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Objective: Non-alcoholic fatty liver disease (NAFLD) negatively impacts on renal function with the contribution of the I148M variant in the patatin like phospholipase containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148M PNPLA3 polymorphism on the relationship between eGFR and prediabetes in children with obesity. Methods: One thousand thirty-six children underwent to complete assessment and were genotyped for the I148M PNPLA3 polymorphism. Results: Patients with prediabetes showed lower eGFR levels (171.03±40.32 vs. 190.80±41.71ml/min/1.73 m2; p=0.001) and higher prevalence of NAFLD (80% vs. 59%; p=0.003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97±14.56 vs 192.88±40.09; p

In youths, two cut-offs (133 and 155 mg/dL) have been proposed to identify high glucose levels at the 1 h (G60) mark during an oral glucose tolerance test (OGTT). We evaluated which cut-off was more closely associated with isolated impaired glucose tolerance (IGT) and cardiometabolic risk (CMR) in 1199 youth with overweight/obesity (OW/OB) and normal fasting glucose and/or HbA1c. The disposition index (DI) was available in 724 youths. The sample was divided by two cut-offs of G60

In 2020, an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease (MAFLD). This recent proposal reflects the close association of fatty liver with metabolic derangements, as demonstrated by previous robust data. Several factors [including genetics, inflammation, metabolic abnormalities, insulin resistance (IR), obesity, prenatal determinants, and gut-liver axis] have been found to be involved in MAFLD pathophysiology, but this tangled puzzle remains to be clearly understood. In particular, IR has been recognized as a key player in metabolic impairments development in children with fatty liver. On this ground, MAFLD definition focuses on the pathophysiological basis of the disease, by emphasizing the crucial role of metabolic impairments in this condition. Although primarily developed for adults, MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles, because of the increasing attention to cardiometabolic risk in childhood. To date, accumulating evidence is available on the feasibility of MAFLD definition in clinical practice, but some data are still conflicting in highly selected populations. Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk, early strategies for MAFLD identification, treatment and prevention are needed. Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging. We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.

Foreign body aspiration is common in the pediatric age group, especially in males. Despite the high frequency of this potentially life-threatening event, it is not always easy to recognize it given the high variability of the clinical presentation and the potential of “pauci-symptomatic” inhalation. Moreover, a variable latency of the onset of symptoms since the moment of aspiration may be possible determining difficulties in the identification of the inhalation on an anamnestic basis. We describe the case of a 19-month-old boy who accessed the emergency room initially for a head trauma. The clinical evaluation, however, revealed an unexplained serious respiratory distress needing tracheal intubation. After our evaluation, we hypothesized that the severe respiratory distress determined an altered state of consciousness with following head trauma. The radiological findings raised the suspicion of foreign body aspiration for the presence of an atelectasis of the entire left lung. The computed tomography showed an abrupt interruption of the main bronchus at 12 mm from the hull. The following bronchoscopy identified an almond of 2 cm. We will review the literature to underline the diagnostic issues behind foreign body aspiration in children by highlighting the diagnostic clues that are helpful for emergency clinicians in the management of this condition.

The aim of the study was to evaluate whether serum aldosterone levels or plasmatic renin activity (PRA) measured early in life (1–3 months) could predict a future surgical intervention for obstructive congenital anomalies of kidney and urinary tract (CAKUT). Twenty babies aged 1–3 months of life with suspected obstructive CAKUT were prospectively enrolled. The patients underwent a 2-year follow-up and were classified as patients needing or not needing surgery. In all of the enrolled patients, PRA and serum aldosterone levels were measured at 1–3 months of life and were evaluated as predictors of surgery by receiver-operating characteristic (ROC) curve analysis. Patients undergoing surgery during follow-up showed significantly higher levels of aldosterone at 1–3 months of life compared to those who did not require surgery (p = 0.006). The ROC curve analysis of the aldosterone for obstructive CAKUT needing surgery showed an area under the ROC curve of 0.88 (95%CI = 0.71–0.95; p = 0.001). The aldosterone cut-off of 100 ng/dL presented 100% sensitivity and 64.3% specificity and predicted surgery in 100% of cases. The PRA at 1–3 months of life was not a predictor of surgery. In conclusion, serum aldosterone levels at 1–3 months could predict the need for surgery during obstructive CAKUT follow-up.

Background The main purpose of the study is to assess the association between obstructive sleep apnea (OSA) and insulin secretion in children with obesity. Methods We enrolled children and adolescents who attended our pediatric clinic because of obesity and OSA. Glucose homeostasis was assessed through standard 2-h oral glucose tolerance test (OGTT). Nocturnal cardio-respiratory polygraphy was performed for OSA diagnosis. Twenty-two patients underwent a 3-h OGTT to investigate insulin secretion and sensitivity through the oral-minimal model. Results seventy-seven children and adolescents were included in the study. Based on OSA severity, the cohort was divided into three groups (29 mild, 29 moderate, and 19 severe OSA). The group with mild OSA showed lower levels of 30-min glucose (p = 0.01) and 60-min glucose (p = 0.03), and lower prevalence of elevated 1-h glucose (10.4% versus 44.8% in moderate and 31.6% in severe OSA, p = 0.01). The odds for elevated 1-h plasma glucose was 6.2-fold (95%CI 1.6–23.4) higher in subjects with moderate and severe OSA compared to mild OSA (p = 0.007) independent of confounders. Spearman correlation test revealed a positive correlation between 30-min plasma glucose and apnea-hypopnea index (AHI, r = 0.31, p = 0.01), oxygen desaturation index (ODI, r = 0.31, p = 0.009), and mean desaturation (r = 0.25, p = 0.04). The 3-h OGTT study included 22 participants (7 mild, 9 moderate, and 6 severe OSA). The group with mild OSA showed a higher dynamic, static, and total insulin secretion compared to those with moderate and severe OSA (p p = 0.007, p = 0.007, respectively). AHI was significantly correlated to dynamic insulin secretion (r = −0.48, p = 0.02). Conclusions OSA might impair beta-cell function reducing the pool of promptly releasable insulin in children and adolescents with obesity, in the absence of an effect on insulin sensitivity.

Objective To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage. Methods A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate 2%. ATN was defined by RTD+AKI. Results Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared. Conclusions ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI. Impact This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants.

This cross-sectional study aimed to assess the best cut-off of HbA1c for detection of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), beta-cell impairment and cardiometabolic risk (CMR) profile in overweight or obese (OW/OB) Caucasian youths. Two-hour oral glucose tolerance test was available in 1549 youths, one-hour glucose (G60) in 1430 youths and disposition index (DI) in 972 youths. Insulin resistance (IR) was calculated as Homeostatic Model Assessment for IR and insulin sensitivity (IS) as 1/fasting insulin. High G60 was defined by a value ≥ 133 mg/dL. The best cut-off of HbA1c for IFG or IGT was 5.5%. The frequency of individuals with HbA1c ≥ 5.5% was 32.5%, compared to 16.3% with HbA1c ≥ 5.7% (as proposed by the American Diabetes Association). HbA1c ≥ 5.5% showed higher sensitivity and lower specificity with respect to HbA1c ≥ 5.7% for all the abnormalities examined (IFG, IGT, high G60, IR, low IS, DI and CMR factors). In conclusion, this lower cut-off might represent a more appropriate screening marker of glucose dysmetabolism in youths with OW/OB. Prospective studies are needed to validate this cut-off for predicting prediabetes/diabetes in youths with OW/OB.

The coronavirus disease 2019 (COVID-19) pandemic changed adults and children’s lifestyle. We focused our attention on children affected by chronic kidney disease (CKD) due to congenital abnormalities of kidney and urinary tract (CAKUT) and their behavior during the lockdown. Our aims were to evaluate the incidence of CKD progression within 6 months after the end of the first Italian lockdown and the factors associated to it. CKD progression was defined by the transition to higher CKD stage or by the drop in estimated glomerular filtration rate by a 25% or more for patients belonging to CKD stages 1 and 2. We retrospectively selected 21 children with CAKUT and CKD ≥ stage 1 observed within 3 months before and 6 months after the first Italian lockdown. We called them by phone and asked them about their lifestyle before and during lockdown focusing on physical activity, screen time, sweet/candies/sugar-sweetened beverages eaten/drunk and adherence to the Mediterranean diet (MD) (through KIDMED questionnaire). We calculated and analyzed the delta between the pre- and post- lockdown observation of all collected parameters (clinical and biochemical parameters and questionnaires scores). Analyzing the overall cohort, we found significantly increased mean BMI and mean screen time and significantly lower mean physical activity time in post- compared with pre-lockdown observations. Eleven out of twenty-one patients (52.4%) had a worsening of CKD. These patients presented higher delta of levels of uric acid and microalbuminuria and showed minor adherence to the MD and declared to have consumed more sweets or candies or sugar-sweetened beverages/week during the lockdown with a tendentially major increment of BMI compared with patients not presenting CKD progression. In conclusion, the lockdown for COVID-19 pandemic determined increase of BMI in all enrolled patients due to a “forced” negative lifestyle. About half of these patients presented CKD progression. This progression was associated to less adherence to the MD and major consumption of sweets or candies or sugar-sweetened beverages.

Lower urinary tract symptoms (LUTS) are a relevant problem in the pediatric population, having a very high prevalence. Diurnal incontinence and nocturnal enuresis are surely the most frequent symptoms, presenting, respectively, in up to 30% of school-age children and up to 10% of children between 6 and 7 years. Stypsis is the most common comorbidity, and it must be considered in the management of LUTS; indeed, the treatment of constipation is curative in most cases for both incontinence and enuresis. The presence or absence of diurnal symptoms in nocturnal enuresis and urgency in diurnal incontinence helps in the differential diagnosis. Urotherapy is always the first-line treatment, while oxybutynin and desmopressin (where appropriate) may help if the first-line treatment is unsuccessful. It is essential to identify conditions that are potentially dangerous for kidney and urinary tract well-being, for which LUTS can be the first manifestation. Starting from a series of clinical scenarios, we will underline the diagnostic clues behind LUTS in children and we will summarize clinical and surgical approaches for the proper management of these conditions.

We investigated prevalence of and factors associated with acute kidney injury (AKI) in a group of patients hospitalized with viral bronchiolitis. We retrospectively enrolled 139 children (mean age = 3.2 ± 2.1 months; males = 58.9%) hospitalized for viral bronchiolitis in a non-pediatric intensive care unit (PICU) setting. The Kidney Disease/Improving Global Outcomes creatinine criterion was used to diagnose AKI. We estimated basal serum creatinine by back-calculating it by Hoste (age) equation assuming that basal eGFR were the median age-based eGFR normative values. Univariate and multivariate logistic regression models were used to explore associations with AKI. Out of 139 patients, AKI was found in 15 (10.8%). AKI was found in 13 out of 74 (17.6%) patients with and in 2 out of 65 (3.1%) without respiratory syncytial virus (RSV) infection (p = 0.006). No patient required renal replacement therapies, while 1 out of 15 (6.7%) developed AKI stage 3, 1 (6.7%) developed AKI stage 2, and 13 (86.6%) developed AKI stage 1. Among the 15 patients with AKI, 13 (86.6%) reached the maximum AKI stage at admission, 1 (6.7%) at 48 h, and 1 (6.7%) at 96 h. At multivariate analysis, birth weight p = 0.002), preterm birth (OR = 20.3; 95% CI = 3.1–129.5; p = 0.002), RSV infection (OR = 27.0; 95% CI = 2.6–279.9; p = 0.006), and hematocrit levels > 2 standard deviation score (SDS) (OR = 22.4; 95% CI = 2.8–183.6; p = 0.001) were significantly associated with AKI.Conclusion: About 11% of patients hospitalized with viral bronchiolitis in a non-PICU setting develop an AKI (frequently mild in degree). Preterm birth, birth weight 2SDS, and RSV infection are significantly associated with AKI in the setting of viral bronchiolitis. What is Known:• Viral bronchiolitis affects children in the first months of life and in 7.5% of cases it can be complicated by acute kidney injury (AKI).• No studies investigated associations with AKI in infants hospitalized for viral bronchiolitis. What is New:• About 11% of patients hospitalized with viral bronchiolitis can develop an AKI (frequently mild in degree).• Preterm birth, birth weight 2 standard deviation score, and respiratory syncytial virus infection are associated with AKI development in infants with viral bronchiolitis.

Background: Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). Methods: A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. Results: At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. Conclusions: Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted.

BackgroundThyroid hormones (TH) play multiple effects on glucose metabolism. Some recent studies carried out in adult patients suggested an association between altered sensitivity to TH and type 2 diabetes, obesity, and metabolic syndrome. No studies are currently available on the presence of altered sensitivity to the action of TH in youths with prediabetes.ObjectiveTo evaluate the relationship between sensitivity to TH and impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or glycosylated hemoglobin (HbA1c) ≥ 5.7% in youths with overweight/obesity (OW/OB).Materials and methodsThis cross-sectional study included 805 Caucasian youths with OW or OB (aged 6-18 years) recruited at seven Italian centers for the care of OW/OB. Individuals with TH out of the normal range of TH in each center were excluded. The fT3/fT4 ratio was evaluated to assess peripheral sensitivity, while TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI) and Parametric TFQI were calculated to assess central sensitivity.ResultsYouths with IGT (n =72) showed higher levels of TSH (3.08 ± 0.98 vs 2.68 ± 0.98 mIU/L, P =0.001), TSHI (3.06 ± 0.51 vs 2.85 ± 0.53, P =0.001), TT4RI (46.00 ± 17.87 vs 38.65 ± 16.27, P ConclusionIGT was associated with a reduced central sensitivity to TH in youths with OW/OB. Our finding suggests that IGT phenotype, known to be associated with an altered cardiometabolic risk profile, might also be associated with an impaired TH homeostasis in youths with OW/OB.

Combination therapy (CT) (desmopressin plus oxybutynin) has been considered for the treatment of monosymptomatic nocturnal enuresis (MNE). We designed our study with the aim to evaluate the response rate to CT compared with desmopressin alone (primary outcome) and to identify factors associated with the response to CT (secondary outcome). We prospectively enrolled children with MNE with absent/partial response after 3 months of evening treatment with 240 mcg of desmopressin. We defined the response rate to CT compared with desmopressin alone according to the standardization of terminology document of the International Children's Continence Society: no-response, < 50% reduction; partial response, 50 to 99% reduction; and complete response, 100% reduction of wet nights. Both partial response and complete response to CT were clustered for the analyses of this manuscript. The enrolled children treated with 240 mcg/evening of desmopressin had also an additional evening administration of 0.3 mg/kg oxybutynin. A follow-up was scheduled at 3 and 6 months after the beginning of CT. At 3 months, oxybutynin dose was augmented to 0.5 mg/kg in case of absent/partial response to CT. Nocturnal diuresis was measured in 5 wet nights prior the beginning of therapy with desmopressin. Nocturnal polyuria (NP) was defined as nocturnal urine production > 130% of the expected bladder capacity. All patients with constipation were treated with macrogol. We enrolled 81 children (35.8% females) with a mean age of 8.4 +/- 2.3 years. Seventy-eight patients completed the follow-up. After the CT, 59/78 (75.6%) patients showed an improvement of the response with CT compared with desmopressin alone. At multivariate analysis, both NP in more than 1 night (OR = 8.5; 95% CI, 1.4-51.6; p = 0.02) and absence of constipation (OR = 7.1; 95% CI, 1.6-31.0; p = 0.009) resulted significant after Bonferroni correction.Conclusions: CT determines an improvement of response compared to therapy with desmopressin alone in 75.6% of patients. Significant predictive factors of response to CT were presence of NP and absence of constipation.

Nutcracker syndrome (NCS) is a rare pediatric disease caused by left kidney vein compression. Besides the “Triade’s symptoms”, including hematuria, proteinuria, and flank pain, a wide spectrum of clinical manifestations has been reported. As the significant hemodynamic changes secondary to the dilatation of the left renal vein, serious consequences such as renal vein thrombosis and severe anemia might occur in these children. NCS diagnosis includes a variety of invasive and non-invasive imaging tools, but cutoff values need to be further validated. A conservative treatment represents the most common therapeutic approach for these patients, but operative options are available in selected cases. To complicate matters, a standard diagnostic and treatment algorithm is currently lacking and scientific pediatric evidence in this field is still poor and limited. In this perspective, early recognition of NCS is crucial but challenging for pediatricians. Therefore, a better knowledge of the disease is recommended. Starting from two different clinical presentations of NCS, we aimed to provide a comprehensive overview of the disease in children.

Background: Phenylketonuria (PKU) is a rare congenital disorder caused by decreased metabolism of phenylalanine determining cerebral impairments. If untreated, PKU might lead to intellectual disability, seizures and behavioral disorders. The aim of this study is to provide a characterization of the psychopathological profile of a pediatric population diagnosed with PKU at newborn screening. Methods: an accurate neuropsychological evaluation of 23 patients (aged 8–18 years) with hyperphenylalaninemia (defined as experimental group, EG) and in 23 age-matched healthy controls (defined as control group, CG) was performed using the Child and Adolescent Behavior Inventory (CABI) and Self-Administrated Psychiatric Scales for Children and Adolescents (SAFA) questionnaires. Results: the CABI test showed significant differences for the sub-scales related to “Irritable mood”, “Oppositional-provocative symptoms” and “ADHD” in the EG compared to CG (p = 0.014, p = 0.032, and p = 0.032, respectively). Patients with hyperphenylalaninemia also presented with significant differences both for anxiety disorder scale and depression scale of SAFA test than controls (p = 0.018 and p = 0.009, respectively). Conclusions: children and adolescents with early diagnosis of PKU showed a psychopathological risk profile characterized by an increased risk of experiencing symptoms such as mood deflection, anxiety, attention deficit, oppositional defiant behavior, and obsessive traits than healthy peers. Our findings highlighted the need of the inclusion of a neuropsychiatric evaluation in the management of these patients to improve their overall quality of life.

To evaluate the course of prenatally diagnosed and early-enrolled congenital solitary functioning kidney patients followed until adulthood and to identify risk factors for kidney injury.Among all congenital solitary functioning kidney patients followed (1993-2018), we recalled 56 patients with prenatal diagnosis and congenital solitary functioning kidney confirmation at 1-3 months of life reaching at least 18 years of age. Serum uric acid, heavy smoking (≥25 cigarettes/day) and overweight/obesity were clustered as modifiable risk factors. Kidney injury was defined by estimated glomerular filtration rate90 ml/minute/1.73 mThe mean followup period was 21.1 years (range 18-33 years). Mild kidney injury was found in 15 out of 56 patients (26.8%). The mean age at proteinuria, reduced estimated glomerular filtration rate and hypertension onset was 19.7 years (1.2 SDS), 20.7 years (2.7 SDS), and 22 years (5.6 SDS), respectively. Patients with CAKUT of congenital solitary functioning kidney and with both CAKUT of congenital solitary functioning kidney and modifiable risk factors presented survival free from kidney injury of 0% at 22.2 and 24.2 years of age, respectively. Patients with modifiable risk factors presented 42.4% of survival at 30 years. Patients without CAKUT of congenital solitary functioning kidney nor modifiable risk factors presented 100% of survival at 30 years of age (p=0.002). The presence of CAKUT of congenital solitary functioning kidney was the only significant risk factor (HR 4.9; 95% CI 1.8-14.2; p=0.003).The outcomes of congenital solitary functioning kidney in early adulthood appear better than previously reported. Prompt diagnosis of congenital solitary functioning kidney, healthy lifestyle promotion and monitoring of serum uric acid may improve the prognosis of congenital solitary functioning kidney patients.

Context Acute kidney injury (AKI) and renal tubular damage (RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus (T1DM) onset are available. Objectives To evaluate the AKI and RTD prevalence and their rate and timing of recovery in children with T1DM onset. Design Prospective study. Settings and patients 185 children were followed up after 14 days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60 days later. Main outcome measures AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa Results Prevalence of diabetic ketoacidosis (DKA) and AKI were 51.4% and 43.8%, respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%, respectively; 33.3% reached AKI stage 2, and 66.7% of patients reached AKI stage 1. RTD was evident in 136/185 (73.5%) patients (32.4% showed ATN; 11.4%, P-AKI; 29.7%, ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14 days and the latter within 2months. Conclusions Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients.

Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver, type 2 diabetes, metabolic syndrome, and cardiovascular disease. From a pathogenic point of view, insulin resistance (IR) represents the key factor underlying the spectrum of these obesity consequences. As observed in adults, recent data supported the occurrence of microalbuminuria (MA) as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity. In fact, a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics. Based on the clinical and prognostic relevance of this relationship in daily practice (including an increased risk of chronic kidney disease development overtime), more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity. In this paper, we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity: (1) What is the prevalence of pediatric MA? (2) What is the state of art of MA in children with obesity? and (3) Is there a link between IR and MA in children with obesity?

Pediatric obesity is associated with an increased risk of morbidity during childhood. Alongside the well-known metabolic syndrome, during the last decades scientific research has deeply investigated the risk of sleep breathing disorders. Among them, obstructive sleep apnea (OSA) commonly affects children with obesity. The presence of OSA heightens the risk of metabolic impairment and weight gain. Therefore, it deserves specific treatment. However, polysomnography (PSG) is not always available in clinical settings, and alternative diagnostic tools are needed. This study aimed to investigate the predictivity of the pediatric sleep questionnaire (PSQ) for moderate-to-severe OSA diagnosis. Children and adolescents with obesity and suspected OSA with available full-night cardiorespiratory PSG were retrospectively enrolled. Receiver operating curve analysis was performed to test the ability of PSQ in predicting moderate-to-severe OSA (AHI > 5 episode/h). The final sample included 60 children and adolescents. The PSQ showed a good area under the curve (AUC) of 0.88 (95% CI 0.78–0.98, p < 0.0001). Moreover, a value above or equal to 0.65 showed an 80% sensitivity and 100% specificity for moderate and severe OSA. These findings suggest that PSQ might be used in clinical settings with limited access to PSG for stratifying disease severity and for selecting children with urgent need of sleep study.

Aim: To assess a new formula to improve the screening of isolated impaired glucose tolerance (IGT) in youth with overweight/obesity (OW/OB). Methods and results: A cross-sectional study was performed in 1189 Caucasian youths with OW/OB aged 5-17 years, in whom impaired fasting glucose and high glycosylated hemoglobin were excluded. The sample was divided into training set (TS) (n=883) and validation set (VS) (n=306). Fasting (FG) and post-load plasma glucose, alanine aminotransferase (ALT), lipids and familial history for type 2 diabetes (FD) were available in all individuals. In the TS youths with IGT (n=58, 7.0%) showed higher prevalence of female sex (FS), FD, and higher levels of FG, post-load glucose, ALT and lower levels of HDL-cholesterol vs individuals without IGT. The linear formula was obtained by logistic regression analysis in the TS: 0.05∗ALT + 0.07∗FG + 0.87∗FD + (0.06∗HDL∗ - 1) + 1∗FS. The best cut-off was 5.84. The performance of the formula vs IGT was: sensitivity: 0.74 and specificity: 0.71. Similar results were obtained in the VS. Conclusions: Using metabolic and anamnestic data we obtained a simple formula with a good performance for screening isolated IGT. This formula may support pediatricians to identify youths with OW/OB in whom the OGTT may be useful for detecting IGT.

The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has gained considerable scientific interest in adults over the past few years. However, this association has recently emerged in children. Several published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age, with a potential influence of the major NAFLD risk polymorphisms, resulting in an increased risk of both cardiovascular and metabolic diseases. In view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD, we focused on the link between these diseases in childhood.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in pediatric obesity. Our study aims to identify a predictive anthropometrical measure for NAFLD in obese children. METHODS We retrospectively enrolled children and adolescents with obesity. Physical, biochemical, and ultrasound assessments were available. ROC curve tests were performed to identify the best predictor of NAFLD among waist-to-height ratio (WHR), BMI z-score, and triponderal mass index (TMI, an anthropometric index recently associated with increased adiposity in children). Subsequently, a cut-off value was identified. RESULTS In total, 1900 children and adolescents (1011 with NAFLD) were included. WHR (AUC 0.62, 95% CI 0.59-0.64) was the best predictor of NAFLD compared to BMI z-score (AUC 0.58, 95% CI 0.55-0.60) and TMI (AUC 0.58, 95% CI 0.55-0.61). WHR ≥ 0.53 in boys and 0.63 in girls displayed the best sensitivity and specificity for NAFLD presence. In addition, children with high WHR showed a significantly higher risk of NAFLD (boys: OR 2.43, 95% CI 1.61-3.68, p

Background and aim: To compare cardiometabolic risk profile and preclinical signs of target organ damage in youth with normal and elevated blood pressure (BP), according to the American Academy of Pediatrics (AAP) guidelines. Methods and results: This cross-sectional multicenter study included 2739 youth (5-17 year-old; 170 normal-weight, 610 overweight and 1959 with obesity) defined non hypertensive by the AAP guidelines. Anthropometric, biochemical and liver ultrasound data were available in the whole population; carotid artery ultrasound and echocardiographic assessments were available respectively in 427 and 264 youth. Elevated BP was defined as BP >= 90th to = 120/80 to

Rationale & Objective: The objective of this study is to evaluate the effect of body mass index (BMI) on estimated glomerular filtration rate (eGFR) levels in children with congenital solitary kidney (CSK). Moreover, we evaluated if other factors could influence this relationship. Study Design: Multicenter cross-sectional study. Setting & Participants: University hospital pediatrics departments. Subjects: Two hundred eighty-one patients with CSK. Predictors: Weight, height, BMI-SDS (standard deviation score), duration of overweight/obesity, pubertal stage, systolic (SBP) and diastolic (DBP) blood pressure, eGFR, and renal ultrasound were obtained at the last follow-up visit. The population was classified on the basis of nutritional status and divided in tertiles for duration of overweight/obesity. We compared eGFR levels among these categories. A simple regression was used to correlate eGFR with BMI-SDS. To evaluate if other factors could influence the relationship between eGFR and BMI-SDS, a general linear model was performed, including gender, birth weight

At type 1 diabetes mellitus (T1DM) onset, acute kidney injury (AKI) is very common. To diagnose AKI, the availability of a baseline serum creatinine (bSCr) is pivotal. However, in most hospitalized children the bSCr is unknown. We aimed to test whether the bSCr estimated on the basis of height (ebSCr) could be a reliable surrogate for AKI diagnosis compared with the measured bSCr (mbSCr). As the mbSCr, we considered the creatinine measured 14 days after T1DM onset while ebSCr (mg/dL) = (k × height [cm])/120 mL/min/1.73 m2, where k = 0.55 for children and adolescent girls and k = 0.7 for adolescent boys. AKI was defined as serum creatinine values >1.5 times the baseline creatinine. Kappa statistics and the percentage of agreement in AKI classification by ebSCr–AKI versus mbSCr–AKI definition methods were calculated. Bland–Altman plots were used to show the agreement between the creatinine ratio (highest/baseline creatinine; HC/BC) calculated with mbSCr and ebSCr. The number of 163 patients with T1DM onset were included. On the basis of mbSCr, 66/163 (40.5%) presented AKI while, on the basis of ebSCr, 50/163 (30.7%) accomplished AKI definition. ebSCr showed good correlation with mbSCr using both the Spearman test (rho = 0.67; p < 0.001) and regression analysis (r = 0.68; p < 0.001). Moreover, at the Bland–Altman plots, the bias of the highest/baseline creatinine ratio calculated on the basis of the mbSCr compared to ebSCr was minimal (bias = −0.08 mg/dL; 95% limits of agreement = −0.23/0.39). AKI determined using ebSCr showed 90% agreement with AKI determined using mbSCr (kappa = 0.66; p < 0.001). Finally, we compared the area under a receiver–operating characteristic curve (AUROC) of HC/BC ratio calculated on the basis of ebSCr with AUROC of the gold standard HC/BC ratio calculated on the basis of mbSCr. As expected, the gold standard had an AUROC = 1.00 with a 95% confidence interval (CI) between 0.98 and 1.00, p < 0.001. The HC/BC ratio calculated on the basis of ebSCr also had significant AUROC (AUROC = 0.94; 95% CI: 0.90–0.97; p < 0.001). The comparison of the two ROC curves showed a p < 0.001. In conclusion, when mbSCr is unknown in patients with T1DM onset, the ebSCr calculated on the basis of height could be an alternative to orientate clinicians toward AKI diagnosis.

Diabetic nephropathy (DN) represents the most common microvascular complication in patients with diabetes. This progressive kidney disease has been recognized as the major cause of end-stage renal disease with higher morbidity and mortality. However, its tangled pathophysiology is still not fully known. Due to the serious health burden of DN, novel potential biomarkers have been proposed to improve early identification of the disease. In this complex landscape, several lines of evidence supported a critical role of microRNAs (miRNAs) in regulating posttranscriptional levels of protein-coding genes involved in DN pathophysiology. Indeed, intriguing data showed that deregulation of certain miRNAs (e.g., miRNAs 21, -25, -92, -210, -126, -216, and -377) were pathogenically linked to the onset and the progression of DN, suggesting not only a role as early biomarkers but also as potential therapeutic targets. To date, these regulatory biomolecules represent the most promising diagnostic and therapeutic options for DN in adult patients, while similar pediatric evidence is still limited. More, findings from these elegant studies, although promising, need to be deeper investigated in larger validation studies. In an attempt to provide a comprehensive pediatric overview in the field, we aimed to summarize the most recent evidence on the emerging role of miRNAs in pediatric DN pathophysiology.

Background: We hypothesized that children with congenital solitary functioning kidney (CSFK) present forms of congenital urinary tract anomalies (CUTA) with higher chance of spontaneous resolution compared with patients with two kidneys. Methods: We retrospectively selected 75 consecutive children with CUTA of the CSFK and 75 matched patients with unilateral CUTA but without CSFK (controls) with prenatal suspicion of unilateral CUTA and early evaluation. We compared the spontaneous CUTA resolution and the prevalence of kidney injury between groups at last follow-up. Patients and controls were clustered under the categories of “severe” and “non-severe” CUTA. Results: The mean age at first and last follow-up was 0.17 ± 0.07 and 8.5 ± 5.2 years. Compared with controls, patients with CSFK had lower prevalence of severe CUTA at first evaluation; lower prevalence of febrile urinary tract infections, need of surgical correction, and higher rate of spontaneous CUTA resolution during follow-up; and a similar prevalence of mild kidney injury at last follow-up. CSFK compared with controls presented higher cumulative proportion of spontaneous resolution from severe CUTA (100 vs 41.8%; p < 0.001) and from the single CUTA sub-categories (severe vesicoureteral reflux, non-obstructive hydronephrosis, and megaureter). Conclusions: CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA compared with controls. Impact: One-third of patients with congenital solitary functioning kidney (CSFK) present congenital urinary tract anomalies (CUTA) and manifest poorer outcomes compared with CSFK without CUTA.CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA in spite of similar prevalence of kidney injury compared with controls.This adds evidence about disturbed nephrogenesis in CSFK patients and emboldens conservative management of many of their non-obstructive CUTA.

We aimed to evaluate the prognostic value of renal length (RL) > 2 standard deviation scores (SDS) measured by renal ultrasound (RUS), across infancy, childhood and adolescence, in identifying which patients with congenital solitary functioning kidney (CSFK) are at lower risk of developing kidney injury (KI). We also estimated the cost saving of integrating the current follow-up protocols with an early RUS algorithm (ERUSA). Fifty-six CSFK adult patients who were 1–3 months old at first observation of undergoing RUS were enrolled. KI was defined by hypertension and/or proteinuria and/or declined renal function. ERUSA was assessed by early (at 1–3 months of life) RUS and was retrospectively tested in our patients. ERUSA establishes that patients with RL > 2SDS at early RUS do not undergo further follow-ups. The others undergo another RUS at 1 year of age along with follow-ups according with current protocols, with the exception of RUS which could be no longer performed. Direct and indirect costs were calculated for each analysed protocol and the cost saving of applying ERUSA was calculated. None of the patients with early RL > 2SDS presented KI in adulthood. A RL > 2SDS was predictive of absence of KI only at 1–3 months (OR = infinity) and 1 year of age (OR = 0.13; 95%CI: 0.03–0.66; p = 0.01). ERUSA provided a total cost-sparing ranging from 38.6% to 55.3% among the analysed follow-up protocols. With ERUSA, no patients developing KI in adulthood were missed. In conclusion, only a RL > 2SDS at 1–3 months and 1 year of age predicted good prognosis in young adulthood. ERUSA can guide a cost-sparing follow-up strategy in CSFK patients while maintaining important long-term information.

Aims To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Materials and Methods Cross-sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5-17 years). Metabolic syndrome was defined by >= 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high-density lipoproteins; (4) fasting glucose >= 100 mg/dl; (5) blood pressure >= 95(th) percentile in children, and >= 130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value >= 75(th) percentile adjusted for sex. Fatty liver disease was determined by echography. Results The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06-1.68) for MetS (p = 0.02), 3.19 (2.51-4.05) for HUA (p < 0.0001) and 3.72 (2.65-5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. Conclusions HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study.

As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the "multiple hits" theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).

Renal diseases in childhood form a spectrum of different conditions with potential long-term consequences. Given that, a great effort has been made by researchers to identify candidate biomarkers that are able to influence diagnosis and prognosis, in particular by using omics techniques (e.g., metabolomics, lipidomics, genomics, and transcriptomics). Over the past decades, metabolomics has added a promising number of ‘new’ biomarkers to the ‘old’ group through better physiopathological knowledge, paving the way for insightful perspectives on the management of different renal diseases. We aimed to summarize the most recent omics evidence in the main renal pediatric diseases (including acute renal injury, kidney transplantation, chronic kidney disease, renal dysplasia, vesicoureteral reflux, and lithiasis) in this narrative review.

Obstructive sleep apnea syndrome (OSAS) in childhood is a complex disease primarily due both to adenotonsillar hypertrophy and pediatric obesity. Notably, inflammation has been recognized as one of the most important shared pathogenic factor between obesity and OSAS resulting in an increased cardiometabolic risk for these patients. To date, evidence is still limited in non-obese population with OSAS. We aimed to evaluate the cardiometabolic risk profile of a pediatric population of non-obese subjects affected by OSAS. A total of 128 school-aged children (mean age 9.70 ± 3.43) diagnosed with OSAS and 213 non-OSAS children (mean age 9.52 ± 3.35) as control group were enrolled. All subjects underwent a complete clinical and biochemical assessment (including white blood cell count (WBC), platelet count (PLT), mean platelet volume (MPV), % of neutrophils (NEU%), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), uric acid, fasting insulin, iron, ferritin, and transferrin levels). A significant association between inflammation markers (including WBC, PLT, MPV, NEU%, ferritin, CPR, and ESR) and OSAS was found (all p < 0.001). Children with OSAS also showed increased transaminase, glucose, uric acid, and insulin levels (all p < 0.001) compared to healthy controls. Conclusion: Taken together, these findings suggested a worse cardiometabolic profile in non-obese children with OSAS. Given the pivotal pathogenic role of inflammation both for hypoxiemia and metabolic derangements, therapeutic strategies for OSAS might also counteract the increased cardiometabolic risk of these patients, by improving their long-term quality of life.What is Known:• Pediatric OSAS has shown a close relationship with obesity and its cardiometabolic comorbidities.• Inflammation represents the hallmark of both obesity and OSAS.What is New:• Non obese children with OSAS presented with a worse cardiometabolic risk profile.• OSAS treatment might serve as an effective approach also for the increased cardiometabolic risk of these children.

Gastrointestinal (GI) involvement has been reported in approximately 50% of patients with coronavirus disease 2019 (COVID-19), which is due to the pathogenic role of inflammation and the intestinal function of the angiotensin-converting enzyme 2 and its receptor. Accumulating adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease, however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly known. During the last decades, the crosstalk between gut and lung has been largely recognized resulting in the concept of "gut-lung axis" as a central player in modulating the development of several diseases. Both organs are involved in the common mucosal immune system (including bronchus-associated and gut-associated lymphoid tissues) and their homeostasis is crucial for human health. In this framework, it has been found that the role of GI dysbiosis is affecting the homeostasis of the gut-liver axis. Of note, a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects, but it remains to be clarified. Based on the increased risk of inflammatory diseases in children with COVID-19, the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this population. We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.

The definition of metabolic syndrome (MetS) in childhood is controversial. Recently, a modified version of the International Diabetes Federation (IDF) definition was proposed using reference data from an international population for high waist circumference (WC) and blood pressure (BP), while the fixed cutoffs for lipids and glucose were not changed. We analyzed MetS prevalence using this modified definition (MetS-IDFm) and its association with non-alcoholic fatty liver disease (NAFLD) in 1057 youths (age 6–17 years) with overweight/obesity (OW/OB). A comparison with another modified definition of MetS according to the Adult Treatment Panel III (MetS-ATPIIIm) was performed. The prevalence of MetS-IDFm was 27.8% and 28.9% by MetS-ATPIIIm. The Odds (95% Confidence Intervals) of NAFLD was 2.70 (1.30–5.60) (p = 0.008) for high WC, 1.68 (1.25–2.26)(p = 0.001) for MetS, 1.54 (1.12–2.11)(p = 0.007) for low HDL-Cholesterol, 1.49 (1.04–2.13)(p = 0.032) for high triglycerides and 1.37 (1.03–1.82)(p = 0.033) for high BP. No substantial difference was found in the prevalence of MetS-IDFm and frequency of NAFLD compared to Mets-ATPIIIm definition. Our data demonstrate that one third of youths with OW/OB have MetS, whichever was the criterion. Neither definition was superior to some of their components in identifying youths with OW/OB at risk for NAFLD.

We hypothesized that the heart rate (HR) variation in an acute setting compared with HR in wellbeing status could be a good marker of both dehydration and acute kidney injury (AKI). Since HR in wellbeing status is unknown in most cases, we assumed as reliable surrogate the 50th percentile of HR according to age and gender. We evaluated if the estimated percentage of heart rate variation in acute setting compared with 50th percentile of HR (EHRV) could be marker of dehydration and AKI in children. Two independent cohorts, one prospective comprehending 185 children at type 1 diabetes mellitus onset (derivation) and one retrospective comprehending 151 children with acute gastroenteritis and pneumonia (validation), were used to develop and externally validate EHRV as predictor of the ≥ 5% dehydration and/or AKI composite outcome. Febrile patients were excluded. EHRV was calculated as ((HR at admission–50th percentile of HR)/HR at admission) × 100. The prevalences of ≥ 5% dehydration and AKI were 61.1% and 43.8% in the derivation and 34.4% and 24.5% in the validation cohort. For the ≥ 5% dehydration and/or AKI composite outcome, the area under receiver-operating characteristic curve of the EHRV in the derivation cohort was 0.69 (95%CI, 0.62–0.77; p 24.5%. In the validation cohort, EHRV > 24.5% showed specificity = 100% (95%CI, 96.2–100.0), positive predictive value = 100%, and negative predictive value = 67.1% (95%CI, 64.7–69.5). The positive likelihood ratio was infinity, and odds ratio was not calculable because all the patients with EHRV > 24.5% showed ≥ 5% dehydration and/or AKI. Conclusions: EHRV appears a rather reliable marker of dehydration and AKI. Further validations could allow implementing EHRV in the clinical practice. What is Known:• Increased heart rate (HR) is an easily and quickly detectable sign of dehydration in childhood, but its cut-off to suspect dehydration or acute kidney injury (AKI) is not defined. What is New:• We found that a percentage of estimated HR variation in acute setting in comparison with 50th percentile of HR (EHRV)>24.5% predicted ≥5% dehydration and/or AKI in non-febrile patients.• We provide a one-page tool to suspect ≥5% dehydration and/or AKI on the basis of the HR. If furtherly validated, this tool could be implemented in the daily clinical practice.

Non-alcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in childhood. To date, the "multiple-hit" hypothesis is largely recognized as an explanation of NAFLD pathogenesis and progression. Obesity and features of the metabolic syndrome have been closely linked to NAFLD development. Due to the increased prevalence of obesity worldwide, NAFLD has reached epidemic proportions over time. Given its unfavorable cardiometabolic burden (such as cardiovascular and metabolic consequences), it represents a worrying phenomenon needing a more comprehensive and successful management. Laboratory tests and classical imaging techniques play a pivotal role in NAFLD diagnosis, but novel noninvasive alternative methods to diagnose and monitor NAFLD have been investigated. Currently, lifestyle modifications remain the mainstay treatment, although its efficacy is poor because of the lack of compliance. Pediatric research is focusing on multiple alternative treatments targeting the main pathogenic factors such as insulin-resistance, dyslipidemia, gut-liver axis and microbiota, oxidative stress, and proinflammatory pathways. Results from these studies are promising but larger validation is needed. Innovative therapeutic approaches might add an important piece in the complex knowledge of pediatric NAFLD. We aimed to summarize recent insights into NAFLD diagnosis and treatment in children, with a focus on possible future perspectives in pediatric research.

BACKGROUND In paediatric patients with complicated nephrotic syndrome (NS), rituximab (RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G (IgG) levels. AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels. METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation (SD)]. RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients (55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two "starting doses" experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose. CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.

Three new equations for calculating the estimated basal serum creatinine (ebSCr) in hospitalized children have been developed: the simplified acute kidney injury (AKI) baseline creatinine (ABC) equation which considered only age in the formula; the equation including age and minimum creatinine (Crmin) within the initial 72 h from hospitalization (ABC-cr); and the equation including Crmin and height, weight, and age as squared values (ABC-advanced). We aimed to test the diagnostic performance of the ABC, ABC-cr and ABC-advanced equations in diagnosing AKI in 163 prospectively enrolled children with type 1 diabetes mellitus (T1DM) onset. We considered measured basal serum creatinine (mbSCr), the creatinine measured 14 days after T1DM onset. AKI was defined by the highest/basal serum creatine (HC/BC) ratio > 1.5. On the basis of the mbSCr, the AKI was diagnosed in 66/163 (40.5%) patients. This prevalence was lower than the prevalence of AKI diagnosed on the basis of ABC ebSCr (122/163 patients; 74.8%) (p < 0.001) and similar to the prevalence of AKI diagnosed on the basis of ABC-cr ebSCr (72/163 patients; 44.2%) (p = 0.5) and to the prevalence of AKI diagnosed on the basis of ABC-advanced ebSCr (69/163; 42.3%) (p = 0.73). AKI determined using ABC ebSCr, ABC-cr ebSCr and ABC-advanced ebSCr showed, respectively, 63.5% (kappa = 0.35; p < 0.001), 87.7% (kappa = 0.75; p < 0.001), and 87.1% (kappa = 0.74; p < 0.001) agreement with AKI determined using mbSCr. Using the HC/BC ratio calculated on the basis of mbSCr as gold standard, for Bland–Altman plots the HC/BC ratio calculated on the basis of ABC formula presented higher bias and wider limits of agreement compared with the HC/BC ratio calculated on the basis of ABC-cr and ABC-advanced formulas. In the receiver–operating characteristics (ROC) curve analysis the HC/BC ratio calculated on the basis of ABC ebSCr presented lower area under the ROC curve (AUROC) (AUROC = 0.89; 95%CI: 0.85–0.95; p < 0.001) compared with HC/BC ratio calculated on the basis of ABC-cr (AUROC = 0.94; 95%CI: 0.91–0.98; p < 0.001) or ABC-advanced ebSCr (AUROC = 0.914; 95%CI: 0.91–0.97; p < 0.001). In both Bland–Altman plots and ROC curve analysis, the ABC-cr and ABC-advanced formulas performed similarly. In conclusion, the ABC-cr and ABC-advanced formulas present very good diagnostic performance toward AKI identification in a population of children with T1DM onset.

Introduction: Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown. Areas covered: We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood. Expert opinion: Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients.

Background: Recently, the new definition of Metabolic (dysfunction) associated fatty liver disease (MAFLD) has gained remarkable scientific interest. We aimed to evaluate the effectiveness of MAFLD definition in selecting obese children at higher cardiovascular risk. Methods: A total of 954 obese children and adolescents was retrospectively enrolled. Clinical, biochemical, and metabolic evaluations were performed. Hepatic steatosis was assessed by liver ultrasound. According to the metabolic status, the population was divided in three groups. Group 1 included obese patients without both non-alcoholic fatty liver disease (NAFLD) and metabolic dysregulation; group 2 included patients with obesity and NAFLD (then encompassing one MAFLD criterion); group 3 included patients with obesity, NAFLD and evidence of metabolic dysregulation (then encompassing more than 1 MAFLD criteria). Results: Patients of Group 3 showed a worse cardiometabolic profile, as also proven by the higher percentage of prediabetes (defined as the presence of impaired fasting glucose or impaired glucose tolerance) compared to other groups (p = 0.001). Conclusions: MAFLD criteria in obese children seem to be less accurate in identifying patients having an intrinsic higher cardiometabolic risk. This suggests the need for a more accurate definition in the context of pediatric obesity.

The rapid global spread of coronavirus disease 2019 (COVID-19) infection has become a major health issue with higher morbidity and mortality rates. Besides respiratory symptoms, a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement. In this regard, several data supported an association between COVID-19 infection and liver injury in adults, while in children there is compelling but currently limited evidence. In particular, patients with COVID-19 have shown a higher risk of liver injury (mainly expressed as increased transaminase levels or hepatic steatosis). Conversely, a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver diseases. The dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19, but other different pathogenic mechanisms have also been supposed. Of note, patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection. This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients. Taking into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood, a strict monitoring of this condition is recommended. We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.

Background: Vesicoureteral reflux (VUR) may be associated with renal dysplasia and reduced renal length (RL). The diagnosis of VUR in children with congenital solitary functioning kidney (CSFK) identifies patients at risk of kidney injury but exposes to invasive procedures. Objective: We aimed to test the hypothesis that an RL >2 standard deviation score (SDS) in the first months of life – reflecting renal hyperplasia – could identify CSFK patients with lower probability of presenting VUR. Method: We retrospectively selected 207 CSFK patients with prenatal diagnosis of CSFK and having undergone renal ultrasound (RUS) both at 0–3 and 10–13 months of life, renal scintigraphy, and cystourethrography/cysto­scintigraphy. We compared the cumulative proportion of an RL >2 SDS by Kaplan-Meier analysis and evaluated the odds to present VUR of patients with an RL >2 SDS both at the first and second RUS. Results: Overall, 3.3% of patients with VUR and 22.0% of patients without VUR presented an RL >2 SDS at the first RUS (p = 0.02). At the second RUS, 53.3% of patients with VUR and 52.5% of patients without VUR presented an RL >2 SDS (p = 0.93). Patients without VUR presented higher cumulative proportion of an RL >2 SDS at 3 months of life than those with VUR (p = 0.02). This difference however disappeared at 11 and 13 months of age (p = 0.17 and p = 0.54, respectively). An RL >2 SDS within 3 months of life presented an OR for VUR of 0.12 (95% CI: 0.02–0.92; p = 0.005), while an RL >2 SDS at 12 months of life presented an OR for VUR of 0.96 (95% CI: 0.45–2.1; p = 0.93). Conclusion: Only an RUS made in the first months of life could identify CSFK patients at lower risk of presenting an associated VUR.

Background: Autism Spectrum Disorder (ASD) is characterized by impairments in social interaction and reciprocal communication. ASD affects about 1% of the general population and is associated with substantial disability and economic loss. A variety of approaches to improve the core deficits and lives of people with ASD have been developed, including behavioral, developmental, educational, and medical interventions. The main objective of this study was to evaluate the efficacy of a neuro-psychomotor approach in children affected by ASD. Methods: The sample consisted of 84 children (66 males, mean age 56.9 ± 15.8 months) affected by ASD assessed between September 2020 to March 2021. The trained therapist was asked to complete the ASD behavior inventory (ASDBI) test at baseline (T0) (September 2020) and after six months (T1) (March 2021) to assess the child’s evolution over the observational period. The study was carried out in southern Italy (Campania Region). Results: ASD children showed a significant improvement for AUTISM composite after 6 months of neuro-psychomotor treatment (T1) compared to baseline (65.4 ± 12.2 vs. 75.8 ± 11.5, p < 0.0001). In particular, significant changes were observed for such domains as the problems of excitability (ECCIT), aggression (AGG), behaviors in social relations (RELSOC), expressive (all p < 0.001), sense/perceptual contact modes (SENS) (p = 0.0007), ritualisms/resistance to changes (RIT) (p = 0.0002), pragmatic/social problems (PPSOC) (p = 0.0009), specific fears (FEARS) (p = 0.01), and learning and memory (AMLR) (p = 0.0007). No differences for the domains Semantic/pragmatic problems (PPSEM) and language (LESP) were found. Conclusions: Our preliminary results suggest the usefulness of the neuro-psychomotor treatment in children with ASD. Although promising, these findings need to be tested further to better understand the long-term effects of this specific type of approach.

Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January 2020. Since then, several measures to limit virus transmission have been imposed; among them, home confinement has been the most severe, with drastic changes in the daily routines of the general population. The "stay at home" rule has impaired healthcare service access, and patients with chronic conditions were the most exposed to the negative effects of this limitation. There is strong evidence of the worsening of obesity and diabetes mellitus in children during this period. To overcome these issues, healthcare providers have changed their clinical practice to ensure follow-up visits and medical consultation though the use of telemedicine. Telemedicine, including telephone calls, videocalls, data platforms of shared telemedicine data platforms mitigated the negative effect of pandemic restrictions. Published evidence has documented good metabolic control and weight management outcomes in centers that performed extensive telemedicine services last year during the pandemic. This review discusses studies that investigated the use of telemedicine tools for the management of pediatric obesity and diabetes.

Background: Owing to the increasing rate of pediatric obesity, its complications such as non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) have become prevalent already in childhood. We aimed to assess the relationship between these two diseases in a cohort of children with obesity. Methods: We enrolled 153 children with obesity (mean age 10.5 ± 2.66, mean BMI 30.9 ± 5.1) showing OSA. Subjects underwent a laboratory evaluation, a cardio-respiratory polysomnography (PSG), and a liver ultrasound. Results: All subjects had a clinical diagnosis of OSA based on the AHI &gt, 1/h (mean AHI 8.0 ± 5.9, range 2.21–19.0). Of these, 69 showed hepatic steatosis (62.3% as mild, 20.3% as moderate, and 17.4% as severe degree). A strong association between ALT and apnea/hypopnea index (AHI) was observed (p = 0.0003). This association was not confirmed after adjusting for hepatic steatosis (p = 0.53). By subdividing our population according to the presence/absence of steatosis, this association was found only in the steatosis group (p = 0.009). As the severity of steatosis increased, the significance of its association with AHI compared to the absence of steatosis became progressively stronger (all p &lt, 0.0001). Conclusions: Hepatic steatosis seems to drive the association between OSA and ALT levels, suggesting a potential pathogenic role of OSA in NAFLD.