Publications by authors named "Amira Peco-Antic"

88 Publications

The influence of oxidative stress on cardiac remodeling in obese adolescents.

Scand J Clin Lab Invest 2018 Nov - Dec;78(7-8):595-600

a Nephrology Department , University Children's Hospital , Belgrade , Serbia.

Oxidative stress seems to be an important link between obesity and cardiovascular disease. The aim of our study was to assess oxidative stress in obese patients stratified according to ambulatory blood pressure status and to determine independent predictors of abnormal left ventricular geometry.A cross-sectional study was conducted. A total of 113 obese participants referred for 24-h ambulatory blood pressure monitoring (ABPM) aged 9-19 years, and 29 healthy controls were enrolled. In addition to anthropometric and biochemical measurements, such as fasting serum levels of glucose, insulin, lipid profile, and oxidative biomarkers, ABPM and echocardiography were performed.According to ABPM results, obese subjects were split in two groups: 57 hypertensive and 56 normotensive. Both hypertensive and normotensive obese participants had higher levels of oxidative stress parameters (pro-oxidative/antioxidative balance and total oxidant status) compared with control group. Levels of superoxide anion (O) and sulfhydryl groups were higher in obese hypertensive participants as compared to obese normotensive and control groups. Abnormal left ventricular geometry among obese participants was independently associated with O (p = .006) and body mass index z score (p = .020), with no significant impact of gender, while age and systolic blood pressure exhibited interaction term for the outcome.The independent effect of oxidative mechanisms on left ventricular geometry appears to start in childhood. Oxidative stress occurs in obese adolescents prior to the development of sustained hypertension.
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http://dx.doi.org/10.1080/00365513.2018.1528504DOI Listing
April 2019

Prevalence of Hypertension in Children with Early-Stage ADPKD.

Clin J Am Soc Nephrol 2018 06 19;13(6):874-883. Epub 2018 Apr 19.

Division of Nephrology, Department of Pediatric Subspecialties, and

Background And Objectives: Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited.

Design, Setting, Participants, & Measurements: Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected.

Results: Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; =0.10).

Conclusions: These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.
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http://dx.doi.org/10.2215/CJN.11401017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989684PMC
June 2018

Serum glutathione S-transferase Pi as predictor of the outcome and acute kidney injury in premature newborns.

Pediatr Nephrol 2018 07 23;33(7):1251-1256. Epub 2018 Feb 23.

School of Medicine, Institute for Child and Youth Health Care of Vojvodina, NICU/PICU, University of Novi Sad, Hajduk Veljkova 10, Novi Sad, 21000, Serbia.

Background: The incidence of acute kidney injury (AKI) among the neonates treated at the Neonatal Intensive Care Unit is high with high mortality rates. Glutathione S-transferase (GST) class Pi plays an important role in the protection of cells from cytotoxic and oncogenic agents. The aim of the study was to examine whether the levels of serum glutathione S-transferase Pi (GST Pi) determined after birth have any predictive value for the outcome and development of AKI in premature neonates.

Methods: The prospective study included 36 premature neonates. The data about morbidity was gathered for all the neonates included in the study. The blood samples were taken in the first 6 h of life and GST Pi levels were measured.

Results: The mean values and standard deviations of GST Pi among the neonates who died and who survived were 1.904 ± 0.4535 vs 1.434 ± 0.444 ng/ml (p = 0.0128). Logistic regression revealed a statistically significant, positive correlation between GST Pi levels and death (p = 0.0180, OR7.5954; CI 1.4148-40.7748).The mean value of GST Pi levels in the neonates with AKI was higher than in neonates without AKI (p = 0.011).

Conclusions: The conclusion of our study is that high levels of serum GST Pi in the first 6 h after birth are associated with an increased mortality and development of AKI in prematurely born neonates.
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http://dx.doi.org/10.1007/s00467-018-3910-xDOI Listing
July 2018

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

Turk J Med Sci 2017 Dec 19;47(6):1804-1812. Epub 2017 Dec 19.

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 < 9 had significantly higher percentages of small, dense LDL particles (P < 0.05), due to reduced LDL I (P < 0.01) and increased LDL III subclasses (P < 0.05). Birth weight was positively associated with the proportions of LDL I particles (P < 0.001), whereas birth height positively correlated with the amount of HDL 2b subclasses (P < 0.05). The group of never or less than 3 months breastfed children had significantly smaller LDL size (P < 0.01) and lower proportion of HDL 2a particles (P < 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.
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http://dx.doi.org/10.3906/sag-1702-164DOI Listing
December 2017

Alterations of HDL Particles in Children with End-stage Renal Disease.

J Med Biochem 2017 Oct 28;36(4):358-365. Epub 2017 Oct 28.

Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

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.

Conclusion: Children with CKD have impaired HDL distribution that is improved after kidney transplantation. Since that measurement of HDL distribution and functionality are not routinely available, MPO/PON1 ratio may be useful marker that could provide necessary information.
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http://dx.doi.org/10.1515/jomb-2017-0019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294087PMC
October 2017

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

Kidney Int 2017 12 18;92(6):1507-1514. Epub 2017 Jul 18.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany. Electronic address:

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.
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http://dx.doi.org/10.1016/j.kint.2017.05.006DOI Listing
December 2017

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

J Med Biochem 2017 Jan 25;36(1):23-31. Epub 2017 Jan 25.

Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

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<0.001), as well as the atherogenic index of plasma (p<0.001). Myeloperoxidase concentration and advanced oxidation protein product (AOPP) concentration were independently associated with increased AIP in the patient group (p<0.05).

Conclusions: Changes in AIP in children with ERSD are associated with the oxidative stress status and myeloper-oxidase concentration.
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http://dx.doi.org/10.1515/jomb-2016-0027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471656PMC
January 2017

Association of paraoxonase 1 and oxidative stress with acute kidney injury in premature asphyxiated neonates.

Chem Biol Interact 2017 Jun 20;272:47-52. Epub 2017 Apr 20.

School of Medicine, University of Belgrade, Department of Nephrology, University Children's Hospital, Tiršova 10, 11000 Belgrade, Serbia.

Objectives: Acute kidney injury (AKI) is defined as a decrease in glomerular filtration rate with an increase in serum creatinine (sCr). Perinatal asphyxia (PNA) may be etiological factor for AKI with oxidative stress also implicated. Paraoxonase 1 (PON1) activity has been reported to be decreased in renal disease. The aim of our study was to evaluate paraoxonase 1 (PON1) activity and oxidative stress during the first hours and first days of life and to determine if these parameters could discriminate neonates having AKI from those who do not.

Methods: Serum samples at different time points after birth were obtained from 64 preterm newborns with PNA (45 defined as having AKI, 19 as non-AKI). Clinical markers, sCr, total oxidant status (TOS), total antioxidant status (TAS) and PON1 activity were measured.

Results: The AKI group had more newborns with hypoxic ischemic encephalopathy, significantly higher serum creatinine (sCr) at 3 and 7d, total antioxidant status (TAS) at 7d; decreased PON1 at 4h, 6h and 7d than the non-AKI group. Within the AKI group, significant positive correlations were found between PON1 activity at 2h and TAS at 2h, PON1 activity at 4h and base deficit (BD); whereas negative correlations between PON1 activity at 2h and ΔsCr (at 24h and at 3d), PON1 activity at 7d and ΔsCr (at 24h and 3d). Oxidative stress status parameters indicated excellent discriminative potential at 4h, 6h and 7d.

Conclusions: AKI neonates were characterised by a marked decrease in PON1 activity. PON1 activity may be an important factor for discrimination of newborns having AKI from those that do not.
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http://dx.doi.org/10.1016/j.cbi.2017.04.014DOI Listing
June 2017

Shiga toxin-producing Escherichia coli hemolytic uremic syndrome.

Srp Arh Celok Lek 2016 Nov-Dec;144(11-12):664-9

The hemolytic–uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). The major cause of HUS in childhood (>90%) is infection with verocytotoxin (Shiga-like toxin – “Stx”)-producing bacteria, usually enterohemorrhagic Escherichia coli (VTEC/STEC). The infection may be transmitted by the consumption of undercooked meat, pasteurized dairy products, contaminated vegetables, fruits and water, or by contact with STEC diarrhea. After an incubation period of three to eight days, patients commonly develop bloody diarrhea followed in 5–22% by HUS that may be complicated by central nervous system, pancreatic, skeletal, and myocardial involvement. HUS is one of the main causes of AKI in children in Europe. The management of HUS includes the usual treatment of children with AKI. Transfusion with packed red blood cells is needed in case of a severe anemia, while platelet transfusions are limited to the need for a surgical procedure or in active bleeding. Currently, there is no consensus on the use of antibiotic therapy. Treatment with plasma and/or plasma exchange has not been proven beneficial in STEC-HUS. Eculizumab has been used for the treatment of STEC-HUS, but the value of this treatment remains to be determined. The mortality of HUS is reported to be 3–5%. About 12% of patients will progress to end-stage renal failure within four years and about 25% will have long-term complications, including hypertension, proteinuria, renal insufficiency, and insulin-dependent diabetes mellitus. Transplantation can be performed without increased risk for the recurrence of the disease.
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http://dx.doi.org/10.2298/sarh1612664pDOI Listing
May 2018

Granulomatous interstitial nephritis associated with influenza A: H1N1 infection--A case report.

Srp Arh Celok Lek 2016 Mar-Apr;144(3-4):215-8

Introduction: The causes of acute tubulointerstitial nephritis can be grouped into four broad categories: medications, infections, immunologic diseases, or idiopathic processes. Here we report a 17-year-old female who developed acute kidney injury (AKI) due to granulomatous interstitial nephritis (GIN) associated with influenza A: H1N1 infection.

Case Outline: The illness presented after two weeks of respiratory tract infection, skin rash and hypermenorrhea. On admission the patient was febrile, with bilateral pedal edema, macular skin rash, and auscultatory finding that suggested pneumonia. Laboratory investigations showed normocytic anemia, azotemia, hematuria and proteinuria. Renal ultrasound was normal. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, lupus anticoagulant, antiphospholipid antibodies were negative with normal complement. Urine cultures including analysis for Mycobacterium tuberculosis were negative. The diagnosis of influenza A: H1N1 infection was made by positive serology. A kidney biopsy showed interstitial nephritis with peritubular granulomas. Glomeruli were normal. Staining for immunoglobulins A, M, G, and F was negative. The girl was treated with oseltamivir phosphate (Tamiflu; Genentech, Inc., South San Francisco, CA, USA) for five days, as well as with tapered prednisone after a starting dose of 2 mg/kg. The treatment resulted in a complete remission during two years of follow-up.

Conclusion: We present a severe but reversible case of GIN and AKI associated with influenza A: H1N1 infection. Although a causal effect cannot be confirmed, this case suggests that influenza A: H1N1 should be considered in the differential diagnosis of GIN manifested with AKI in children.
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August 2016

Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents.

Scand J Clin Lab Invest 2016 Oct 5;76(6):472-8. Epub 2016 Jul 5.

a Department of Medical Biochemistry, Faculty of Pharmacy , University of Belgrade , Belgrade , Serbia ;

Background: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children.

Methods: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters.

Results: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = -0.423; p = 0.025) in the group with hypertension.

Conclusions: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.
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http://dx.doi.org/10.1080/00365513.2016.1201849DOI Listing
October 2016

Detection of acute kidney injury in premature asphyxiated neonates by serum neutrophil gelatinase-associated lipocalin (sNGAL)--sensitivity and specificity of a potential new biomarker.

Biochem Med (Zagreb) 2015 15;25(3):450-9. Epub 2015 Oct 15.

School of Medicine, University of Belgrade, University Children's Hospital, Department of Nephrology, Belgrade, Serbia.

Introduction: Acute kidney injury (AKI) is common in neonatal intensive care units (NICU). In recent years, every effort is made for early detection of AKI. Our hypothesis was that serum neutrophil gelatinase-associated lipocalin (sNGAL) may be a reliable screening test for early diagnosis of AKI in premature neonates after perinatal asphyxia. Therefore, our aim was to assess the diagnostic accuracy of sNGAL for AKI in premature asphyxiated neonates.

Materials And Methods: AKI was defined in the third day of life (DOL 3) as a serum creatinine (sCr) increase ≥26.5 μmol/L from baseline (the lowest previous sCr). According to the increase of sCr, AKI patients were divided in AKIN1 (sCr increase up to 1.9 baseline) and AKIN2 (sCr increase from 2.0 to 2.9 baseline). sNGAL levels were measured on DOL 1, 3 and 7.

Results: AKI was diagnosed in 73 (0.676) of 108 enrolled premature asphyxiated neonates. Sixty one patients (0.836) were classified in AKIN1 and 12 patients (0.164) in AKIN2. sNGAL reached the maximal concentrations on DOL 1 within 4 hours after admission to NICU, being higher in AKI compared with no-AKI group (160.8±113.1 vs. 87.1±81.6; P<0.001) as well as in AKIN2 compared with AKIN1 group (222.8±112.9 vs. 147.8±109.9; P<0.001). The best areas under the receiver operating characteristic curves (AUC) for prediction of AKI were 0.72 [95% (0.62-0.80) P<0.001] on DOL1 at 2h and 0.72 [95% (0.63-0.80) P<0.001] at 4th hour after admission respectively. The corresponding sNGAL cutoff concentrations were 84.87 ng/mL (sensitivity 69.0% and specificity 71.9%) and 89.43 ng/mL (sensitivity 65.7% and specificity 74.3%).

Conclusions: In premature asphyxiated neonates sNGAL measured within the first 4 hours of DOL 1 is predictive of the occurrence and severity of AKI. Therefore, plasma levels of NGAL may be used for early diagnosis of AKI in these patients.
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http://dx.doi.org/10.11613/BM.2015.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622185PMC
December 2015

Associated extrarenal vascular diseases may complicate the treatment and outcome of renovascular hypertension.

Acta Paediatr 2016 Jan 4;105(1):e35-41. Epub 2015 Nov 4.

Nephrology Department, University Children's Hospital, Belgrade, Serbia.

Aim: This studied reviewed renovascular hypertension (RVH) due to renal artery stenosis (RAS) in two Serbian paediatric centres from 2001 to 2013.

Methods: The patients' demographic data, underlying syndromes, blood pressure (BP), antihypertensive treatments and outcomes were reviewed.

Results: The incidence of RVH was 1.9 per million children per year during the study period, and there were 25 patients with RAS, aged 10.4 ± 5.2 years. At presentation, their mean blood pressure (BP) standard deviation scores were 6.9 ± 3.4 systolic and 5.2 ± 2.6 diastolic. BP loads on 24-hour ambulatory BP were 88 ± 14% systolic and 80 ± 29% diastolic. We found that 72% had fibromuscular dysplasia and 28% had underlying syndromes. RAS was unilateral in 64% and bilateral in 28%, and 8% had RAS of a single kidney. Antihypertensive treatment included antihypertensive drugs (100%), percutaneous transluminal angioplasty (92%), renal auto-transplantation (16%), surgical revascularisation (12%) and nephrectomy (12%). After 4.4 ± 3.6 years of follow-up, high BP was cured in 40% of the patients and 39.4% of the kidneys and improved in 48% (75.7%), with BP decreases of 20.3 ± 3.7% systolic and 16.3 ± 6.2% diastolic.

Conclusion: Fibromuscular dysplasia was the most common cause of RVH in this study, and hypertension was cured or improved in 88% of the patients.
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http://dx.doi.org/10.1111/apa.13229DOI Listing
January 2016

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

Biochem Med (Zagreb) 2015 5;25(2):262-71. Epub 2015 Jun 5.

Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

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.
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http://dx.doi.org/10.11613/BM.2015.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470097PMC
August 2015

Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates.

Pediatr Res 2015 Oct 24;78(4):430-5. Epub 2015 Jun 24.

Department of Nephrology, University Children Hospital, Faculty of Medicine University of Belgrade, Belgrade, Serbia.

Background: The new urinary and serum biomarkers are discovered and are being investigated. With them we can diagnose acute kidney injury (AKI) faster and more precisely and they also have a significant role in the outcome prediction.

Methods: The study included 22 extremely low-birth-weight neonates who were hospitalized in the neonatal intensive care units. They were divided into two groups based on serum creatinine (SCr) level-with and without AKI. Detection and quantification of urinary kidney injury molecule-1 (uKIM-1) was done on the third day of life, using commercially available KIM-1 rapid test. Subsequently, measurements were repeated only in subjects who were diagnosed with AKI, at different values of SCr.

Results: Logistic regression analysis showed that AKI is an independent risk factor for mortality. In a group of neonates with AKI, 50% of neonates administered the KIM-1 rapid test showed positive findings. KIM-1 rapid test was positive in patients with a wide range of SCr levels (range of 78.73-385 µmol/l), but all subjects had oliguria and died in the next 24 h.

Conclusion: KIM-1 is a significant predictor of death. On the other hand, our study failed to prove that KIM-1 rapid test has any significance for early prediction of AKI.
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http://dx.doi.org/10.1038/pr.2015.125DOI Listing
October 2015

[Develooment of the lower urinary tract and its functional disorders].

Srp Arh Celok Lek 2015 Mar-Apr;143(3-4):219-25

A normal development of lower urinary tract function control evolves from involuntary bladder empting (incontinence) during infancy to daytime urinary continence, and finally a successful day and night continence that is generally achieved by the 5th to 7th year of age.This gradual process primarily depends on the progressive maturation of the neural control of the lower urinary tract, but it is also influenced by behavioral training that evolves through social support. Functional voiding disorders (bladder dysfunction) are common problems during childhood. They are present in 5-15 % of general pediatric population, and in one-fifth of school-age children or in over one-third of patients of the pediatric urologist or nephrologist. More than half of children with bladder dysfunction have vesicoureteral reflux, and more than two-thirds have recurrent urinary tract infections. There is also a frequent association of bladder dysfunction with constipation and encopresis (dysfunctional elimination syndrome). Bladder dysfunction may cause a permanent damage to the upper urinary tract and kidneys. In addition, urinary incontinence, as the most common manifestation of bladder dysfunction can be the cause of major stress in school- age children and have a negative effect on the child's feeling of self-esteem. Thus, a timely detection and treatment of this group of disorders in children is highly significant.
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http://dx.doi.org/10.2298/sarh1504219pDOI Listing
October 2015

Genetic abnormalities and prognosis in patients with congenital and infantile nephrotic syndrome.

Pediatr Nephrol 2015 Aug 27;30(8):1279-87. Epub 2015 Feb 27.

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

Background: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are caused primarily by mutations in genes that encode structural and regulatory proteins of the glomerular filtration barrier. The aim of this study was to determine genotype-phenotype correlations and prognosis in patients with CNS and INS.

Methods: NPHS1, NPHS2, LAMB2 and the eighth and ninth exons of WT1 were sequenced in 80 and 22 patients with CNS and INS, respectively. Genotype-phenotype correlations and survival were evaluated.

Results: Causative mutations were identified in 64.7 % of patients, of which NPHS1 mutations were the most common (37.4 %). The mutation detection rate was twofold higher in CNS patients than in INS patients (72.5 vs. 36.2 %). The most commonly mutated gene in CNS patients was NPHS1 (46.3 %) versus NPHS2 (13.6 %) and WT1 (13.6 %) in INS patients. NPHS2 mutations, female patients with NPHS1 mutations, and NPHS1 mutations affecting the transmembrane or intracellular domains of nephrin were associated with longer survival.

Conclusions: Based on our present findings, the likelihood of identification of a genetic cause decreases with increasing age at diagnosis. The underlying genetic abnormality should be identified as early as possible, as this knowledge will facilitate clinicians in their prognostic prediction and enable patients to receive appropriate genetic counseling.
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http://dx.doi.org/10.1007/s00467-015-3058-xDOI Listing
August 2015

Pathogens causing urinary tract infections in infants: a European overview by the ESCAPE study group.

Eur J Pediatr 2015 Jun 28;174(6):783-90. Epub 2014 Nov 28.

Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant'Orsola-Malpighi Bologna, Via Massarenti 11, 40138, Bologna, Italy,

Unlabelled: Knowledge of the distribution spectrum of causative organisms and their resistance patterns has become a core requirement for the rational and effective management of urinary tract infections. In the context of a prospective trial on the use of antibiotic prophylaxis in infants with underling kidney malformations, we conducted an online survey among paediatric nephrologists on positive urine cultures (July 2010-June 2012) from both hospitalized and non-hospitalized infants under 24 months of age. We collected 4745 urine cultures (UCs) at 18 units in 10 European countries. Escherichia coli was the most frequent bacterium isolated from UCs; however, in 10/16 hospitals and in 6/15 community settings, E. coli was isolated in less than 50% of the total positive UCs. Other bacterial strains were Klebsiella, Enterococcus, Proteus and Pseudomonas not only from hospital settings. E. coli showed a high resistance to amoxicillin and trimethoprim and variable to cephalosporin. Nitrofurantoin had a good rate of efficacy, with 11/16 hospitals and 11/14 community settings reporting a resistance lower than 5%.

Conclusion: E. coli is the most common organism causing UTIs in infants; however, other bacterial strains are frequently isolated. As a result, antibiotic prophylaxis should be more elastic and adaptable over time in order to guarantee maximum efficacy.
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http://dx.doi.org/10.1007/s00431-014-2459-3DOI Listing
June 2015

Left ventricular mass and diastolic function in obese children and adolescents.

Pediatr Nephrol 2015 Apr 30;30(4):645-52. Epub 2014 Oct 30.

Nephrology Department, University Children's Hospital, Tiršova 10, 11 000, Belgrade, Serbia,

Background: Our aims were to assess left ventricular structure and diastolic function in obese subjects stratified according to ambulatory blood pressure status, and to investigate independent predictors of the left ventricular mass (LVM) index.

Methods: Obese subjects aged 9-19 years referred for ambulatory blood pressure monitoring (ABPM) were evaluated in the cross-sectional study. In addition to biochemical and anthropometric measurements, subjects underwent ABPM, Doppler echocardiography, and treadmill exercise test.

Results: According to ABPM results, 103 subjects with obesity (mean age 14.1 ± 2 years) were split in two groups: 49 hypertensive, and 54 without hypertension. Left ventricular hypertrophy was found in 16.3 % of hypertensive, and 5.6 % of normotensive. Variables included in stepwise regression analysis as potential determinants of LVM index were age, body mass index z score, waist circumference, peak systolic blood pressure on exercise test, 24-h heart rate, and night heart rate. Peak systolic blood pressure (adjusted R(2) = 0.051, β = 0.245, p = 0.013) remained as the independent predictor of LVM index. Diastolic function evaluated by mitral E/A ratio was decreased in both obese groups.

Conclusions: Early markers of cardiac disease including hypertrophy and diastolic dysfunction of the left ventricle are present in youths with obesity prior to the development of sustained hypertension.
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http://dx.doi.org/10.1007/s00467-014-2992-3DOI Listing
April 2015

Glomerular nestin expression: possible predictor of outcome of focal segmental glomerulosclerosis in children.

Pediatr Nephrol 2015 Jan 18;30(1):79-90. Epub 2014 Aug 18.

Medical Faculty, University of Belgrade, Belgrade, Serbia.

Background: A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated.

Methods: Among 649 renal biopsy samples, obtained from two children's hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 ± 5.2 years. Using Kaplan-Meier and Cox's regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy.

Results: The present study revealed the following significant predictors of kidney dysfunction: patients' ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression.

Conclusions: The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy.
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http://dx.doi.org/10.1007/s00467-014-2893-5DOI Listing
January 2015

Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry.

Pediatr Nephrol 2014 Dec 21;29(12):2403-10. Epub 2014 Jul 21.

Department of Medical Informatics, Academic Medical Center, Amsterdam, The Netherlands.

Background: The ESPN/ERA-EDTA Registry collects data on European children with end-stage renal disease receiving renal replacement therapy (RRT) who are listed on national and regional renal registries in Europe. In this paper we report on the analysis of demographic data collected from 2009 to 2011.

Methods: Data on primary renal disease, incidence, prevalence, 4-year survival, transplantation rate and causes of death in paediatric patients receiving RRT were extracted from the ESPN/ERA-EDTA Registry for 37 European countries.

Results: The incidence of RRT in paediatric patients in Europe during the study period was 5.5 cases per million age-related population (pmarp) in patients aged 0-14 years and varied markedly between countries (interquartile range 3.4-7.0 years). The prevalence of RRT was 27.9 pmarp and increased with age, with 67 % of prevalent patients living with a functioning graft. The probability of receiving a transplant within 4 years was 76.9 % and was lowest in patients aged 0-4 years (68.9 %). Mortality in paediatric patients treated with RRT was 55-fold higher than that of the general EU paediatric population. Overall survival at 4 years was 93.7 %, with the poorest survival in patients aged 0-4 years and in patients starting on dialysis. Infections (19.9 %) were the primary cause of death in European paediatric RRT patients.

Conclusion: Considerable variation exists in the current demographics of children treated with RRT across Europe.
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http://dx.doi.org/10.1007/s00467-014-2884-6DOI Listing
December 2014

[Acute kidney injury in children].

Srp Arh Celok Lek 2014 May-Jun;142(5-6):371-7

Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.
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http://dx.doi.org/10.2298/sarh1406371pDOI Listing
October 2015

Oxidative status parameters in children with urinary tract infection.

Biochem Med (Zagreb) 2014 15;24(2):266-72. Epub 2014 Jun 15.

Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

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.

Conclusion: 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.
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http://dx.doi.org/10.11613/BM.2014.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083578PMC
July 2014

Growth in children with chronic kidney disease: 13 years follow up study.

J Nephrol 2014 Oct 23;27(5):537-44. Epub 2014 Apr 23.

Medical Faculty, University of Belgrade, Belgrade, Serbia,

Background: Growth retardation is one of the most visible comorbid conditions of chronic kidney disease (CKD) in children. To our knowledge, published data on longitudinal follow-up of growth in pediatric patients with CKD is lacking from the region of South-East Europe. Herein we report the results from the Serbian Pediatric Registry of Chronic Kidney Disease.

Methods: The data reported in the present prospective analysis were collected between 2000 and 2012. A total of 324 children with CKD were enrolled in the registry.

Results: Prevalence of growth failure at registry entry was 29.3 %. Mean height standard deviation scores (HtSDS) in children with stunting and those with normal stature were -3.00 [95 % confidence interval (CI) -3.21 to -2.79] and -0.08 (95 % CI -0.22 to 0.05) (p < 0.001), respectively. Children with hereditary nephropathy had worse growth at registration (-1.51; 95 % CI -1.97 to -1.04, p = 0.008). Those with CKD stages 4 and 5 before registration had more chance to have short stature at registration than those with CKD stages 2 and 3 [odds ratio (OR) = 0.458, CI 0.268-0.782, p = 0.004]. Dialysis was an independent negative predictor for maintaining optimal stature during the follow-up period (OR = 0.324, CI = 0.199-0.529, p < 0.001), while transplantation was an independent positive predictor for improvement of small stature during follow-up (OR = 3.706, CI = 1.785-7.696, p < 0.001).

Conclusion: Growth failure remains a significant problem in children with CKD, being worst in patients with hereditary renal disease. Growth is not improved by standard dialysis, but transplantation has a positive impact on growth in children.
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http://dx.doi.org/10.1007/s40620-014-0094-8DOI Listing
October 2014

Early biomarkers of renal injury and protective effect of erythropoietin on kidneys of asphyxiated newborn rats.

Pediatr Res 2014 Jul 8;76(1):11-6. Epub 2014 Apr 8.

1] Department of Nephrology, University Children's Hospital, Belgrade, Serbia [2] Medical School, University of Belgrade, Belgrade, Serbia.

Background: The aims of this study were to determine which of the two biomarkers of renal injury, kidney injury molecule-1 or cystatin C, is more sensitive and to evaluate whether erythropoietin protects kidneys injured by perinatal asphyxia.

Methods: Animals were split into three groups designated as follows: AE, pups that survived perinatal asphyxia and subsequently received 2.5 μg (0.1 ml) of darbepoetin-α (i.p.); A, the pups that survived perinatal asphyxia and received 0.1 ml of 0.9% NaCl; and C, control group. The pups were killed at different ages of life (6 h, 24 h, 48 h, 7 d, and 14 d of age; 10 rats in each subgroup). Immunohistopathological evaluation of kidneys was performed.

Results: At 48 h and on days 7 and 14, absolute injury scores were significantly lower in group AE as measured by both biomarkers. Cystatin C expression was the most intensive 6 h after the hypoxic event (average value of absolute injury score was 2.82) and declined over time. Expression of kidney injury molecule-1 was less intensive, with the average value of absolute injury score being 2.02 at 6 h and 2.105 at 24 h; the peak value (2.155) was recorded 48 h after the hypoxic event.

Conclusion: Erythropoietin has a protective effect on hypoxic kidneys. Cystatin C is more sensitive as an early biomarker of acute kidney injury in comparison with kidney injury molecule-1.
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http://dx.doi.org/10.1038/pr.2014.50DOI Listing
July 2014

Renal hypertension and cardiovascular disorder in children with chronic kidney disease.

Srp Arh Celok Lek 2014 Jan-Feb;142(1-2):113-7

Renal hypertension is one of the earliest and the most prevalent complications of pediatric chronic kidney disease (CKD). Among renal patients, hypertension is frequently underdiagnosed and undertreated. For casual blood pressure measurement, the best method is auscultatory, while for ambulatory blood pressure measurement, oscillometric method is the most commonly used. Both casual and ambulatory blood pressure measurement provide more powerful means of diagnosing hypertension. Masked hypertension is a condition in which casual blood pressure is normal but ambulatory blood pressure is elevated. The risk of cardiovascular morbidity and mortality is higher with masked hypertension as compared to the controls. Children and adolescents with CKD are at high risk of cardiovascular disease that has been established as the leading cause of death in patients with end stage renal disease. Left ventricular hypertrophy remains the most thoroughly documented form of end-organ damage caused by hypertension in children and adolescents with CKD. Based on clear evidence on the correlation between blood pressure and cardiovascular morbidity, mortality, and renal function, renal hypertension must be aggressively treated. Target blood pressure for patients with renal hypertension should be at low normal values: < 75 percentile for patients without proteinuria and <50 percentile for patients with proteinuria. Renin-angiotensin system antagonists are considered the first choice pharmacological option in hypertensive CKD 2-4 patients while the management of volume overload is the most important in dialysis patients. Successful transplantation can eliminate or significantly improve uremia-related cardiovascular risk factors and increase predicted life expectancy.
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http://dx.doi.org/10.2298/sarh1402113pDOI Listing
October 2015

Post-transplant lymphoproliferative disorder--case reports of three children with kidney transplant.

Srp Arh Celok Lek 2014 Jan-Feb;142(1-2):83-8

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of diseases, characterized by abnormal lymphoid proliferation following transplantation. It is a disease of the immunosuppressed state, and its occurrence is mostly associated with the use of T-cell depleting agents, and also intensification of immunosuppressive regimens. In the majority of cases, PTLD is a consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The 2008 World Health Organization classification for lymphoid malignancies divides PTLD into four major categories: early lesions, polymorphic PTLD, monomorphic PTLD and Hodgkin PTLD. The treatment and prognosis depend on histology. The cornerstone of PTLD therapy includes reduction/withdrawal of immunosuppression, monoclonal anti CD-20 antibody (rituximab) and chemotherapy.

Outline Of Cases: We reported here our experiences with three patients, two girls aged 7.5 and 15 and a 16-year old boy. They had different organ involvement: brain, combined spleen-liver and intestines, respectively. Even though EBV was a trigger of lymphoid proliferation as it was confirmed by histopathology or in cerebrospinal fluid, qualitative EBV-PCR was positive only in one patient at disease presentation. Reduction of immunosuppression therapy was applied in treatment of all three patients, while two of them received rituximab and ganciclovir. They had an excellent outcome besides many difficulties in diagnosis and management of disease.

Conclusion: Qualitative EBV-PCR is not useful marker in pediatric transplant recipients. Our suggestion is that patients with the risk factors like T-cell depleting agents, immunosuppressant protocol or increasing immunosuppressive therapy and EBV miss-match with donor must be more accurately monitored with quantitative EBV PCR.
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http://dx.doi.org/10.2298/sarh1402083sDOI Listing
October 2015

Genotype-phenotype associations in WT1 glomerulopathy.

Kidney Int 2014 May 8;85(5):1169-78. Epub 2014 Jan 8.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.

WT1 mutations cause a wide spectrum of renal and extrarenal manifestations. Here we evaluated disease prevalence, phenotype spectrum, and genotype-phenotype correlations of 61 patients with WT1-related steroid-resistant nephrotic syndrome relative to 700 WT1-negative patients, all with steroid-resistant nephrotic syndrome. WT1 patients more frequently presented with chronic kidney disease and hypertension at diagnosis and exhibited more rapid disease progression. Focal segmental glomerulosclerosis was equally prevalent in both cohorts, but diffuse mesangial sclerosis was largely specific for WT1 disease and was present in 34% of cases. Sex reversal and/or urogenital abnormalities (52%), Wilms tumor (38%), and gonadoblastoma (5%) were almost exclusive to WT1 disease. Missense substitutions affecting DNA-binding residues were associated with diffuse mesangial sclerosis (74%), early steroid-resistant nephrotic syndrome onset, and rapid progression to ESRD. Truncating mutations conferred the highest Wilms tumor risk (78%) but typically late-onset steroid-resistant nephrotic syndrome. Intronic (KTS) mutations were most likely to present as isolated steroid-resistant nephrotic syndrome (37%) with a median onset at an age of 4.5 years, focal segmental glomerulosclerosis on biopsy, and slow progression (median ESRD age 13.6 years). Thus, there is a wide range of expressivity, solid genotype-phenotype associations, and a high risk and significance of extrarenal complications in WT1-associated nephropathy. We suggest that all children with steroid-resistant nephrotic syndrome undergo WT1 gene screening.
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http://dx.doi.org/10.1038/ki.2013.519DOI Listing
May 2014

Proteinuria in Frasier syndrome.

Srp Arh Celok Lek 2013 Sep-Oct;141(9-10):685-8

School of Medicine, University of Belgrade, Belgrade, Serbia.

Introduction: Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms'tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure.

Case Outline: We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria.

Conclusion: RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.
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http://dx.doi.org/10.2298/sarh1310685pDOI Listing
October 2015

Underweight, overweight and obesity in paediatric dialysis and renal transplant patients.

Nephrol Dial Transplant 2013 Nov 23;28 Suppl 4:iv195-iv204. Epub 2013 Aug 23.

ESPN/ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: The prevalence of childhood overweight is rising worldwide, but in children on renal replacement therapy (RRT) a poor nutritional status is still the primary concern. We aimed to study the prevalence of, and factors associated with, underweight and overweight/obesity in the European paediatric RRT population. Moreover, we assessed the evolution of body mass index (BMI) after the start of RRT.

Methods: We included 4474 patients younger than 16 years from 25 countries of whom BMI data, obtained between 1995 and 2010, were available within the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Prevalence estimates for under- and overweight/obesity were calculated using age and sex-specific criteria of the World Health Organization (WHO, 0-1 year olds) and the International Obesity Task Force cut-offs (2-15 year olds).

Results: The prevalence of underweight was 3.5%, whereas 20.8% of the patients were overweight and 12.5% obese. Factors associated with being underweight were receiving dialysis treatment and infant age. Among transplanted recipients, a very short stature (OR: 1.64, 95% CI: 1.40-1.92) and glucocorticoid treatment (OR: 1.23, 95% CI: 1.03-1.47) were associated with a higher risk of being overweight/obese. BMI increased post-transplant, and a lower BMI and a higher age at the start of RRT were associated with greater BMI changes during RRT treatment.

Conclusions: Overweight and obesity, rather than underweight, are highly prevalent in European children on RRT. Short stature among graft recipients had a strong association with overweight, while underweight appears to be only a problem in infants. Our findings suggest that nutritional management in children receiving RRT should focus as much on the prevention and treatment of overweight as on preventing malnutrition.
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http://dx.doi.org/10.1093/ndt/gft259DOI Listing
November 2013