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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, program med 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 disease, 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 (rs=0.42, p=0.027 and rs=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 antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome.
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Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and ß-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). ß-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/ß-sitosterol (P < 0.001) and 7-DHC/ß-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission.
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Desmosterol , Síndrome Nefrótico , Niño , Preescolar , HDL-Colesterol , Humanos , Lipoproteínas , Espectrometría de Masas en TándemRESUMEN
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; P=0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P=0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P=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; P=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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Hipertensión/epidemiología , Riñón Poliquístico Autosómico Dominante/complicaciones , Adolescente , Monitoreo Ambulatorio de la Presión Arterial , Niño , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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 (O2-) 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 O2- (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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Hipertensión/complicaciones , Obesidad/complicaciones , Estrés Oxidativo , Remodelación Ventricular , Adolescente , Adulto , Biomarcadores/sangre , Glucemia , Enfermedades Cardiovasculares/patología , Niño , Humanos , Hipertensión/metabolismo , Insulina/sangre , Metabolismo de los Lípidos , Lípidos/sangreRESUMEN
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/1.73m2 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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Acidosis/epidemiología , Bicarbonatos/sangre , Hiperparatiroidismo Secundario/epidemiología , Insuficiencia Renal Crónica/sangre , Acidosis/sangre , Acidosis/etiología , Adolescente , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Masculino , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Factores de RiesgoRESUMEN
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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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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Lesión Renal Aguda/sangre , Lesión Renal Aguda/complicaciones , Arildialquilfosfatasa/sangre , Asfixia Neonatal/sangre , Asfixia Neonatal/complicaciones , Estrés Oxidativo , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/patología , Área Bajo la Curva , Asfixia Neonatal/enzimología , Asfixia Neonatal/patología , Biomarcadores/sangre , Biomarcadores/metabolismo , Creatinina/sangre , Femenino , Edad Gestacional , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Modelos Logísticos , Masculino , Embarazo , Nacimiento Prematuro , Curva ROC , Ultrasonografía PrenatalRESUMEN
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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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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Puntaje de Apgar , Peso al Nacer/fisiología , Lipoproteínas/sangre , Obesidad Infantil/sangre , Obesidad Infantil/epidemiología , Adolescente , Lactancia Materna/estadística & datos numéricos , Niño , Estudios de Cohortes , Femenino , Humanos , MasculinoRESUMEN
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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Lesión Renal Aguda/etiología , Gripe Humana/complicaciones , Nefritis Intersticial/complicaciones , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Adolescente , Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , Azotemia/etiología , Femenino , Hematuria/etiología , Humanos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/patología , Oseltamivir/uso terapéutico , Prednisona/uso terapéutico , Proteinuria/etiologíaRESUMEN
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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Hipertensión/sangre , Obesidad Infantil/sangre , Adolescente , Biomarcadores/sangre , Niño , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Humanos , Hipertensión/diagnóstico , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Obesidad Infantil/diagnóstico , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Adulto JovenRESUMEN
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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Displasia Fibromuscular/complicaciones , Hipertensión Renovascular/terapia , Obstrucción de la Arteria Renal/complicaciones , Adolescente , Antihipertensivos/uso terapéutico , Niño , Preescolar , Terapia Combinada , Femenino , Displasia Fibromuscular/diagnóstico , Estudios de Seguimiento , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/epidemiología , Hipertensión Renovascular/etiología , Trasplante de Riñón , Masculino , Nefrectomía , Obstrucción de la Arteria Renal/diagnóstico , Estudios Retrospectivos , Serbia/epidemiología , Resultado del TratamientoRESUMEN
The hemolyticuremic 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 522% 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 35%. 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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Infecciones por Escherichia coli/diagnóstico , Infecciones por Escherichia coli/terapia , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/terapia , Escherichia coli Shiga-Toxigénica , Infecciones por Escherichia coli/complicaciones , Síndrome Hemolítico-Urémico/epidemiología , Síndrome Hemolítico-Urémico/microbiología , HumanosRESUMEN
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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Lesión Renal Aguda/diagnóstico , Asfixia Neonatal/complicaciones , Enfermedades del Prematuro/sangre , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Proteínas de Fase Aguda , Área Bajo la Curva , Asfixia Neonatal/sangre , Biomarcadores/sangre , Estudios Transversales , Diagnóstico Precoz , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/diagnóstico , Unidades de Cuidado Intensivo Neonatal , Lipocalina 2 , Masculino , Selección de Paciente , Curva ROC , Sensibilidad y Especificidad , SerbiaRESUMEN
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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Lesión Renal Aguda/economía , Procedimientos Quirúrgicos Cardíacos/economía , Modelos Económicos , Complicaciones Posoperatorias/economía , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Proteínas de Fase Aguda/orina , Adolescente , Biomarcadores/sangre , Biomarcadores/orina , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Estudios de Casos y Controles , Niño , Preescolar , Costos y Análisis de Costo , Cistatinas/sangre , Femenino , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/orina , Humanos , Lactante , Lipocalina 2 , Lipocalinas/orina , Masculino , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/orina , Proteínas Proto-Oncogénicas/orinaRESUMEN
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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Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Recien Nacido con Peso al Nacer Extremadamente Bajo , Glicoproteínas de Membrana/orina , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Biomarcadores/sangre , Biomarcadores/orina , Peso al Nacer , Creatinina/sangre , Femenino , Edad Gestacional , Receptor Celular 1 del Virus de la Hepatitis A , Mortalidad Hospitalaria , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Modelos Lineales , Modelos Logísticos , Oportunidad Relativa , Mortalidad Perinatal , Valor Predictivo de las Pruebas , Embarazo , Pronóstico , Estudios Prospectivos , Receptores Virales , Factores de Riesgo , UrinálisisRESUMEN
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.
Asunto(s)
Sistema Urinario/crecimiento & desarrollo , Trastornos Urinarios , Micción/fisiología , Humanos , Trastornos Urinarios/diagnóstico , Trastornos Urinarios/etiología , Trastornos Urinarios/fisiopatologíaRESUMEN
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.
Asunto(s)
Estudios de Asociación Genética , Péptidos y Proteínas de Señalización Intracelular/genética , Laminina/genética , Proteínas de la Membrana/genética , Síndrome Nefrótico/genética , Edad de Inicio , Análisis Mutacional de ADN , Femenino , Genes del Tumor de Wilms , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Síndrome Nefrótico/mortalidad , PronósticoRESUMEN
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.
Asunto(s)
Infecciones Urinarias/microbiología , Amoxicilina/farmacología , Cefalosporinas/farmacología , Farmacorresistencia Bacteriana , Enterococcus/aislamiento & purificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Europa (Continente) , Humanos , Lactante , Riñón/anomalías , Klebsiella/aislamiento & purificación , Nitrofurantoína/farmacología , Estudios Prospectivos , Proteus/aislamiento & purificación , Pseudomonas/aislamiento & purificación , Encuestas y Cuestionarios , Trimetoprim/farmacología , Orina/microbiologíaRESUMEN
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.