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Author(s): Pierluigi Marzuillo [sup.1] , Gemma Carreras-Badosa [sup.2] , José-María Martínez-Calcerrada [sup.3] , Stefano Guarino [sup.1] , Pier Luigi Palma [sup.1] , Delfina Petrone [sup.1] , Emanuele Miraglia del Giudice [...], Background We evaluated the diagnostic performance of height-, age- and body surface area (BSA)-based kidney length (KL) percentiles in the identification of at least one small kidney (KL < 3.sup.rd) and in the prediction of reduced estimated glomerular filtration rate (eGFR) and/or elevated blood pressure (BP) in children with and without overweight (OW)/obesity(OB). Methods In this cross-sectional study, 744 apparently healthy children (mean age 8.3 years) were recruited in a primary care setting. Clinical data were collected, and serum creatinine and KL were measured. Height-, age- and BSA-based percentiles of KL were calculated and the association of at least one small kidney per subject with reduced eGFR and/or elevated BP was explored by logistic regression. Results Two hundred fifty-seven out of seven hundred forty-four (34.5%) subjects were OW/OB and 127 (17.1%) had reduced eGFR or elevated BP. In separate analyses in children with OW/OB, the KL percentiles calculated on the basis of BSA were lower compared with height- and age-based KL percentiles. Consequently, the prevalence of a small kidney was significantly higher when evaluating percentiles of KL based on BSA compared with other percentiles. In logistic regression analysis, a small kidney was significantly associated with reduced eGFR and/or elevated BP only when using height-based KL percentiles. The KL percentiles according to BSA for the ideal weight (iBSA) showed similar performance compared with height-based percentiles. No differences in the diagnostic performance of different percentiles were found in children with normal weight. Conclusions BSA-based percentiles underestimate KL in children with OW/OB. In these subjects, the use of height-based or iBSA-based percentiles should be preferred. Graphical abstract

Author(s): Giulio Rivetti [sup.1] , Brenden E. Hursh [sup.2] , Emanuele Miraglia del Giudice [sup.1] , Pierluigi Marzuillo [sup.1] Author Affiliations: (1) grid.9841.4, 0000 0001 2200 8888, Department of Woman, [...], Children with type 1 diabetes mellitus (T1DM) have an increased risk of developing kidney involvement. Part of the risk establishes at the beginning of T1DM. In fact, up to 65% of children during T1DM onset may experience an acute kidney injury (AKI) which predisposes to the development of a later chronic kidney disease (CKD). The other part of the risk establishes during the following course of T1DM and could be related to a poor glycemic control and the subsequent development of diabetic kidney disease. In this review, we discuss the acute and chronic effects of T1DM on the kidneys, and the implications of these events on the long-term prognosis of kidney function.

Summary: Background: The diagnosis of monogenic obesity is burdened by frequent variants of uncertain significance (VUS). We describe our real‐life approach of variant reassessment over time and we assess whether inconclusive variants are decreasing in monogenic obesity. Methods: We tested for monogenic obesity (genes: LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in 101 children/adolescents (11.7 [7.3–13.7] years, 3.6 [3.3–4.0] z‐BMI) in Verona and 183 (11.3 [8.4–12.2] years, 3.2 [2.7–3.9] z‐BMI) in Naples from January 2020 to February 2023. In March–July 2024 we reassessed the baseline variants by updated software interpretation and literature renavigation. Results: We initially found 20 VUS, 4 Likely Pathogenic (LP), 5 Likely Benign (LB) and 1 benign variant in 33 individuals. At follow‐up, 6 VUS were reclassified as benign/LB, one LP as pathogenic and 3 LB as benign. Overall, 10/30 variants (6/18 in Verona, 3/11 in Naples and a variant found in both centres) were reclassified, leading to a less uncertain report for 13 of 33 variant‐carrying patients. Monogenic obesity was diagnosed in 3 probands in Verona and 4 in Naples, carrying variants at MC4R or NTRK2. Conclusion: Our variant reassessment was effective to improve classification certainty for the 39% of patients and suggested that the molecular diagnosis of monogenic obesity is becoming more accurate over time. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico‐ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses. Methods: We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided. Results: Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch‐up growth. The remaining six patients exhibited spontaneous catch‐up growth. Conclusion: FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases. [ABSTRACT FROM AUTHOR]

The role of obesity as a risk factor for chronic kidney disease (CKD) in adulthood has been well established. Over the last years, kidney damage (KD) has emerged as a significant consequence of obesity since childhood. Indeed, a complex interplay of metabolic factors, including insulin resistance (IR), hypertension, oxidative stress, adipose tissue dysfunction, and systemic inflammation, might affect renal hemodynamics, contributing to CKD development over time in at-risk young patients. As the prevalence of pediatric obesity continues to rise globally, understanding the implications for kidney health in terms of early intervention is of paramount importance. Careful monitoring of kidney function within a multidisciplinary approach in children with obesity is crucial for detecting early KD, allowing for timely lifestyle modifications and treatment. In this framework, continued research is essential to further elucidate mechanisms linking obesity and KD and to explore not only effective preventive strategies but also the long-term impact of obesity on kidney health in children with obesity. Given the intimate link of KD with the metabolic milieu in children with obesity, we aimed to provide a comprehensive and insightful overview on KD and its implications in pediatric obesity by reviewing the most recent literature in the field. [ABSTRACT FROM AUTHOR]

Author(s): Pierluigi Marzuillo [sup.1] , Vincenza Pezzella [sup.1] [sup.2] , Stefano Guarino [sup.1] , Anna Di Sessa [sup.1] , Maria Baldascino [sup.1] [sup.2] , Cesare Polito [sup.1] , Emanuele Miraglia [...], Background Acute kidney injury (AKI) enhances the risk of later chronic kidney disease. Significant prevalence of AKI is reported in adults with community acquired pneumonia (CAP). We investigated prevalence of and prognostic factors for AKI in children hospitalized for CAP. Methods We retrospectively collected clinical and biochemical data of 186 children (48.4% male; mean age 2.6±2.4 years) hospitalized for X-ray-confirmed CAP. AKI was defined according to Kidney Disease/Improving Global Outcomes creatinine criteria. We considered as basal serum creatinine the value estimated with Hoste (age) equation assuming basal eGFR were median age-based eGFR normative values for children [less than or equal to] 2 years of age and eGFR= 120 mL/min/1.73m.sup.2 for children > 2 years. Univariate and multivariate logistic regression models were used to explore associations with AKI. Results AKI was found in 38/186 (20.4%) patients. No patient required hemodialysis nor reached AKI stage 3, 5 (2.7%) reached AKI stage 2, and 33 (17.7%) AKI stage 1. Mean length of stay was 6.0±1.7, 6.9±2.3, and 12.2±1.5 days, for patients without AKI, stage 1 AKI, and stage 2 AKI (p < 0.001), respectively. Duration of symptoms before hospitalization (OR 1.2; 95%CI 1.09-1.43; p = 0.001), severe pneumonia (OR 11.9; 95%CI 4.3-33.3; p < 0.001), and serum C-reactive protein levels (OR 1.1; 95%CI 1.04-1.23; p = 0.004) were independent AKI predictors. Conclusions About 1/5 of children hospitalized for CAP present a generally mild AKI with a longer stay for those with more severe AKI. Attention should be paid to kidney health of children with CAP especially in presence of higher duration of symptoms before hospitalization, severe pneumonia and higher serum CRP levels. Graphical Abstract

Author(s): Pierluigi Marzuillo [sup.1] , Maria Baldascino [sup.1] [sup.2] , Stefano Guarino [sup.1] , Silverio Perrotta [sup.1] , Emanuele Miraglia del Giudice [sup.1] , Felice Nunziata [sup.2] Author Affiliations: (1) [...], Background We aimed to evaluate prevalence of acute kidney injury (AKI) and its risk factors in children hospitalized for acute gastroenteritis (AGE) to identify early predictors of AKI. Methods We retrospectively collected clinical and biochemical data of 114 children (57.9% male; mean age 2.9 ± 2.8 years) hospitalized for AGE. AKI was defined according to Kidney Disease/Improving Global Outcomes creatinine criteria. We considered basal serum creatinine as value of creatinine estimated with Hoste (age) equation assuming basal eGFRs were median age-based eGFR normative values for children [less than or equal to] 2 years of age, and eGFR 120 mL/min/1.73m.sup.2 for children > 2 years. Univariate and multivariate logistic regression models were used to explore associations with AKI. We included in multivariate analyses only variables with significant p after Bonferroni correction. Results AKI was found in 28/114 (24.6%) patients. No patients required hemodialysis, 2 (1.8%) reached AKI stage 3, 2 (1.8%) AKI stage 2, and 24 (21.0%) AKI stage 1. Mean length of stay was 3.6 ± 1.2, 5.0 ± 1.8, and 10.5 ± 5.8 days, for patients with no, mild, and severe AKI (p < 0.001), respectively. Duration of symptoms before hospitalization (OR = 2.5; 95% CI = 1.3-5.0; p = 0.006), dehydration > 5% (OR = 43.1; 95% CI = 5.4-344.1; p = < 0.001), and serum bicarbonate levels (OR = 1.6; 95% CI = 1.2-2.1; p = 0.001) were independent predictors of AKI. Conclusions About one quarter of patients hospitalized for AGE may suffer from AKI with a longer stay for patients with more severe AKI. Particular attention, however, should be paid to volemia and kidney health of patients with AGE especially in the presence of increased duration of symptoms before hospitalization, dehydration, and lower serum bicarbonate levels. Graphical abstract

Background/Objectives: The pediatric definition of severe obesity (OB) depends on the body mass index (BMI) references. We evaluated different BMI-derived metrics of the World Health Organization (WHO) system to define which cut-off is associated with the highest cardiometabolic risk (CMR); Methods: In this multicentric study, data were retrieved for 3727 youths (1937 boys; 2225 children, 1502 adolescents). OB was defined as BMI > 97th percentile (BMI97th), severe OB was defined as BMI > 99th percentile (BMI99th), BMI ≥ 120% of the 97th percentile (120% BMI97th), or BMI Z-score > 3 (WHO tables), or BMI ≥ the International Obesity Task Force (IOTF) value crossing a BMI of 35 kg/m2 at the age of 18 (IOTF35). The continuous CMR Z-score (sum of residual standardized for age and sex of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, and HDL-cholesterol x −1) and the cluster of at least two CMR factors (hypertension, high triglycerides, low HDL-cholesterol, and high waist-to-height ratio) were calculated. Results: Continuous CMR Z-score was significantly higher both in children or adolescents with severe OB defined by 120% BMI97th compared to BMI99th (p < 0.0001), while it was lower only in adolescents with severe OB defined by 120% BMI97th compared to BMI Z-score >3 (p < 0.0001). Compared to 120% BMI97th, BMI Z-score > 3 and IOTF35 had higher specificity, but lower sensitivity in identifying children and adolescents with clustered CMR factors. Conclusions: The definition of severe OB based on 120% BMI97th is superior to BMI99th but it is inferior to BMI Z score > 3 as far as the association between severe OB and CMR factors is concerned. Pediatricians should take into consideration the implication of the use of different BMI metrics in those countries that recommend the WHO system. WHO BMI Z-score > 3 and IOTF35 can be used interchangeably to predict cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported, even in specialized centers. Mobile health technologies have been used to overcome these limits with contrasting results. This study aims at evaluating the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Seventy-five patients were randomly assigned to standard care or standard care plus mobile app (2:1) using an online randomizer system. The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: At six months of follow-up, the M-App group showed significantly lower dropout rates compared to standard care (p = 0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86, 95% C.I. 1.39–10.42, p = 0.01). After one year, we observed lower albeit non-statistically significant dropout rates in the M-App compared to the standard care group (p = 0.24). No differences were observed in z-score BMI and percentage of BMI reduction between the two groups. Conclusions: Our findings suggest that the mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) presents significant challenges in pediatric care, often remaining underrecognized. This paper provides an overview of pediatric AKI, highlighting its epidemiology, pathophysiology, diagnosis, predisposing conditions, and treatment. AKI in children stems from diverse causes, including renal tubular damage, vasoconstriction, and inflammation. Diagnosis relies on traditional markers such as serum creatinine and urine output, alongside emerging biomarkers such as Cystatin C, NGAL, KIM-1, IL-18, TIMP-2 and IGFBP7, urinary calprotectin, URBP4, L-FABP, and clusterin. Various pediatric conditions predispose to AKI, including type 1 diabetes, pneumonia, bronchiolitis, appendicitis, gastroenteritis, COVID-19, multisystem inflammatory syndrome, sickle cell disease, and malignancies. Treatment entails supportive care with fluid management and, in severe cases, renal replacement therapy. Timely recognition and management are essential to mitigating adverse outcomes. Enhanced awareness and integration of novel biomarkers could improve pediatric AKI care, warranting further research for better diagnosis and management. [ABSTRACT FROM AUTHOR]

Aim: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. Methods: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. Results: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8–15.2; p = 9.4e‐09) and neutrophils levels (OR = 1.13; 95%CI: 1.08–1.2; p = 6.8e‐07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7–6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. Conclusion: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR. [ABSTRACT FROM AUTHOR]