Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children.

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.

Subclinical atherosclerosis and ambulatory blood pressure in children with metabolic syndrome.

BACKGROUND: The metabolic syndrome (MS) has reached epidemic proportions worldwide. This syndrome is associated with cardiovascular risk factors, including functional and structural cardiac and vascular changes. The aim of our study was to evaluate subclinical atherosclerosis and its associated risk factors in children with MS. METHODS: The study cohort comprised 52 children with MS and 38 age- and sex-matched healthy children. The diagnosis of MS was made according to criteria adopted by the World Health Organization. Blood pressure based on 24-h ambulatory blood pressure monitoring (ABPM), carotid intima-media thickness (cIMT), carotid distensibility coefficient (DC) and flow-mediated endothelium-dependent dilation (EDD) were assessed in all children. RESULTS: We found a significantly higher cIMT in children with MS than in healthy children, but carotid DC and flow-mediated EDD were lower in the former. Multivariate analysis revealed that a higher cIMT was independently associated with a higher nighttime systolic blood pressure (SBP) and lower high-density lipoprotein-cholesterol (ß = 0.386, p = 0.011 and ß = 0.248, p = 0.042, respectively). Also, higher nighttime SBP remained an independent predictor of lower DC (ß = 0.495, p = 0.009), and higher 24-h SBP was the only independent predictor for a lower EDD (ß = 0.532, p = 0.004). CONCLUSIONS: Atherosclerotic vascular changes were common among our pediatric patients with MS and easily determined by high-resolution ultrasound imaging. In particular, subclinical atherosclerosis was clearly associated with nocturnal or 24-h systolic hypertension as measured by ABPM. We therefore recommend that subclinical vascular changes and AMBP measurements should be used as diagnostic markers to predict atherosclerotic risks in this pediatric patient group.

Ambulatory blood pressure monitoring and cardiac hypertrophy in children with metabolic syndrome.

BACKGROUND: The metabolic syndrome (MS), a cluster of potent risk factors for cardiovascular disease, is composed of insulin resistance, obesity, hypertension and hyperlipidemia. The aim of our study was to investigated the relationships between MS and left ventricular mass index (LVMI) in childhood MS. This study included 50 children and adolescents with MS aged between 7-18 years. METHODS: Thirty age- and sex-matched healthy children served as a control group. The diagnosis of MS was made according to the criteria adapted from the World Health Organization. They underwent clinical examination with causal blood pressure (BP) measurements, 24-hour ambulatory blood pressure monitoring (ABPM) and echocardiogram. Patients underwent echocardiography to detect left ventricular hypertrophy (LVH). LVMI was calculated as left ventricular mass/height(2.7). RESULTS: The mean age of MS group was 12.0 ± 3.1 years. The mean value of LVMI was 46.5 ± 11.5 g/m(2.7) in the MS group and it was significantly higher than those in the healthy children. The prevalence of severe LVH was 12 % using adult criteria (LVM > 51 g/m(2.7)) and 44 % using pediatric criteria (LVM > 95th percentile). The mean daytime systolic BP load (ß = 0.315, p = 0.003) and HOMA-IR (ß = 0.368, p = 0.006) were found as the independent predictors of LVMI. CONCLUSIONS: In conclusion, LVH occurs commonly in pediatric MS and is associated with systolic hypertension and insulin resistance. LVMI should be measured routinely for the predicting of cardiovascular risks in these patients.

Glucose intolerance: is it a risk factor for cardiovascular disease in children with chronic kidney disease?

A total of 66 children and adolescents with chronic kidney disease (CKD) (20 pre-dialysis patients and 46 chronic dialysis patients) were evaluated to address the prevalence of abnormalities in glucose and insulin metabolism and their association with cardiovascular disease. Glucose intolerance was assessed using an oral glucose tolerance test; insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). Carotid artery intima-media thickness (IMT) and left ventricular hypertrophy (LVH) were examined as early markers of cardiovascular disease. Thirty-four patients (7 pre-dialysis, 27 dialysis) exhibited an abnormal glucose tolerance; however, ten patients (7 pre-dialysis, 3 dialysis) were insulin-resistant. Height-specific standard deviation scores of carotid artery IMT were above normal in three of the pre-dialysis patients (15%) and in 34 of the dialysis patients (74%). LVH was present in seven pre-dialysis (35%) and 34 dialysis patients (74%). In addition, two of the pre-dialysis patients (10%) and 18 of the dialysis patients (39%) had severe LVH. The prevalence of both increased carotid artery IMT and LVH were similar in patients with or without glucose intolerance in both groups, but severe LVH was more prevalent in pre-dialysis patients with glucose intolerance (p = 0.042). The multivariate analyses showed that neither carotid artery IMT nor LVM index was predicted by serum glucose levels or HOMA-IR. In conclusion, children with CKD are at a high risk of glucose intolerance and also have a greater risk of subclinical cardiovascular disease (CVD). However, the presence of glucose intolerance does not appear to be an independent risk factor for increased carotid artery IMT or LVH.

Elevated plasma advanced oxidation protein products in children with Henoch-Schonlein purpura.

Henoch-Schonlein purpura (HSP) is a systemic vasculitis characterized by involvement of skin, joints, gastrointestinal tract (GIT), and kidney; its pathogenesis is still controversial. The aim of our study was to investigate the role of oxidative stress in the pathogenesis of HSP. Plasma advanced oxidation protein products (AOPP) level was measured in 29 children with HSP at the onset of the disease and during remission in comparison with 30 healthy subjects. Patients at the active stage had significantly higher AOPP levels than those at the remission stage of HSP and the controls (42.9 ± 25.7, 30.6 ± 11.8, 27.9 ± 11.2 mmol/l; P = 0.027 and P = 0.023 respectively). The mean AOPP levels of the patients with arthritis and/or arthralgia were significantly higher those than without joint involvement (48.3 ± 26.0 and 22.3 ± 9.3, P = 0.036 respectively). However, AOPP levels were similar in patients with and without gastrointestinal involvement. Plasma AOPP levels were positively correlated with leukocyte and thrombocyte count at disease onset, whereas they were found to be negatively correlated with serum glucose and sodium levels. The mean thrombocyte count was the only independent predictor of increased level of AOPP in regression analysis (ß = 0.407; P = 0.029). In conclusion, this study showed that increased oxidative stress may play an important role in the pathogenesis of HSP. Also, we suggest that higher platelet count might be an indirect indicator of oxidative stress in these patients. Further research is required to identify the potential association between oxidative stress and increased thrombocyte count in children with HSP.

Dialysate CA125 levels after 5 years on continuous peritoneal dialysis.

The aim of this study was to evaluate longitudinal changes in dialysate cancer antigen 125 (dCA125) levels over time and to analyze relationships between dCA125 and peritoneal glucose exposure (PGE) in children undergoing long-term peritoneal dialysis (PD). The study group included seven boys and four girls (mean age 13 ± 5.1 years) with a mean PD duration of 84.0 ± 1.1 months. A peritoneal equilibration test (PET) was performed, and dCA125 levels were measured in all patients. Peritoneal appearance rates (AR) of dCA125, the velocity of the decrease in dCA125AR values, and annual PGE levels were also calculated. The final tests were performed at a mean of 63.3 ± 3.5 months after the initial ones. Both dCA125 and dCA125AR levels showed statistically significant decrements during the follow-up period (p = 0.003), with the velocity of decrease in dCA125AR found to be 52.6 ± 19.4%. There were no significant differences in peritoneal transport parameters between the beginning and end of the study period. PGE values were significantly higher in the last year of the study than in the first year (p = 0.014), but the velocity of the decrease in dCA125AR levels was not related to total PGE. In conclusion, a significant decline was found in dCA125 and CA125 AR levels, reflecting mesothelial cell mass, in children undergoing long-term PD (>5 years), but these were not related to PGE.

Cord blood antibody following maternal SARS-CoV-2 inactive vaccine (CoronaVac) administration during the pregnancy.

Maternal vaccination with SARS-CoV-2 vaccines has not been well studied yet in terms of safety and efficacy for protecting the newborn by the placental passage of antibodies. We reported 34 years of old health care worker (HCW) without any known SARS-CoV-2 infection. She had the first dose of SARS-CoV-2 inactivated virus vaccine (CoronaVac, Sinovac Life Science Co, Ltd, Beijing, China) at a gestational age of 28 weeks. The second dose of vaccine was given four weeks later at a gestational age of 32 weeks. HCW did not report any vaccine-related adverse events after either the first or second dose of the vaccine. Three weeks after the second dose of the vaccine, her anti-receptor-binding domain (RBD) of SARS-CoV-2 spike protein antibody was 779 arbitrary units (AU) per ml. She gave a birth of 38 weeks three days gestation age of healthy, full-term girl with a birth weight of 2770 gr. The mother's anti-RBD antibody was 734 AU/ml, the infant's cord blood anti-RBD antibody level was 764 AU/ml, respectively, cord sera/maternal sera transfer ratio was 1,04. This infant is the first identified case of SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination with CoronaVac.

Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers.

The effects of inactivated SARS-CoV-2 vaccine (CoronaVac) on previously naturally infected individuals are unknown. This study compared immunogenicity and reactogenicity of CoronaVac in once naturally infected health-care workers (HCWs) and uninfected HCWs. All HCWs were immunized with two doses of CoronaVac (600 U/0.5 ml) intramuscularly at a 28-day interval. Adverse reactions were obtained by web-based questionnaires or telephone calls seven days after each vaccine dose. Detection of antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was done four weeks after the second dose of the vaccine. We enrolled 103 previously naturally infected and 627 uninfected HCWs. The mean time for vaccination after the first nasopharyngeal SARS-CoV-2 positivity was 64 days (range: 15-136 days) in previously naturally infected HCWs. Among the previously naturally infected HCWs, 41 (40%) were asymptomatic, 52 (50%) had mild upper respiratory tract infections, 10 (105) had pneumonia, and only 6 (5%) were hospitalized. Any reported adverse reactions, either from the first dose or the second dose of vaccine administration, did not differ between previously infected and uninfected HCWs. Anti-RBD antibody titers were obtained in 50 (51%) of 103 previously infected HCWs and 142 (23%) of 627 uninfected HCWs. Anti-RBD antibody titers were significantly higher in HCWs with a previous natural infection (median 1220 AU/ml, range: 202-10328 AU/mL) than in uninfected HCWs (median: 913 AU/ml, range: 2.8-15547 AU/mL, p = .032). CoronaVac administration was safe and may elicit higher antibody responses in previously naturally infected individuals.

Assessment of cardiovascular risk in paediatric peritoneal dialysis patients: a Turkish Pediatric Peritoneal Dialysis Study Group (TUPEPD) report.

METHODS: We aimed to clarify arteriosclerotic risk and to document possible relationships between cardiovascular risk factors and echocardiographic parameters in paediatric peritoneal dialysis (PD) patients. M-mode/Doppler/tissue Doppler echocardiographic studies and lipid/lipoproteins, homocysteine, high-sensitivity C-reactive protein (HS-CRP) levels and carotid intima-media thickness (CIMT) were determined in 59 patients (age: 14.2 +/- 4.5 years) and in 36 healthy subjects. RESULTS: Structural and functional cardiac abnormalities were observed in patients on maintenance dialysis. Increased left ventricular mass index (LVMI, P = 0.000), relative wall thickness (P = 0.000), myocardial performance index (MPI, P = 0.000) were documented in the patients. Lipoprotein (a) (P = 0.000), homocysteine (P = 0.001), HS-CRP (P = 0.000) and CIMT (P = 0.000) were significantly elevated in the patients. Left ventricular hypertrophy (LVH) was prevalent in 68% of the patients. Patients with LVH had higher levels of HS-CRP (P = 0.001) and CIMT (P = 0.028) than those without LVH. Haemoglobin was an independent predictor of LVMI (beta: -8.9, P = 0.001), while residual diuresis and CIMT were independent predictors of diastolic dysfunction (beta: -0.45, P = 0.034 and beta: 5.90, P = 0.008, respectively). Albumin (beta: -0.72, P = 0.018) and Kt/V urea (beta: -0.48, P = 0.012) were significant predictors of CIMT. There were positive correlations between LVMI and CIMT. HS-CRP was positively correlated with LVMI as well as CIMT. CONCLUSIONS: Elevated levels of atherosclerotic/ inflammatory risk factors, low haemoglobin levels and loss of residual renal function and their negative effects on heart are of remarkable importance in paediatric patients on maintenance peritoneal dialysis. Achieving recommended targets for haemoglobin, blood pressure and Kt/V urea, preserving residual renal function as well as managing inflammation and subsequent arteriosclerosis is obviously essential to improve the patients' prognosis.

Left ventricular function by 'conventional' and 'tissue Doppler' echocardiography in paediatric dialysis patients.

AIM: Cardiovascular abnormalities are common in children with chronic kidney disease (CKD). Left ventricular (LV) structure and functions have been extensively studied by conventional pulse-wave Doppler echocardiography (cPWD), however, tissue Doppler imaging (TDI) is a relatively new echocardiography method. The aims of this study were to evaluate LV diastolic function in paediatric dialysis patients using cPWD and TDI methods, and to compare the findings obtained with two modalities. METHODS: This study included 38 children and adolescents on dialysis (14 haemodialysis and 24 peritoneal dialysis, duration of dialysis 58.0 +/- 32.8 months) and 16 age- and sex-matched healthy subjects. RESULTS: The mean left ventricular mass index (LVMI) was significantly higher in the patient group (P < 0.001) and the most common cardiac geometry was concentric LV hypertrophy (55%). There was no significant difference in LV systolic function between patient and control groups. However, dialysis patients had worse LV diastolic function both according to cPWD (lower E/A ratio) and TDI (lower Em/Am ratio) than the healthy subjects (P < 0.001 and P = 0.001, respectively). Also, the index of LV filling pressure (E/Em ratio) obtained by the combination of cPWD and TDI was significantly higher in the patients (P < 0.001). Cumulative dose of calcium-based phosphate binder (CBPB), diastolic blood pressure and LVMI were the independent predictors of E/Em ratio. CONCLUSION: Our study shows that LV diastolic dysfunction is common in paediatric dialysis patients and TDI findings correlate well with cPWD findings. Similarly, higher dose intake of CBPB, hypertension and LV hypertrophy have a negative effect on LV filling pressure suggesting diastolic function.

Coinheritance of sickle cell anemia and hereditary spherocytosis.

To date only three siblings with coinheritance of sickle cell anemia (SCA) and hereditary spherocytosis (HS) have been reported. We here describe a 17-year-old boy who experienced episodes of hemolysis and had a large spleen. The diagnosis of SCA was confirmed by hemoglobin electrophoresis (HbS 88.9%) and genetic analysis (homozygote HbSS mutation). The diagnosis of HS was established by an osmotic fragility test, performed twice. A splenectomy was performed, and following surgery the hemoglobin concentration was maintained between 9 and 11 g/dl without further transfusion requirements. This patient was the fourth reported case with co-existence of two different genetically transmitted hemolytic anemias.

A case of catastrophic antiphospholipid syndrome in an adolescent girl with parvovirus B19 infection.

Antiphospholipid syndrome is an autoimmune disease characterized by recurrent thrombosis and the presence of antiphospholipid antibodies. Clinical presentations are dependent on the affected vessels and organs. The most common presentation of antiphospholipid syndrome is arterial or venous thrombosis. An unusual presentation of the disease is characterized by microvascular thrombosis with multiorgan involvement, which is termed catastrophic antiphospholipid syndrome. The diagnosis of catastrophic antiphospholipid syndrome can be difficult because of the heterogeneity of the different clinical forms. Clinical manifestations of catastrophic antiphospholipid syndrome are complex with multiple organ involvement, resulting in renal insufficiency, heart failure, acute respiratory distress syndrome, and liver involvement. Early diagnosis and aggressive therapies are essential in this condition because of the extremely high mortality rate. Herein, the case of a 14-year-old girl with catastrophic antiphospholipid syndrome that was previously misdiagnosed as a vasculitis related to parvovirus B19 infection is presented.

A child with primary Sjögren syndrome and a review of the literature.

Primary Sjögren syndrome (pSS) is an uncommon disease in childhood. Childhood pSS might have different clinical manifestations than adult pSS. We describe a 13-year-old girl with multiple episodes of bilateral parotid swelling lasting 2 years. Her history included severe arthralgia, local edema, and purpura episodes since 9 years of age. During her 3-week hospitalization, 2 episodes of parotid swelling occurred, which both resolved in 48 hours. Ultrasonography and magnetic resonance images of parotid glands showed parenchymal inhomogeneity related to adipose degeneration and nodular pattern. Investigations showed elevated erythrocyte sedimentation rate, the presence of hypergammaglobulinemia, positive antinuclear antibody, and elevated rheumatoid factor, anti-Sjögren syndrome antigen A, and anti-Sjögren syndrome antigen B. Histopathologic examination of labial minor salivary glands revealed focal periductal lymphocytic infiltrate and sialoduct ectasia. She was diagnosed as having pSS. Recurrent parotid swelling is a more characteristic feature of disease in children, and this finding should alert the clinician to the possible diagnosis of pSS.

Control of bleeding associated with hemophagocytic syndrome in children: an audit of the clinical use of recombinant activated factor VII.

This paper presents 2 cases of hemophagocytic lymphohistiocytosis (HLH) in whom recombinant factor VIIa (rFVIIa) was used for the management of hemorrhage. Both patients were diagnosed as HLH and were bleeding from the gut, which could not be controlled. Patients received rFVIIa at total doses of between 90 and 180 microg/kg body weight. Hemostatic affect was achieved in both of the patients but lasted only a short time. The response was achieved after 1 h of administration of rFVIIa, lasting for 24 h. The use of rFVIIa was well tolerated. These 2 patients suggest that rFVIIa is a beneficial agent in the management of hemorrhage in patients with HLH, although for a permanent homeostasis the control of primary disease is essential.

Hypo- and hypervolemic edema in children with steroid sensitive nephrotic syndrome.

BACKGROUND/AIM: The mechanism of edema formation in nephrotic syndrome is still poorly understood. We aimed to evaluate the volume status in children with steroid-sensitive nephrotic syndrome (SSNS) and to emphasize the importance of echocardiography in demonstrating of volume changes. MATERIALS AND METHODS: Thirty-two SSNS patients and 30 healthy children were enrolled in this study. The volume statuses of patients were evaluated by clinical and laboratory features, including fractional sodium excretion (FENa) and distal sodium/potassium exchange (UK/UNa+K ratio). Inferior vena cava collapsibility index (IVCCI), left atrial diameter (LAD), aortic diameter (AD), and left ventricular mass index (LVMI) were measured using conventional echocardiographic methods. RESULTS: FENa was lower in children with NS; however, the distal K/Na ratio of the patient and control groups did not differ. In addition, IVCCI, LAD, AD, and LVMI were not different among groups. When evaluating the volume status of patients, 8 patients (25%) were hypovolemic while 24 patients (75%) were nonhypovolemic (normovolemic or hypervolemic). LAD was significantly lower in hypovolemic patients. CONCLUSION: The majority of children with SSNS are normovolemic or hypervolemic and echocardiography is an easy and valuable method for the evaluation of volume status in these patients.

Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus type 1 is the most common endocrine metabolic disorder occurring in childhood and adolescence due to the autoimmune destruction of pancreatic beta cells as a result of various environmental factors interacting with an underlying genetic predisposition. Diabetes is a risk factor for early onset atherosclerosis, and the high mortality rate seen in these patients is partially related to cardiovascular diseases. OBJECTIVES: This study was conducted to compare mean platelet volume as a marker of early atherosclerosis with aortic intima-media thickness in children with type 1 diabetes and to identify its correlation with known cardiovascular risk factors. PATIENTS AND METHODS: The study included 27 patients between age range of 6 and 17 years that were diagnosed with type 1 diabetes and 30 healthy children of the same age range who did not have any chronic disease. In both groups, we used the color Doppler ultrasound to measure children's aortic intima-media thickness and identify their mean platelet volumes. RESULTS: There was no significant difference between the groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant difference could be documented between the patient and control groups regarding the aortic intima-media thickness and mean platelet volume (P > 0.05). However, there was a significant correlation between aortic intima-media thickness and mean platelet volume (r = 0.351; P < 0.05). CONCLUSIONS: In the present study, there was no evidence of early atherosclerosis in children with type 1 diabetes. However, mean platelet volume having a significant correlation with aortic intima-media thickness may be useful as an early marker of atherosclerosis.