High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

AbstractBackground: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-en..

Improving the diagnosis of X-linked hypophosphatemia: recommendations to optimize diagnostic flow and clinician/geneticist cooperation in the Italian clinical practice

Objective: To provide Italian expert opinion-based practical recommendations to improve the cooperation between clinicians and geneticists in order to optimize diagnostic flow and care of X-linked hypophosphatemia (XLH). Methods: A panel of four geneticists and four clinicians from Italian reference centers for the diagnosis and management of XLH met virtually, first to highlight the critical issues in patient care and then to identify and share proposals to improve the diagnostic and care path of XLH. Results: Critical issues emerged regarding the transfer of adequate clinical information from clinicians to geneticists, standardization and clarity of genetic reporting, and adequate interactions between clinicians and geneticists during patients' follow-up. The necessary requirements for an appropriate request for evaluation of genetic variants and the need for a clear and clinically useful genetic report were agreed upon. Specifically designed template forms to be adopted with appropriate adjustments were defined and are here proposed for both the clinician's request and the geneticist's report. Conclusions: The expert group strongly believes that collaboration between clinicians and geneticists should be encouraged in XLH, not only in the diagnostic phase but also during a patient's follow-up, in order to manage patients more comprehensively and effectively

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function

Use of Melatonin in Oxidative Stress Related Neonatal Diseases

Reactive oxygen species have a crucial role in the pathogenesis of perinatal diseases. Exposure to inflammation, infections, or high oxygen concentrations is frequent in preterm infants, who have high free iron levels that enhance toxic radical generation and diminish antioxidant defense. The peculiar susceptibility of newborns to oxidative stress supports the prophylactic use of melatonin in preventing or decreasing oxidative stress-mediated diseases. Melatonin, an effective direct free-radical scavenger, easily diffuses through biological membranes and exerts pleiotropic activity everywhere. Multiple investigations have assessed the effectiveness of melatonin to reduce the “oxygen radical diseases of newborn” including perinatal brain injury, sepsis, chronic lung disease (CLD), and necrotizing enterocolitis (NEC). Further studies are still awaited to test melatonin activity during perinatal period

Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1

Background: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. Methods: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). Results: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8–14.3) versus 5.9 (5.2–6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (β = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. Conclusions: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up

Time of Onset and Risk Factors of Renal Involvement in Children with Henoch-Schönlein Purpura: Retrospective Study

Background: Henoch-Schönlein purpura (HSP) is a common systemic vasculitis in children, involving the skin, musculoskeletal system, gastrointestinal tract and kidneys. Some studies in children have shown possible risk factors linked with the development and severity of HSP Nephritis (HSPN). The aim of this study was to research predicting factors for the development of HSPN. Methods: We retrospectively evaluated 132 pediatric patients with HSP, according to EULAR/PRINTO/PRESS criteria. All patients were screened for HSPN by urinalysis. Finally, we compared demographic, clinical and laboratory data in HSP patients with and without nephritis. Results: The median age at HSP diagnosis [6.2 (2.6–17.5) vs. 5.5 (0.8–15.4) years, p = 0.03] and the incidence of abdominal pain (48 vs. 27%, p = 0.01) were significantly higher in HSPN patients. No differences were evidenced regarding gender, allergic diseases, skin recurrences, gastrointestinal involvement, musculoskeletal involvement, scrotal involvement, and laboratory data (white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein, erythrocyte sedimentation rate, and blood concentration of IgA). Conclusions: The age at diagnosis and abdominal pain were independent risk factors for renal involvement in HSP patients. However, due to the retrospective nature of this study, further long-term and prospective studies will be necessary

Peritoneal dialysis in infants: the experience of the Italian Registry of Paediatric Chronic Dialysis

Although chronic peritoneal dialysis (CPD) is considered the replacement therapy of choice for infants with end-stage renal failure, many questions persist about treatment risks and outcomes

Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis

The clinical syndrome idiopathic intracranial hypertension (IIH), also termed pseudotumor cerebri, consists of symptoms of headache, nausea, vomiting and visual field defects in combination with findings of papilledema. IIH is more commonly seen in overweight women where the rise in intracranial pressure is putatively a consequence of an endocrine-based disturbance of electrolytes. Less frequently, it can also occur in men and in the pediatric age group. Associated risk factors include primary and secondary aldosteronism, pregnancy, recombinant growth hormone (r-GH) therapy, oral contraceptives, obesity, vitamin A intoxication or deficiency, Addison disease, corticosteroid therapy or acute withdrawal of steroid therapy and Cushing disease. Herein, we review the association between these conditions and IIH working toward its having a unifying neuroendocrine hypothesis

Update on the Classification and Pathophysiological Mechanisms of Pediatric Cardiorenal Syndromes

Cardiorenal syndrome (CRS) is defined as a disorder resulting from the abnormal interaction between the heart and kidney, in which acute or chronic dysfunction of one organ may lead to acute and/or chronic dysfunction of the other. The functional interplay between the heart and kidney is characterized by a complex bidirectional symbiotic interaction, regulated by a wide array of both genetic and environmental mechanisms. There are at least five known subtypes of CRS, based on the severity of clinical features and the degree of heart/renal failure. The fourth subtype (cardiorenal syndrome type 4 (CRS4)) is characterized by a primary chronic kidney disease (CKD), which in turn leads to a decreased cardiac function. Impairment of renal function is among the most important pathophysiological factors contributing to heart failure (HF) in the pediatric age group, and cardiovascular complications could be one of the most important causes of mortality in pediatric patients with advanced CKD. In this context, a loss of glomerular filtration rate directly correlates with both the progression of cardiovascular complications in CRS and the risk of HF. This review describes the interaction pathways between the heart and kidney and the recently identified pathophysiological mechanisms underlying pediatric CRS, with a special focus on CRS4, which encompasses both primary CKD and cardiovascular disease (CVD)

Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis

Paediatric literature about encapsulating peritoneal sclerosis (EPS) is limited and comes primarily from anecdotic experiences. In this study, we described the incidence and characteristics of EPS in a large paediatric chronic peritoneal dialysis (CPD) patient population