org/10.1159/000464317DOI Listing
March 2018

Subclinical cardiovascular changes in pediatric solid organ transplant recipients.

Pediatr Transplant 2016 Jun 28;20(4):482-4. Epub 2016 Apr 28.

Gottsegen György National Institute of Cardiology, Budapest, Hungary.

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http://dx.doi.org/10.1111/petr.12718DOI Listing
June 2016

Bone metabolism and arterial stiffness after renal transplantation.

Kidney Blood Press Res 2014 28;39(6):507-15. Epub 2014 Nov 28.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Background/aims: To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial.

Methods: Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx).

Results: Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r = -0.35; r = -0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of <24 months, PWV was correlated with BALP and beta-crosslaps (r=0.53; r = 0.69 respectively) while in the ≥24 months group, PWV was correlated with cholesterol (r=0.38).

Conclusions: Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation.
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http://dx.doi.org/10.1159/000368461DOI Listing
September 2015

[Ultrasound examination in childhood: new perspectives].

Authors:
Éva Kis

Orv Hetil 2014 Jan;155(4):132-40

Semmelweis Egyetem, Általános Orvostudományi Kar I. Gyermekgyógyászati Klinika Budapest Bókay J. u. 53. 1083.

Everyday use of the modern imaging techniques such as CT, MRI, isotope, PET/CT decreased the reputation and importance of ultrasound. In some cases, ultrasound is only the first exploratory imaging method. Using the latest multi-slice CT, imaging can be performed in seconds, which led to a dramatic increase in the number of CT exams. However, this also means a significant radiation exposure to children, while US still harmless in this regard. In addition, significant progress has been made in ultrasound technology in recent years, which led an improvement in image quality. Children are ideal subjects for US examination as they usually have smaller weight with less body fat. Thus, ultrasound examination is easy to perform with a high frequency transducer resulting in much more detailed and higher resolution than in adults. With adequate equipment and experienced examiner in pediatric radiology, almost all parts of the body can be examined, making this technique as the first (sometimes together with X-ray) and, in most cases, the ultimate imaging exam for the diagnosis. This article will discuss the possibilities where ultrasound performed with a modern device is sufficient for an accurate diagnosis.
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http://dx.doi.org/10.1556/OH.2014.29813DOI Listing
January 2014

Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1.

Hypertension 2014 Jan 14;63(1):74-9. Epub 2013 Oct 14.

Washington University School of Medicine, 660 S Euclid, Campus Box 8208, St. Louis, MO 63110.

Williams syndrome is caused by the deletion of 26 to 28 genes, including elastin, on human chromosome 7. Elastin insufficiency leads to the cardiovascular hallmarks of this condition, namely focal stenosis and hypertension. Extrapolation from the Eln(+/-) mouse suggests that affected people may also have stiff vasculature, a risk factor for stroke, myocardial infarction, and cardiac death. NCF1, one of the variably deleted Williams genes, is a component of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex and is involved in the generation of oxidative stress, making it an interesting candidate modifier for vascular stiffness. Using a case-control design, vascular stiffness was evaluated by pulse wave velocity in 77 Williams cases and matched controls. Cases had stiffer conducting vessels than controls (P<0.001), with increased stiffness observed in even the youngest children with Williams syndrome. Pulse wave velocity increased with age at comparable rates in cases and controls, and although the degree of vascular stiffness varied, it was seen in both hypertensive and normotensive Williams participants. Use of antihypertensive medication and extension of the Williams deletion to include NCF1 were associated with protection from vascular stiffness. These findings demonstrate that vascular stiffness is a primary vascular phenotype in Williams syndrome and that treatment with antihypertensives or agents inhibiting oxidative stress may be important in managing patients with this condition, potentially even those who are not overtly hypertensive.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.02087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932371PMC
January 2014

Ambulatory arterial stiffness index in children after kidney transplantation.

Pediatr Transplant 2013 Nov 16;17(7):598-604. Epub 2013 Jul 16.

1st Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Given the increase in CV morbidity after RTx and the scarcity of CV events in pediatrics, surrogate markers should be assessed to characterize CV damage in this population. AASI is a marker of arterial stiffness in adults, predicting cardio- and cerebrovascular morbidity. Our aim was to assess the determinants of AASI in RTx children (n = 54, 15.5 ± 3.5 yr) and to examine its relationship to central PWV. AASI was calculated from 24 h ABPM. PWV was determined by applanation tonometry, body composition by multifrequency bioimpedance measurement. The dipping state, volume overload, and time on dialysis were the main predictors of AASI (p < 0.05). Children with established HT (n = 34) had increased AASI, extracellular body water, and BNP (p < 0.05). In contrast to AASI, PWV did not differ between HT and normotensive RTx patient groups. There was no correlation between AASI and PWV. PWV was increased in children who spent more than one yr on dialysis prior to RTx. In conclusion, increased AASI in HT RTx children better characterizes the actual volume- and pressure-dependent arterial rigidity rather than long-term morphological changes in large arteries as reflected by PWV.
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http://dx.doi.org/10.1111/petr.12123DOI Listing
November 2013

Cardiovascular risk assessment in children with chronic kidney disease.

Pediatr Nephrol 2013 Jun 16;28(6):875-84. Epub 2012 Oct 16.

Renal Unit, Great Ormond Street Hospital for Children, London, UK.

Chronic kidney disease (CKD) is a major factor contributing to cardiovascular (CV) morbidity and mortality with the highest risk in patients on dialysis. An estimation of CV risk is important not only to identify potential modifiable risk factors but also to evaluate the effect of treatments aimed to reduce the risk. Non-invasive methods of measuring vascular changes and circulating biomarkers are available to assess the presence and severity of cardiovascular damage. These include measures of structural (carotid intima-media thickness and coronary artery calcification score) and functional (aortic pulse wave velocity, 24-h ambulatory blood pressure monitoring, ambulatory arterial stiffness index, heart rate variability and flow-mediated dilatation) changes in the vessel wall. In addition, a number of circulating biomarkers of vascular damage and its progression have been studied. Many of these tests are well validated as surrogate markers of future cardiovascular events and death in adult CKD patients, but need technical adaptation, standardization and validation for use in children. With our current state of knowledge, these are best reserved for research studies and scarce clinical resources may be better utilized for preventative strategies to reduce the modifiable risk factors for calcification from early CKD stages.
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http://dx.doi.org/10.1007/s00467-012-2325-3DOI Listing
June 2013

Cardiovascular risk assessment in children following kidney transplantation.

Pediatr Transplant 2012 Sep 14;16(6):564-76. Epub 2012 Jun 14.

First Department of Pediatrics, Semmelweis University, Budapest, Hungary.

CV diseases are the leading cause of death among patients with ESRD. RTX decreases the CV risk; however, it still remains definitely higher than that of the general population. Large multicenter and longitudinal studies are difficult to perform and hard end-points of CV events are usually missing among pediatric population. Thus, appropriate estimation of CV risk is of crucial importance to define the potential hazards and to evaluate the effect of treatments aimed to reduce the risk. A number of validated non-invasive methods are available to assess the extent of CV damage in adults, such as calcification scores, cIMT, aPWV, 24-h ABPM, AASI, and HRV; however, they need adaptation, standardization, and validation in pediatric studies. cIMT and PWV are the most promising methods, as pediatric normative values are already present. The up-to-date treatment of ESRD aims not only to save life, but to offer the patient a life expectancy approaching that of the healthy population and to ensure a reasonable quality of life.
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http://dx.doi.org/10.1111/j.1399-3046.2012.01730.xDOI Listing
September 2012

Immunosuppression with 4SC-101, a novel inhibitor of dihydroorotate dehydrogenase, in a rat model of renal transplantation.

Transplantation 2012 Jun;93(11):1101-7

Department of Nephrology, Klinikum rechts der Isar, Munich, Germany.

Background: 4SC-101 is a novel dihydroorotate dehydrogenase inhibitor and a blocker of interleukin (IL)-17 secretion with beneficial effects in experimental lupus and inflammatory bowel disease. Its immunomodulatory effect on acute kidney rejection is not known; therefore, in this study, the impact of 4SC-101 was examined in a rat model of acute kidney rejection.

Methods: The kidneys of Brown-Norway rats were orthotopically transplanted into bilaterally nephrectomized Lewis recipients. Allograft recipients were administered with 4SC-101 at dosages of 4, 20, or 60 mg/kg per day, and survival was assessed. In the second setting, the animals were harvested 3 or 5 days after transplantation (Tx), and graft histologic diagnosis was determined. The effects of 4SC-101 on impaired renal function were examined in a model of 5/6 nephrectomy in Lewis rats.

Results: The recipients treated with 20-mg/kg 4SC-101 showed prolonged survival compared with placebo-treated animals (mean±SEM, 24±9.3 vs. 5.4±3 days), paralleled by less severe histologic features of acute kidney rejection such as interstitial/perivascular infiltration and tubulitis 3 and 5 days after Tx, and a lower level of IL-17 messenger RNA 5 days after Tx compared with the placebo-treated animals. In the 5/6 nephrectomy model, 20-mg/kg 4SC-101 reduced proteinuria, glomerulosclerosis, and fibrosis with decreased IL-17 messenger RNA expression.

Conclusions: 4SC-101 prolongs survival after Tx, paralleled by amelioration of histologic signs of acute rejection. Furthermore, it showed no worsening effects on kidney function in a remnant kidney model and even slowed the progression of proteinuria and kidney fibrosis. Therefore, 4SC-101 might be a promising pharmaceutical agent in Tx medicine for further investigations.
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http://dx.doi.org/10.1097/TP.0b013e31824fd861DOI Listing
June 2012

Measurement of pulse wave velocity in children and young adults: a comparative study using three different devices.

Hypertens Res 2011 Nov 28;34(11):1197-202. Epub 2011 Jul 28.

First Department of Pediatrics, Semmelweis University, Budapest, Hungary.

To estimate the value of pulse wave velocity (PWV) in pediatric cardiovascular disease, prospective studies are needed. Various instruments based on different measurement principles are proposed for use in children, hence the need to test the comparability of these devices in this younger population. The objective of this study was to compare PWV measured by oscillometry (Vicorder (VIC)) with the gold standard of applanation tonometry (PulsePen (PP), Sphygmocor (SC)). PWV was measured in 98 children and young adults (age: 16.7(6.3-26.6) years (median(range)) with the above three devices at the same visit under standardized conditions. Mean PWV measured by VIC was significantly lower than that measured by SC and PP. There was no difference following path length correction of the VIC measurement (using the distance between the jugular notch and the center of the femoral cuff), (PP: 6.12(1.00), SC: 5.94(0.91), VIC: 6.14(0.75) m s(-1)). Velocities measured by the three devices showed highly significant correlations. Bland-Altman analysis revealed excellent concordance between all three devices, however, there was a small but significant proportional error in the VIC measurements showing a trend toward lower PWV measured by VIC at higher PWV values. Our study provides data on the three most frequently used instruments in pediatrics. Following path length correction of the VIC, all three devices provided comparable results. Thus, our work allows extrapolating data between previously established normal PWV values for children and forthcoming studies using these instruments to assess children at long-term risk of cardiovascular disease. The small proportional error of VIC needs additional technical development to improve the accuracy of the measurements.
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http://dx.doi.org/10.1038/hr.2011.103DOI Listing
November 2011

Voiding urosonography with second-generation contrast agent versus voiding cystourethrography.

Pediatr Nephrol 2010 Nov 5;25(11):2289-93. Epub 2010 Aug 5.

1st Department of Pediatrics, Pediatric Radiology Unit, Semmelweis Medical University, 53-54 Str. János Bókay, Budapest, Hungary.

Contrast-enhanced voiding urosonography (VUS) is becoming more widely used for the diagnosis of vesicoureteric reflux (VUR). The purpose of this study was to evaluate the sensitivity of VUS using a second-generation ultrasound (US) contrast agent and compare it with standard fluoroscopic voiding cystourethrography (VCUG). A total of 183 children with 366 kidney-ureter units (KUUs) underwent VUS and VCUG in the same session with the same catheterization. VUS was performed after intravesical administration of 1 ml of a second-generation ultrasound contrast agent (UCA; SonoVue, Bracco, Italy). VUR was detected in 140 out of 366 cases (38%); in 89 (24.3%) by both methods, in 37 (10.1%) by VUS only, and in 14 (3.8%) by VCUG only. Although there was considerable agreement in the diagnosis of VUR by VUS and VCUG (κ=0.68, standard error [κ]=0.04), the difference in the detection rate of reflux between VUS and VCUG was significant (p<0.00001). The grade of VUR detected with VUS showed moderate agreement with grading by VCUG. Our findings suggest that contrast-enhanced harmonic VUS using a second-generation contrast agent is superior to VCUG in the detection and grading of VUR, and it should be the method of choice for this clinical indication.
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http://dx.doi.org/10.1007/s00467-010-1618-7DOI Listing
November 2010

Reference values of pulse wave velocity in healthy children and teenagers.

Hypertension 2010 Aug 21;56(2):217-24. Epub 2010 Jun 21.

First Department of Pediatrics, Semmelweis University, Budapest, Budapest, Hungary.

Carotid-femoral pulse wave velocity is an established method for characterizing aortic stiffness, an individual predictor of cardiovascular mortality in adults. Normal pulse wave velocity values for the pediatric population derived from a large data collection have yet to be available. The aim of this study was to create a reference database and to characterize the factors determining pulse wave velocity in children and teenagers. Carotid-femoral pulse wave velocity was measured by applanation tonometry. Reference tables from pulse wave velocities obtained in 1008 healthy subjects (aged between 6 and 20 years; 495 males) were generated using a maximum-likelihood curve-fitting technique for calculating SD scores in accordance with the skewed distribution of the raw data. Effects of sex, age, height, weight, blood pressure, and heart rate on pulse wave velocity were assessed. Sex-specific reference tables and curves for age and height are presented. Pulse wave velocity correlated positively (P<0.001) with age, height, weight, and blood pressure while correlating negatively with heart rate. After multiple regression analysis, age, height, and blood pressure remained major predictors of pulse wave velocity. This study, involving >1000 children, is the first to provide reference values for pulse wave velocity in children and teenagers, thereby constituting a suitable tool for longitudinal clinical studies assessing subgroups of children who are at long-term risk of cardiovascular disease.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.110.152686DOI Listing
August 2010

Captopril-enhanced renal scintigraphy in the diagnosis of pediatric hypertension.

Pediatr Nephrol 2010 Feb 20;25(2):185-9. Epub 2009 Oct 20.

Pediatric Nephrology, First Department of Pediatrics, Semmelweis University, Bókay János u 53-54, Budapest 1083, Hungary.

Hypertension in childhood is no longer a rare condition mainly secondary to renal, or renovascular diseases, as a growing proportion of children are obese and hypertensive, with the phenotype of metabolic syndrome. Thus, we need to reconsider our practice in the examination of the hypertensive child and redefine the place of non-invasive methods for screening of renovascular hypertension, and specifically, to evaluate the value of captopril-enhanced renal scintigraphy at the two ends of the palette: the obese child with hypertension and the severely hypertensive prepubertal child. Renal artery stenosis in children is mainly due to fibromuscular dysplasia and stenoses associated with syndromes involving single or multiple smaller branch vessels. This explains the low specificity and sensitivity of the color-Doppler ultrasound method and captopril renal scintigraphy. Even the more sophisticated computed tomography (CT) and magnetic resonance imaging (MRI) angiographic techniques are, at present, not sensitive enough to exclude stenoses of the small branches definitely. Thus, children in whom there is a strong suggestion of renovascular hypertension should undergo angiography with a view to endovascular treatment, as non-invasive imaging has no significant benefit and might lead to a delay in treatment. In the cases when the probability of renovascular disease is moderate a basic assessment of renal function and structure is sufficient. In the neonate, catheter-associated thromboembolic disease is among the most common causes hypertension. It should be controlled medically until the patient is old enough to undergo angiography and angioplasty successfully. Thus, in this age group, there is a place for functional imaging with renal sonography and angiotensin-converting enzyme inhibitor (ACEI) renography to detect hemodynamically significant renovascular disease, with the limitations mentioned above. However, the rapid technical evolution of non-invasive methods requires periodic re-consideration of the actual standpoints.
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http://dx.doi.org/10.1007/s00467-009-1321-8DOI Listing
February 2010

Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure.

Pediatr Nephrol 2009 Dec;24(12):2413-20

First Department of Pediatrics, Semmelweis University, Budapest Bókay János u. 53-54, 1083, Hungary.

Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast increases via vascular calcification and can be characterized by pulse wave velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (beta)]. Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone markers were analyzed. Ca x P/fetuin-A ratio was calculated to characterize the balance of calcification and inhibition. Cumulative dose of calcitriol was also assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone markers and Ca x P/ fetuin-A of D were significantly higher than those of Tx and controls. In D PWV/h correlated with Ca x P/fetuin-A and BALP (r=0.8; p=0.005, r=0.6, p=0.05, respectively); BALP correlated with Ca x P/fetuin-A (r=0.7, p=0.01). In Tx, there was a correlation between calcitriol administered before transplantation and PWV/h (r=0.5, p=0.04). Increased bone turnover was coupled with an increased potential of calcium-phosphate precipitation, as shown by the increased Ca x P/fetuin-A. It might explain the connection between disturbed mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow-up studies are needed.
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http://dx.doi.org/10.1007/s00467-009-1292-9DOI Listing
December 2009

Pulse wave velocity in children following renal transplantation.

Nephrol Dial Transplant 2009 Jan 5;24(1):309-15. Epub 2008 Sep 5.

Department of Pediatrics, Semmelweis University, Budapest, Hungary.

Background: Arterial stiffness (ASt) increases with age, a process accelerated by uraemia and reversed by transplantation (Tx). Increased ASt results in an elevated pulse wave velocity (PWV).

Methods: To compare the PWV of Tx patients (n = 25, age = 15.1/95% CI = 13.5-16.7/year) and healthy controls, three control groups were formed: matched for age (A), for height and weight (H/W) and for age and height (A/H), respectively. To avoid bias from the growth deficit of Tx, firstly Z-scores of PWV were calculated (PWV-Z). Second, the PWV/height (PWV/h) ratio was assessed. Pre-Tx serum Ca, P, PTH and the cumulative dose of calcitriol (cCTL) were also analysed. Finally, Tx patients were compared to ESRD patients (n = 11). PWV was measured by applanation tonometry.

Results: Tx were smaller than A and older than H/W. The PWV of Tx differed only from H/W and A/H. PWV-Z and PWV/h of Tx were increased compared to all control groups. They correlated with the CaxP and cCTL before Tx and were independent of age. Patients with creatinine clearance >90 ml/min/1.73 m(2) or <1 year on dialysis had lower PWV-Z and PWV/h than ESRD.

Conclusion: Controls that matched for both age and height should be used to assess PWV in children with growth failure. PWV-Z is a universal age-independent parameter of PWV in cases of growth retardation; PWV/h is a simple alternative of PWV-Z. CaxP and cCTL are major determinants of ASt after Tx. PWV may be reduced after Tx suggesting that the uraemia-induced cardiovascular changes might be reversible.
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http://dx.doi.org/10.1093/ndt/gfn494DOI Listing
January 2009

[Vena portae obstruction as a cause of portal hypertension in a child with Turner syndrome].

Orv Hetil 2008 Jun;149(23):1079-84

Semmelweis Egyetem, Altalános Orvostudományi Kar I. Gyermekgyógyászati Klinika Budapest Bókay u. 53. 1083.

Cardiovascular and renal malformations are well-known in Turner syndrome. However, gastrointestinal bleeding is less frequent. The possible etiologies of gastrointestinal bleeding in Turner syndrome are intestinal teleangiectasia, inflammatory bowel disease and portal hypertension. The authors report a 3-year-old girl with Turner syndrome who presented with severe gastrointestinal bleeding requiring transfusion. The radiological examination indicated prehepatic portal hypertension as a reason for haematochezia. The liver biopsy demonstrated the anomaly of intrahepatic arteries and veins. In this report we describe a case of congenital portal vein obstruction and we reviewed liver abnormalities associated with Turner syndrome and causes of obstruction of vena portae in childhood.
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http://dx.doi.org/10.1556/OH.2008.28341DOI Listing
June 2008

Pulse wave velocity in end-stage renal disease: influence of age and body dimensions.

Pediatr Res 2008 Jan;63(1):95-8

First Department of Pediatrics, Semmelweis University, Budapest, Hungary, 1083.

Arterial stiffness increases with age. This process is accelerated by end-stage renal disease (ESRD). Pulse wave velocity (PWV) increases with arterial stiffness. In this study, PWV of 133 healthy individuals (6-23 y of age) and 11 patients on dialysis was measured to establish the normal values of PWV and to compare them with those in ESRD. Age-matched (A-C) and height- and weight-matched (H/W-C) control groups were used. Thereafter, PWV was indexed to height and the data were reevaluated. The role of the risk factors including serum calcium, phosphate, parathyroid hormone (PTH), and the time on dialysis was analyzed using a score system. PWV correlated with age, weight, height, blood pressure, and heart rate. ESRD patients were smaller than A-C and older than H/W-C. PWV of patients with ESRD did not differ from A-C; however, it was elevated in comparison to H/W-C. In both healthy and ESRD patients, the PWV/height ratio was independent of age. PWV/height was increased in ESRD. There was a correlation between PWV/height and the risk factor score. Controls matched for height and weight or PWV/height should be used in cases of growth failure. A number of risk factors responsible for increased arterial stiffness are present in ESRD.
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http://dx.doi.org/10.1203/PDR.0b013e31815b47ffDOI Listing
January 2008

[Osteopenia of prematurity].

Orv Hetil 2005 Dec;146(49):2491-7

MTA Semmelweis Egyetem, Gyermekgyógyászati es Nefrológiai Kutatócsoport, I. Gyermekgyógyászati Klinika, Budapest.

The survival rate of premature infants has been significantly increased during the last decades. As a consequence, the problem of less imminent, slowly progressing, but also important disorders such as osteopenia of prematurity has been emerging. The diagnosis of osteopenia of prematurity is based evidence for less bone mineral density compared to fetuses or infants at the same gestational age in the absence of laboratory parameters and/or clinical signs for rachitis or other metabolic bone disease. The incidence of osteopenia among infants born before 28 weeks of gestational age are as high as 30%. The aim of this paper is to review the information regarding the prevention and treatment of osteopenia of prematurity and to summarize the preventive measures to avoid fractures or bone deformations and to achieve the genetically determined peak bone mass. The latter is essential for the prevention of osteoporosis in adulthood, a significant problem of public health.
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December 2005

Myoelectrical activity of the stomach after surgical correction of esophageal atresia.

J Pediatr Surg 2005 Nov;40(11):1732-6

1st Department of Pediatrics, Semmelweis University, Budapest 1083, Hungary.

Aim: The aim of this study was to investigate the motor activity in the stomach of infants with repaired esophageal atresia (EA).

Method: Gastric myoelectrical activity was investigated by cutaneous electrogastrography in 15 infants after the surgical correction of EA. Ten infants with no gastrointestinal upset served as controls. Studies were done before and after a milk feed. The pH of the lower esophagus was measured for 24 hours to assess the gastroesophageal reflux (GER) in the infants with repaired EA.

Results: After feeding, a significant increase in bradygastria and decrease in tachygastria were observed as compared with the preprandial period. Compared with healthy infants, the electrogram showed pathological patterns in 73.3% (11/15) of EA patients. Twelve of 15 EA patients showed some clinical sign of GER, and 60% of the EA patients proved to be GER-positive on esophageal pH monitoring. There was no difference in the distribution of gastric myoelectrical waves between the GER-positive and GER-negative EA patients either before or after meal.

Conclusion: Cutaneous electrogastrography is a noninvasive, harmless method for obtaining indirect information about the motor function of the stomach. The abnormal changes in physiological gastric myoelectrical activity in EA patients can serve as markers of disturbed neuromuscular function and can play a role in the pathogenesis of feeding disturbances after operative correction of EA. Gastroesophageal reflux, which often occurs after surgical repair of EA, seems to be connected not only with disordered gastric myoelectric activity, but also probably with other factors such as artificially straightened esophagogastric angle or brachyesophagus.
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http://dx.doi.org/10.1016/j.jpedsurg.2005.07.031DOI Listing
November 2005

[Infantile acute lobar nephritis].

Orv Hetil 2002 Apr;143(15):779-81

Semmelweis Egyetem, Budapest, Altalános Orvostudományi Kar, I. sz. Gyermekklinika.

Introduction: Acute lobar nephronia is a focal interstitial inflammation of the kidney healing well on conservative therapy.

Objective: Authors call attention on this rare pathological entity and emphasize the role of the imaging modalities in making the diagnosis. Short literature review is also given.

Patient And Methods: An 11 months old babyboy presented with febrile seizure and palpable right flank mass. Abdominal sonography and CT were done.

Results: Urine analysis gave evidence of upper urinary tract infection. Hyperechogenic solid mass in the right kidney was seen on sonography. Diagnosis of infection suspected on sonography has been confirmed by abdominal CT scan and possibility of tumor has been ruled out. Acute lobar nephronia was diagnosed and the patient has been treated successfully with antibiotics.

Conclusion: Acute lobar nephronia may mimic both abscess and tumor. Differential diagnosis is very important because treatment of acute lobar nephronia is nonsurgical.
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April 2002