Structural and Functional Characteristics of Urinary Tract in Offspring of Balkan Endemic Nephropathy Patients

Introduction Balkan endemic nephropathy (BEN) is a familial chronic progressive tubulointerstitial disease of unknown aetiology that occurs with high prevalence in endemic rural environments of Serbia, Bosnia and Herzegovina, Croatia, Bulgaria and Romania. It has been documented only in adults. Objective The aim of this study was to examine clinical markers of BEN in children and adolescent offspring of BEN patients. Methods Prospective clinical trial involved two groups of children and adolescents: I consisted of 30 offspring of BEN patients and II of 29 offspring of non-BEN dialysis patients, both of them living in the same South Morava region of Serbia. All of them were healthy at the time of the investigation, not receiving any drugs. The study included personal and family history, physical examination, comprehensive laboratory analyses and renal ultrasound. Blood pressure (BP) was determined by using casual BP and 24 h ABPM in subjects older than 5 years. Urinary proteins were investigated by analysing microalbumin, alfa 1 microglobulin, beta 2 rnicroglobulin and SDS-PAGE electrophoresis. GFR was measured by estimated creatinine clearance and by serum Cystatin C concentrations. Results There were no statistically significant differences in age, gender, history of urinary tract infections or functional voiding disorders between these two groups. All of the studied subjects had normal BP and GFR. Renal ultrasound was abnormal only in BEN offspring (6.66%) as well as increased urine concentrations of microalbumin (3.3%), alpha 1 microglobulin (10%) and beta 2 microglobulin (13.3%) while low molecular protein ( lt 66,000 D) was prevalent in BEN compared with non-BEN offspring (21.43% vs. 3.7%). Conclusion Renal abnormalities in offspring of BEN patients may be an early marker of BEN. This has to be confirmed in long term follow-up of a greater number of BEN paediatric offspring

Pseudo-Bartter syndrome in an infant with congenital chloride Diarrhoea

Introduction Pseudo-Bartter syndrome encompasses a heterogenous group of disorders similar to Bartter syndrome. We are presenting an infant with pseudo-Bartter syndrome caused by congenital chloride diarrhoea. Case Outline A male newborn born in the 37th gestational week (GW) to young healthy and non-consanguineous parents. In the 35th GW a polyhydramnios with bowel dilatation was verified by ultrasonography. After birth he manifested several episodes of hyponatremic dehydration with hypochloraemia, hypokalaemia and metabolic alkalosis, so as Bartter syndrome was suspected treatment with indomethacin, spironolactone and additional intake of NaCl was initiated. However, this therapy gave no results, so that at age six months he was rehospitalized under the features of persistent watery diarrhoea, vomiting, dehydration and acute renal failure (serum creatinine 123 μmol/L). The laboratory results showed hyponatraemia (123 mmol/L), hypokalaemia (3.1 mmol/L), severe hypochloraemia (43 mmol/L), alkalosis (blood pH 7.64, bicarbonate 50.6 mmol/L), high plasma renin (20.6 ng/ml) and aldosterone (232.9 ng/ml), but a low urinary chloride concentration (2.1 mmol/L). Based on these findings, as well as the stool chloride concentration of 110 mmol/L, the patient was diagnosed congenital chloride diarrhoea. In further course, the patient was treated by intensive fluid, sodium and potassium supplementation which resulted in the normalization of serum electrolytes, renal function, as well as his mental and physical development during 10 months of follow-up. Conclusion Persistent watery diarrhoea with a high concentration of chloride in stool is the key finding in the differentiation of congenital chloride diarrhoea from Bartter syndrome. The treatment of congenital chloride diarrhoea consists primarily of adequate water and electrolytes replacement

Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P lt 0.001), but more HDL 3a (P lt 0.01) and 3b (P lt 0.001) subclasses. They also had increased sdLDL-C (P lt 0.01) and sdLDL-apoB (P lt 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P lt 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P lt 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy

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

Cost-effectiveness analysis of acute kidney injury biomarkers in pediatric cardiac surgery

Introduction: Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level). Materials and methods: We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER). Results: Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was$5959.35/QALY. Conclusions: Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery

Clinical Application Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as Indicators of Inflammation Persistence and Acute Kidney Injury in Children with Urinary Tract Infection

Background. The aim of this study was to examine the novel renal biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assist pediatricians in the assessment of longer duration of inflammation and acute kidney injury (AKI) development during urinary tract infection (UTI). Methods. The patients enrolled in the study comprised 50 children (mean age was 6 months) with UTI. NGAL in serum and urine (sNGAL and uNGAL, resp.) and KIM-1 in urine were measured by enzyme-linked immunosorbent assays. Results. uNGAL levels in subjects with longer duration of inflammation were higher (115.37 ng/mL) than uNGAL levels in subjects with shorter duration of inflammation (67.87 ng/mL, P = 0.022). Difference in sNGAL and KIM-1 levels was not significant (P = 0.155 and P = 0.198, resp.). Significant difference was seen in KIM-1 excretion among groups with and without AKI (P = 0.038). KIM-1 was not able to discriminate between subjects with and without AKI (area under the curves (AUC) = 0.620, P = 0.175). Conclusions. uNGAL cannot be used for screening of the duration of inflammation during UTI. Accuracy of KIM-1 in screening of AKI development in children with UTI is low. We suggest larger studies to check the negative predictive value of KIM-1 for the development of AKI

Oxidative status parameters in children with urinary tract infection

Introduction: Urinary tract infection (UTI) is one of the most common bacterial infectious diseases in children. The aim of this study was to determine the total prooxidant and antioxidant capacity of children with UTI, as well as changes of oxidative status parameters according to acute inflammation persistence and acute kidney injury (AKI) development. Materials and methods: The patients enrolled in the study comprised 50 Caucasian children (median age was 6 months) with UTI. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), inflammation marker C-reactive protein (CRP) and renal function parameters urea and creatinine were analyzed in patient's serums. Results: According to duration of inflammation during UTI, TAS values were significantly higher (0.99 vs. 0.58 mmol/L, P = 0.017) and OSI values were significantly lower (0.032 vs. 0.041 AU, P = 0.037) in the subjects with longer duration of inflammation than in the subjects with shorter duration of inflammation. We did not find significant difference in basal values of oxidative status parameters according to AKI development. Conclusions: OSI values could detect the simultaneous change of TAS and TOS due to change in the oxidative-antioxidant balance during the recovery of children with UTI. TAS and OSI as markers of oxidative stress during UTI are sensitive to accompanying inflammatory condition. Further investigations are needed to evaluate whether TAS, TOS and OSI could be used to monitor disease severity in children with UTI

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

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