Examination of early indicators of cardiovascular damage in children with idiopathic nephrotic syndrome

Nastanak ateroskleroze kod dece sa idiopatskim nefrotskim sindromom nije dovoljno ispitan. Pacijenti sa kortikosteroid zavisnim i kortikosteroid rezistentnim nefrotskim sindromom su u riziku za razvoj kardiovaskularne bolesti shodno broju relapsa i dužini primene kortikosteroidne terapije. Nastanak kardiovaskularne bolesti može se objasniti metaboličkim poremećajima koji se javljalju u aktivnoj fazi bolesti (dislipoproteinemija, hipoalbuminemija, hiperkoagulabilnost, povećan oksidativni stres), kao i komplikacijama usled dugotrajne steroidne terapije (gojaznost, hipertenzija, poremećaj metabolizma lipida, poremećaj metabolizma glukoze). Merenje debljine intime i medije karotidnih arterija je pouzdan i često primenjivan metod za određivanje vaskularne bolesti, koja se odlikuje fibrozom intime i kalcifikacijom medije. Masa leve komore je značajno veća kod dece sa nefrotskim sindromom, a naročito ako imaju arterijsku hipertenziju, povećanu krutost karotidnih arterija, ili su u ranoj fazi hronične bolesti bubrega. Cilj: Ispitivanje faktora za nastanak kardiovaskularne bolesti kod pacijenata sa kortikosteroid zavisnim i kortikosteroid rezistentnim nefrotskim sindromom i uporediti sa kontrolnom grupom zdrave dece. Ciljevi istraživanja su: opisati i uporediti kliničke i biohemijske karakteristike ispitivanih grupa; ispitati značajnost razlike debljine intime i medije karotidnih arterija; ispitati povezanost kliničkih i biohemijskih parametara sa debljinom intime i medije karotidnih arterije kod dece sa idiopatskim nefrotskim sindromom; ispitati povezanost kliničkih i biohemijskih parametara sa indeksom mase leve komore i globalnom longitudinalnom napetošću (eng. Global longitudinal strain-GLS) kod dece sa idiopatskim nefrotskim sindromom; ispitati potencijalne prediktore (antropometrijski i biohemijski parametri, vrednost krvnog pitiska) u odnosu na debljinu intime i medije karotidnih arterija, indeksa mase leve komore i GLS. Metodologija: Studija preseka izvedena je u Institutu za zdravstvenu zaštitu majke i deteta „Dr Vukan Čupić“, uključila je 40 pacijenata sa kortikosteroid zavisnim i kortikosterid rezistentnim nefrotskim sindromom i 20 zdrave dece...The development of atherosclerosis in children with idiopathic nephrotic syndrome has not been sufficiently studied. Patients with corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome are at risk for developing cardiovascular disease according to the number of relapses and the length of corticosteroid therapy. The onset of cardiovascular disease can be explained by metabolic disorders that occur in the active phase of the disease (dyslipoproteinemia, hypoalbuminemia, hypercoagulability, increased oxidative stress), as well as complications due to long-term steroid therapy (obesity, hypertension, metabolic disorders). Measuring the thickness of the intima and media of the carotid arteries is a reliable and often used method for determining vascular disease, which is characterized by fibrosis of the intima and calcification of the media. The mass of the left ventricle is significantly higher in children with nephrotic syndrome, especially if they have arterial hypertension, increased stiffness of the carotid arteries, or are in the early phase of chronic kidney disease. Objective: The aim of this study was to examine the risk factors for cardiovascular disease in children with corticosteroid dependent and corticosteroid resistant nephrotic syndrome and to compare it with the control group of healthy children. In order to achieve the goal of the study, the following research tasks were set: to describe and compare the clinical and biochemical characteristics of the study groups; examine the significance of the difference in the thickness of the intima and the media of the carotid arteries; to examine the relationship between clinical and biochemical parameters with the thickness of the intima and media of the carotid arteries in children with idiopathic nephrotic syndrome; examine the relationship between clinical and biochemical parameters with left ventricular mass index and global longitudinal strain (GLS) in children with idiopathic nephrotic syndrome; examine potential predictors (anthropometric and biochemical parameters, blood pressure value) in relation to the thickness of the intima and media of the carotid arteries, left ventricular mass index and global longitudinal strain..

Alterations of HDL Particles in Children with End-Stage Renal Disease

Background: Unfavorable lipid profile presents one of most important risk factor for cardiovascular disease in renal pathology. Myeloperoxidase (MPO) as enzyme which oxidizes lipoproteins and paraoxonase1 (PON1) as anti-oxidative enzyme have been involved in pathogenesis of cardiovascular disease. In the present study we sought to assess oxidative stress status, lipoprotein subclasses distribution as well as functionality of high density lipoprotein (HDL) trough MPO/PON1 ratio in children with chronic kidney disease (CKD) and children after renal transplantation. Methods: PON1 activity and oxidative stress parameters were measured spectrophotometrically, while MPO concentration was determined using immunoassay. Separation of lipoprotein subclasses was performed by vertical gradient gel electrophoresis in 19 children with different stage of CKD and 19 post-transplantation patients (PT). Results: CKD patients had increased MPO/PON1 ratio and higher prevalence of smaller HDL subclasses when compared to PT subjects. Also, there was a significant positive correlation between MPO level and MPO/PON1 ratio with relative proportion of smaller HDL subclasses. Conclusions: Children with CKD have impaired HDL distribution that is improved after kidney transplantation. Since that measurement of HDL distribution and functionality arenot routinely available, MPO/PON1 ratio may be useful marker that could provide necessary information

Pedijatrijski nefrotski sindrom: međusobna interakcija oksidativnog stresa i inflamacije

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (- SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflam- matory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the dis- ease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (r s =0.42, p=0.027 and r s =0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxi- dant capacity may contribute to nephrotic syndrome devel- opment. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflam- mation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.Uvod: Patofiziološki mehanizmi ključni u razvoju nefrotskog sindroma (NS) u pedijatrijskoj populaciji još uvek nisu u potpunosti razjašnjeni. Ova studija ima za cilj proučavanje sinergističkog delovanja oksidativnog stresa i inflamacije u patogenezi NS. Takođe, jedan od ciljeva ove studije je i ispitivanje veze hipertenzije sa stepenom oksidativnog stresa i inflama - cije kod pacijenata u akutnoj fazi bolesti. Metode: U studiju je uključeno 33 dece sa NS uzrasta od 2 do 9 godina. Uzorci krvi su prikupljeni tokom akutne faze i remisije. Od parametara oksidativnog statusa određivani su: totalni oksidativni status (TOS), uznapredovali proizvodi oksidacije proteina (AOPP), balans prooksidans-antioksidans (PAB), sulfhidrilne grupe (-SH), paraoksonaza 1 (PON1) i ukupan antioksidativni status (TAS) u serumu su mereni spektrofometrijski, a od parametara inflamacije su pentraksin 3 (PTX3), leptin, ligand programirane smrti ćelije 1 (PD-L1) i E-kadherin određivani metodom enzimskog imunosorbentnog testa (ELISA). Rezultati: Pacijenti sa NS i hipertenzijom imali su značajno više nivoe AOPP i TOS (p=0.029 i p=0.003, respektivno). U akutnoj fazi bolesti su uočene nižu aktivnost -SH i PON1 u poređenju sa remisijom (p<0.001, za oba). Nivoi PTX 3 su bili viši, dok su nivoi leptina bili niži tokom akutne faze (p<0.001, za oba). PTX 3 je korelirao sa AOPP i TAS u akutnoj fazi, ali ne i u remisiji (rs=0.42, p=0.027 i rs=0.43, p=0.025,respektivno). U akutnooj fazi utvrđena je negativna korelacija između AOPP i leptina, koja je nestala u remisiji (rs=-0.42, p=0.028). Zaključak: Rezultati ove studije ukazuju da hipertenzija utiče na markere oksidativnog stresa, a smanjeni antioksidativni kapacitet može doprineti razvoju NS. PTX3 se pojavljuje kao potencijalni marker aktivnosti bolesti, što ukazuje na dinamičku vezu između inflamacije i oksidativnog stresa. Leptin može igrati ulogu u oksidativnom stresu u NS

Association of Myeloperoxidase and the Atherogenic Index of Plasma in Children with End-Stage Renal Disease

Background: The aim of this study was to explore oxidative stress status, especially the enzyme myeloperoxidase in children with end-stage renal disease. Also, we investigated possible associations between the atherogenic index of plasma and these parameters. Methods: Lipid status parameters, oxidative stress status parameters, and myeloperoxidase concentration were measured in the sera of 20 children in the last stage of chronic renal disease (ESRD) and 35 healthy children of matching age and sex. The Atherogenic Index of Plasma (AIP) was calculated according to the appropriate equation. Results: We did not find any significant differences in myeloperoxidase concentrations between the investigated groups (p = 0.394). Oxidative stress parameters were, however, significantly higher in the patient group (p lt 0.001), as well as the atherogenic index of plasma (p lt 0.001). Myelo per oxidase concentration and advanced oxidation protein product (AOPP) concentration were independently associated with increased AIP in the patient group (p lt 0.05). Conclusions: Changes in AIP in children with ERSD are associated with the oxidative stress status and myeloper oxidase concentration

Associations of Apgar score and size at birth with lipoprotein subclasses in juvenile obesity

N Background/aim: Juvenile obesity is associated with several metabolic abnormalities, one of them being atherogenic dyslipidemia. Suboptimal fetal growth is associated with obesity risk in childhood, but also with increased rate of metabolic diseases in later life. This study investigated associations of neonatal data (Apgar score, birth weight and birth length) with low-density lipoprotein and high-density lipoprotein (LDL and HDL) subclasses in a group of obese children, as well as a possible impact of breastfeeding duration on obesity-associated lipoprotein subclasses distributions. Materials and methods: We included 42 obese children, aged 14.2 +/- 2.1 years. LDL and HDL subfractions were separated by gradient gel electrophoresis and biochemical parameters were assessed by routine methods. Results: Compared with obese children with Apgar >= 9, the group with Apgar lt 9 had significantly higher percentages of small, dense LDL particles (P lt 0.05), due to reduced LDL I (P lt 0.01) and increased LDL III subclasses (P lt 0.05). Birth weight was positively associated with the proportions of LDL I particles (P lt 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P lt 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P lt 0.01) and lower proportion of HDL 2a particles (P lt 0.05) than their >= 3 months breastfed peers. Conclusion: The results showed significant associations of neonatal characteristics with LDL and HDL particle distributions in obese children. In addition, our results point toward positive aspects of longer breastfeeding duration on lipoprotein particle distributions in obese children

Rezistin, inflamacija i dislipidemija kod gojazne dece i adolescenata

Introduction: Childhood obesity is related to cardiovascular diseases and diabetes mellitus type 2 in later life. Resistin, an adipokine primarily secreted by monocytes and tissue macrophages in humans, is considered to be associated with these conditions. The Aim: To examine the correlations between resistin concentration and anthropometric parameters, lipid status, inflammatory markers and parameters of insulin resistance in obese children and adolescents. Material and Methods: The study included 66 patients (40 boys, 26 girls), which underwent anthropometric measuring and laboratory testing (glucose level, total cholesterol, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), triglycerides, uric acid, high-sensitivity C-reactive protein (hsCRP) and glycosylated hemoglobin (HbA1c). Insulin resistance was estimated with HOMA-IR (homeostasis model assessment of insulin resistance). Results: We determined that 63.3% of our patients had dyslipidemia, while hsCRP and uric acid levels suggested an ongoing inflammation. We established that there was a correlation between resistin concentration and waist to hip ratio (WHR) (r=0.294, p lt 0.05), as well as between resistin concentration and HOMA-IR (r=0.293, p lt 0.05). Also, uric acid levels correlated with obesity parameters. While comparing parameters by gender we found a significant difference in height (p lt 0.01), WHR (p lt 0.001), uric acid levels (p lt 0.01) and HOMA-IR (p lt 0.01). Conclusion: Our results show a link between obesity, inflammation and dyslipidemia in children and adolescents. In the future, resistin could become a significant clinical marker for evaluation of cardiometabolic risk.Uvod: Gojaznost u dečjem uzrastu se povezuje sa razvojem kardiovaskularnih bolesti i tipa 2 dijabetes melitusa u kasnijem dobu. Smatra se da je rezistin, adipokin kojeg u humanom organizumu luče monociti i tkivne makrofage, povezan sa ovim poremećajima. Cilj: Ispitati povezanost koncentracije rezistina kod gojazne dece i adolescenata sa antropometrijskim parametrima gojaznosti, lipidnim statusom, inflamatornim markerima i parametrima insulinske rezistencije. Materijal i metode: U istraživanju je učestvovalo 66 ispitanika (40 dečaka, 26 devojčica) kojima su izvršena antropometrijska merenja i laboratorijska ispitivanja (koncentracije glukoze, ukupnog holesterola, holesterola u česticama lipoproteina visoke gustine (eng. high-density lipoprotein, HDL) i niske gustine (eng. low-density lipoprotein, LDL), triglicerida, mokraćne kiseline, visokoosetljivog C-reaktivnog proteina (high-sensitivity C-reactive protein; hsCRP) i glikoziliranog hemoglobina (HbA1c)). Insulinska rezistencija je procenjena na osnovu modela za izračunavanje indeksa insulinske rezistencije (eng. homeostasis model assessment of insulin resistance; HOMA-IR). Rezultati: Kod 63,3% ispitanika utvrdili smo prisutnu dislipidemiju, a dobijene vrednosti hsCRP i mokraćne kiseline ukazuju na prisustvo inflamacije. Utvrdili smo korelaciju između koncentracije rezistina i odnosa obima struka i kukova (r=0,294, p lt 0,05) i između koncentracije rezistina i HOMA-IR (r=0,293, p lt 0,05). Ustanovili smo povezanost koncentracije mokraćne kiseline i parametara gojaznosti. Upoređivanjem parametara između polova, značajna razlika postoji u telesnoj visini (p lt 0,01), odnosu obima struka i kukova (p lt 0,001), mokraćnoj kiselini (p lt 0,01) i HOMA-IR (p lt 0,01). Zaključak: Naši rezultati ukazuju na povezanost gojaznosti, inflamacije i dislipidemije kod dece i adolescenata. Rezistin bi u budućnosti mogao biti značajan za procenu kardiometaboličkog rizika u ovoj populaciji

SuO033EXPLORING THE DIFFERENTIAL MORTALITY RISK IN EUROPEAN CHILDREN WITH END-STAGE RENAL DISEASE - RESULTS FROM THE ESPN/ERA-EDTA REGISTRY

DAB1214 TAXATION THEORY SUP

Examination of early indicators of cardiovascular damage in children with idiopathic nephrotic syndrome

Nastanak ateroskleroze kod dece sa idiopatskim nefrotskim sindromom nije dovoljno ispitan. Pacijenti sa kortikosteroid zavisnim i kortikosteroid rezistentnim nefrotskim sindromom su u riziku za razvoj kardiovaskularne bolesti shodno broju relapsa i dužini primene kortikosteroidne terapije. Nastanak kardiovaskularne bolesti može se objasniti metaboličkim poremećajima koji se javljalju u aktivnoj fazi bolesti (dislipoproteinemija, hipoalbuminemija, hiperkoagulabilnost, povećan oksidativni stres), kao i komplikacijama usled dugotrajne steroidne terapije (gojaznost, hipertenzija, poremećaj metabolizma lipida, poremećaj metabolizma glukoze). Merenje debljine intime i medije karotidnih arterija je pouzdan i često primenjivan metod za određivanje vaskularne bolesti, koja se odlikuje fibrozom intime i kalcifikacijom medije. Masa leve komore je značajno veća kod dece sa nefrotskim sindromom, a naročito ako imaju arterijsku hipertenziju, povećanu krutost karotidnih arterija, ili su u ranoj fazi hronične bolesti bubrega. Cilj: Ispitivanje faktora za nastanak kardiovaskularne bolesti kod pacijenata sa kortikosteroid zavisnim i kortikosteroid rezistentnim nefrotskim sindromom i uporediti sa kontrolnom grupom zdrave dece. Ciljevi istraživanja su: opisati i uporediti kliničke i biohemijske karakteristike ispitivanih grupa; ispitati značajnost razlike debljine intime i medije karotidnih arterija; ispitati povezanost kliničkih i biohemijskih parametara sa debljinom intime i medije karotidnih arterije kod dece sa idiopatskim nefrotskim sindromom; ispitati povezanost kliničkih i biohemijskih parametara sa indeksom mase leve komore i globalnom longitudinalnom napetošću (eng. Global longitudinal strain-GLS) kod dece sa idiopatskim nefrotskim sindromom; ispitati potencijalne prediktore (antropometrijski i biohemijski parametri, vrednost krvnog pitiska) u odnosu na debljinu intime i medije karotidnih arterija, indeksa mase leve komore i GLS. Metodologija: Studija preseka izvedena je u Institutu za zdravstvenu zaštitu majke i deteta „Dr Vukan Čupić“, uključila je 40 pacijenata sa kortikosteroid zavisnim i kortikosterid rezistentnim nefrotskim sindromom i 20 zdrave dece...The development of atherosclerosis in children with idiopathic nephrotic syndrome has not been sufficiently studied. Patients with corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome are at risk for developing cardiovascular disease according to the number of relapses and the length of corticosteroid therapy. The onset of cardiovascular disease can be explained by metabolic disorders that occur in the active phase of the disease (dyslipoproteinemia, hypoalbuminemia, hypercoagulability, increased oxidative stress), as well as complications due to long-term steroid therapy (obesity, hypertension, metabolic disorders). Measuring the thickness of the intima and media of the carotid arteries is a reliable and often used method for determining vascular disease, which is characterized by fibrosis of the intima and calcification of the media. The mass of the left ventricle is significantly higher in children with nephrotic syndrome, especially if they have arterial hypertension, increased stiffness of the carotid arteries, or are in the early phase of chronic kidney disease. Objective: The aim of this study was to examine the risk factors for cardiovascular disease in children with corticosteroid dependent and corticosteroid resistant nephrotic syndrome and to compare it with the control group of healthy children. In order to achieve the goal of the study, the following research tasks were set: to describe and compare the clinical and biochemical characteristics of the study groups; examine the significance of the difference in the thickness of the intima and the media of the carotid arteries; to examine the relationship between clinical and biochemical parameters with the thickness of the intima and media of the carotid arteries in children with idiopathic nephrotic syndrome; examine the relationship between clinical and biochemical parameters with left ventricular mass index and global longitudinal strain (GLS) in children with idiopathic nephrotic syndrome; examine potential predictors (anthropometric and biochemical parameters, blood pressure value) in relation to the thickness of the intima and media of the carotid arteries, left ventricular mass index and global longitudinal strain..

Chronic kidney disease during a 12-year period at tertiary health institution

Introduction. Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in paediatric population. Objective. The aim of the study was analysis of aetiology, staging and associated complications of CKD at the time of diagnosis. Methods. Data of 97 patients (56 boys) of average age 7.8±5.8 years, referred for the first time to the Institute for Mother and Child Healthcare „Dr Vukan Čupić”, Belgrade in the period 1998- 2009, due to CKD, stage 2-5, were analysed. In each patient illness history was obtained, and physical examination, laboratory, X-ray and other investigations were performed according to the indications. CKD was classified according to the glomerular filtration rate into four grades: 2 - mild (60-90 ml/min/1.73 m2); 3 - moderate (30-60 ml/min/1.73 m2); 4 - advanced (15-30 ml/ min/1.73 m2); and 5 - terminal (&lt;15 ml/min/1.73 m2). Results. The most frequent causes of CKD were congenital anomalies of the kidney and urinary tract (43.3%), followed by glomerular diseases (17.5%), hereditary kidney diseases (16.5%), metabolic diseases (7.2%) and other causes (15.5%). Mild CKD was found in 29.8%, moderate in 28.9%, advanced in 22.7%, and terminal in 18.6% children. Among patients with CKD stage 4 and 5, 75% of patients presented with acute renal failure, while 25% had earlier detected CKD (stage 1), but were not under regular follow-up. Associated complications included metabolic acidosis (63%), anaemia (60%), hypertension (42.3%), short stature (25.8%), renal osteodystrophy (13.4%) and cardiovascular diseases (7.2%). Conclusion. Congenital anomalies of the kidney and urinary tract are the leading cause of CKD in paediatric population. A significant proportion (41.3%) of patients had advanced and terminal CKD. In most patients CKD was diagnosed late and with associated complications