Acute kidney injury in children hospitalised for febrile urinary tract infection.

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.

Clinical and genetic characteristics of Dent's disease type 1 in Europe.

BACKGROUND: Dent's disease type 1 (DD1) is a rare X-linked nephropathy caused by CLCN5 mutations, characterized by proximal tubule dysfunction, including low molecular weight proteinuria (LMWP), hypercalciuria, nephrolithiasis-nephrocalcinosis, progressive chronic kidney disease (CKD) and kidney failure (KF). Current management is symptomatic and does not prevent disease progression. Here we describe the contemporary DD1 picture across Europe to highlight its unmet needs. METHODS: A physician-based anonymous international e-survey supported by several European nephrology networks/societies was conducted. Questions focused on DD1 clinical features, diagnostic procedure and mutation spectra. RESULTS: A total of 207 DD1 male patients were reported; clinical data were available for 163 with confirmed CLCN5 mutations. Proteinuria was the most common manifestation (49.1%). During follow-up, all patients showed LMWP, 66.4% nephrocalcinosis, 44.4% hypercalciuria and 26.4% nephrolithiasis. After 5.5 years, ≈50% of patients presented with renal dysfunction, 20.7% developed CKD stage ≥3 and 11.1% developed KF. At the last visit, hypercalciuria was more frequent in paediatric patients than in adults (73.4% versus 19.0%). Conversely, nephrolithiasis, nephrocalcinosis and renal dysfunction were more prominent in adults. Furthermore, CKD progressed with age. Despite no clear phenotype/genotype correlation, decreased glomerular filtration rate was more frequent in subjects with CLCN5 mutations affecting the pore or CBS domains compared with those with early-stop mutations. CONCLUSIONS: Results from this large DD1 cohort confirm previous findings and provide new insights regarding age and genotype impact on CKD progression. Our data strongly support that DD1 should be considered in male patients with CKD, nephrocalcinosis/hypercalciuria and non-nephrotic proteinuria and provide additional support for new research opportunities.

Parathyroid hormone and phosphate homeostasis in patients with Bartter and Gitelman syndrome: an international cross-sectional study.

BACKGROUND: Small cohort studies have reported high parathyroid hormone (PTH) levels in patients with Bartter syndrome and lower serum phosphate levels have anecdotally been reported in patients with Gitelman syndrome. In this cross-sectional study, we assessed PTH and phosphate homeostasis in a large cohort of patients with salt-losing tubulopathies. METHODS: Clinical and laboratory data of 589 patients with Bartter and Gitelman syndrome were provided by members of the European Rare Kidney Diseases Reference Network (ERKNet) and the European Society for Paediatric Nephrology (ESPN). RESULTS: A total of 285 patients with Bartter syndrome and 304 patients with Gitelman syndrome were included for analysis. Patients with Bartter syndrome type I and II had the highest median PTH level (7.5 pmol/L) and 56% had hyperparathyroidism (PTH >7.0 pmol/L). Serum calcium was slightly lower in Bartter syndrome type I and II patients with hyperparathyroidism (2.42 versus 2.49 mmol/L; P = .038) compared to those with normal PTH levels and correlated inversely with PTH (rs -0.253; P = .009). Serum phosphate and urinary phosphate excretion did not correlate with PTH. Overall, 22% of patients had low serum phosphate levels (phosphate-standard deviation score < -2), with the highest prevalence in patients with Bartter syndrome type III (32%). Serum phosphate correlated with tubular maximum reabsorption of phosphate/glomerular filtration rate (TmP/GFR) (rs 0.699; P < .001), suggesting renal phosphate wasting. CONCLUSIONS: Hyperparathyroidism is frequent in patients with Bartter syndrome type I and II. Low serum phosphate is observed in a significant number of patients with Bartter and Gitelman syndrome and appears associated with renal phosphate wasting.

Management of the congenital solitary kidney: consensus recommendations of the Italian Society of Pediatric Nephrology.

BACKGROUND: In recent years, several studies have been published on the prognosis of children with congenital solitary kidney (CSK), with controversial results, and a worldwide consensus on management and follow-up is lacking. In this consensus statement, the Italian Society of Pediatric Nephrology summarizes the current knowledge on CSK and presents recommendations for its management, including diagnostic approach, nutritional and lifestyle habits, and follow-up. We recommend that any antenatal suspicion/diagnosis of CSK be confirmed by neonatal ultrasound (US), avoiding the routine use of further imaging if no other anomalies of kidney/urinary tract are detected. A CSK without additional abnormalities is expected to undergo compensatory enlargement, which should be assessed by US. We recommend that urinalysis, but not blood tests or genetic analysis, be routinely performed at diagnosis in infants and children showing compensatory enlargement of the CSK. Extrarenal malformations should be searched for, particularly genital tract malformations in females. An excessive protein and salt intake should be avoided, while sport participation should not be restricted. We recommend a lifelong follow-up, which should be tailored on risk stratification, as follows: low risk: CSK with compensatory enlargement, medium risk: CSK without compensatory enlargement and/or additional CAKUT, and high risk: decreased GFR and/or proteinuria, and/or hypertension. We recommend that in children at low-risk periodic US, urinalysis and BP measurement be performed; in those at medium risk, we recommend that serum creatinine also be measured; in high-risk children, the schedule has to be tailored according to kidney function and clinical data.

Born with a solitary kidney: at risk of hypertension.

BACKGROUND: Subjects with a congenital solitary kidney (CSK) are believed to be at risk of hypertension due to their low number of nephrons. However, as CSK is a congenital abnormality of the kidney or urinary tract (CAKUT), subtle dysplastic changes contributing to hypertension cannot be excluded. METHODS: We retrospectively compared office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) between two groups of children with CAKUT, aged 6-18 years: Group A with a CSK and Group B with two kidneys. All had normal renal parenchyma on scintigraphy and normal renal function. OBP and mean systolic and diastolic 24-h, daytime and nighttime ambulatory BP records were analyzed. The distribution of OBP and APBM as continuous values and the prevalence of hypertension (ambulatory/severe ambulatory or masked hypertension) in the two groups were compared. RESULTS: There were 81 patients in Group A and 45 in Group B. Median OBP standard deviation scores were normal in both groups, without significant differences. Median ABPM standard deviation scores, although normal, were significantly higher in Group A and the prevalence of hypertension was higher (ambulatory/severe ambulatory or masked) (33.3 vs. 13.3%, p = 0.019), mainly because of the greater occurrence of masked hypertension. CONCLUSIONS: Our data show that a CSK per se can be associated with an increased risk of hypertension from the pediatric age. Therefore, ABPM, which has proved valuable in the screening of hypertension, is warranted in children with a CSK, even if laboratory and imaging assessment is otherwise normal.

Treatment and long-term outcome in primary distal renal tubular acidosis.

BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate. CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.

Genetics of Congenital Anomalies of the Kidney and Urinary Tract: The Current State of Play.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most frequent form of malformation at birth and represent the cause of 40-50% of pediatric and 7% of adult end-stage renal disease worldwide. The pathogenesis of CAKUT is based on the disturbance of normal nephrogenesis, secondary to environmental and genetic causes. Often CAKUT is the first clinical manifestation of a complex systemic disease, so an early molecular diagnosis can help the physician identify other subtle clinical manifestations, significantly affecting the management and prognosis of patients. The number of sporadic CAKUT cases explained by highly penetrant mutations in a single gene may have been overestimated over the years and a genetic diagnosis is missed in most cases, hence the importance of identifying new genetic approaches which can help unraveling the vast majority of unexplained CAKUT cases. The aim of our review is to clarify the current state of play and the future perspectives of the genetic bases of CAKUT.

Body composition in late preterm infants according to percentile at birth.

BACKGROUND: The data on body composition of late preterm infants, evaluated according to percentile at birth, are scarce. The study aimed to investigate body composition of late preterm infants, according to percentile at birth, and to compare their body composition with that of term newborns. METHODS: A total of 122 (99 appropriate and 23 small for gestational age (SGA)) late preterm infants underwent growth and body composition assessment using an air displacement plethysmography system on the fifth day of life and at term. The reference group was composed of 42 healthy, term, breast-fed infants. RESULTS: At birth, appropriate and SGA late preterm infants had lower fat mass and fat-free mass indexes than term newborns. The fat mass and fat-free mass content increased significantly throughout the study, irrespective of percentile at birth. At term, fat mass index, but not fat-free mass index, was higher in both appropriate and SGA late preterm infants than in term newborns. CONCLUSION: Late preterm infants, irrespective of their percentile at birth, show postnatal growth characterized by predominant fat mass accretion. The potential long-term health clinical implications of these findings need to be further elucidated.

Is nutritional support needed in late preterm infants?

BACKGROUND: Late preterm birth accounts for 70 % of all preterm births. While the impact of feeding problems in very preterm infants has been widely investigated, data on late preterm infants' feeding issues are scarce. The aim of the present study was to investigate the need of nutritional support during hospital stay in a cohort of late preterm infants and to identify the factors that most contribute to its occurrence. METHODS: We analyzed the medical records of late preterm infants, born 2011-2013, admitted to a single institution. Neonatal data, the need for nutritional support, defined as the need for parenteral nutrition or intravenous fluids or tube feeding, and the feeding status at discharge were retrieved. The occurrence of respiratory distress syndrome, congenital malformations/chromosomal diseases, cardiac diseases, sepsis, hypoglycemia, poor feeding and the need for surgical intervention were also collected. RESULTS: A total of 1768 late preterm infants were included. Among the 592 infants requiring a nutritional support, 228 developed a respiratory distress syndrome, two developed a sepsis, one presented with a cardiac disease, 24 underwent a surgical intervention, eight had a chromosomal disease/congenital malformation, 80 had hypoglycemia. In addition, 100 infants required nutritional support due to poor feeding and 149 were born small for gestational age. Birth weight ≤2000 g (adjusted OR = 12.2, 95 % CI 7.5-19.9, p < 0.0001), gestational age of 34 weeks (adjusted OR = 4.08, 95 % CI 2.8-5.9, p < 0.0001), being small for gestational age (adjusted OR = 2.17, 95 % CI 2.8-5.9, p=0.001), having a respiratory distress syndrome (adjusted OR = 79.6, 95 % CI 47.2-134.3, p < 0.0001) and the need of surgical intervention (adjusted OR = 49.4, 95 % CI 13.9-174.5, p < 0.0001) were associated with a higher risk of need of nutritional support during hospital stay. CONCLUSIONS: Late preterm infants are at relatively high risk of requiring nutritional support during hospital stay, especially if they have a birth weight ≤2000 g, a gestational age of 34 weeks, are born small for gestational age, develop a respiratory distress syndrome and require a surgical intervention. The present findings add to the knowledge of late preterm infants' feeding issues and may contribute to tailoring nutritional approaches for these infants.

Randomized outcome trial of nutrient-enriched formula and neurodevelopment outcome in preterm infants.

BACKGROUND: Preterm infants are at risk for adverse neurodevelopment. Furthermore, nutrition may play a key role in supporting neurodevelopment. The aim of this study was to evaluate whether a nutrient-enriched formula fed to preterm infants after hospital discharge could improve their neurodevelopment at 24 months (term-corrected age). METHODS: We conducted an observer-blinded, single-center, randomized controlled trial in infants admitted to the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Italy between 2009 and 2011. Inclusion criteria were gestational age < 32 weeks and/or birth weight < 1500 g, and being fed human milk for < 20% of the total milk intake. Exclusion criteria were congenital malformations or conditions that could interfere with growth or body composition. Included infants were randomized to receive a standard full-term formula or a nutrient-enriched formula up until 6 months of corrected age, using two computer-generated randomization lists; one appropriate for gestational age (AGA) and one for small for gestational age (SGA) infants. We assessed neurodevelopment at 24 months of corrected age using the Griffiths Mental Development Scale and related subscales (locomotor, personal-social, hearing and speech, hand and eye coordination, and performance). RESULTS: Of the 207 randomized infants, 181 completed the study. 52 AGA and 35 SGA infants were fed a nutrient-enriched formula, whereas 56 AGA and 38 SGA infants were fed a standard full-term formula. The general quotient at 24 months of corrected age was not significantly different between infants randomized to receive a nutrient-enriched formula compared with a standard term formula up until 6 months of corrected age (AGA infants: 93.8 ± 12.6 vs. 92.4 ± 10.4, respectively; SGA infants: 96.1 ± 9.9 vs. 98.2 ± 9, respectively). The scores of related subscales were also similar among groups. CONCLUSIONS: This study found that feeding preterm infants a nutrient-enriched formula after discharge does not affect neurodevelopment at 24 months of corrected age, in either AGA or SGA infants, free from major comorbidities. TRIAL REGISTRATION: Current Controlled Trials (http://www.controlled-trials.com/ISRCTN30189842) London, UK.

Lumasiran treatment in pediatric patients with PH1: real-world data within a compassionate use program in Italy.

Background: Primary hyperoxaluria (PH) is a rare, severe genetic disorder, characterized by increased urinary excretion of calcium oxalate, which is responsible for kidney damage and systemic clinical manifestations. Since the year 2020, a new molecule, lumasiran, based on RNA interference (RNAi) technology, has been added to the traditional therapeutic approach. The aim of this analysis was to define the baseline characteristics of a PH1 pediatric population treated with lumasiran in a compassionate-use program setting, and to evaluate the medium-term efficacy of this drug in the routine clinical setting. Methods: A retrospective observational analysis was conducted in nine pediatric patients (male:female 5:4; median age at lumasiran start 1.9 years, range 0-14.1). Data concerning oxalate concentration in plasma and urine, kidney stones events, ultrasound and kidney function were collected during the study period (follow-up, mean ± standard deviation: 15.3 ± 5 months). Results: In this analysis, a reduction in the urinary oxalate to creatinine ratio (reduction range within the sixth month of treatment from 25.8% to 69.6%, median 51.2%) as well as plasma oxalate concentration under the limit of supersaturation of oxalate in all the patients. Only one patient presented new stone events; kidney ultrasonographic findings related to nephrocalcinosis remained stable in eight out of nine patients. Glomerular filtration rate remained stable during treatment. No adverse events related to lumasiran were noted. Conclusion: Data from this analysis support the efficacy and safety of lumasiran in a pediatric clinical setting, especially if administrated in early life.

Case Report: effect of lumasiran treatment in a late preterm baby with antenatal diagnosis of primary hyperoxaluria type 1.

Background: Primary hyperoxaluria type 1 (PH1) is a rare disease with autosomal recessive transmission, characterized by increased urinary excretion of oxalate, resulting in chronic kidney disease secondary to recurrent urolithiasis, nephrocalcinosis, and accumulation of oxalate in various organs and tissues (systemic oxalosis). Since 2020, an innovative pharmacological approach, namely, lumasiran, has been added to the therapeutic armamentarium (dialysis and liver-kidney transplantation). The purpose of this paper is to describe the effect of lumasiran initiated at 10 days of life in a newborn with prenatally diagnosed PH1. A female fetus was prenatally diagnosed with hyperoxaluria type 1, based on family history and genetic testing. Her brother had the onset of the disease at 2 months of age and underwent liver and kidney transplantation at 13 months and 8 years of age, respectively. The baby was born late preterm at 36 weeks + 4 days of gestation via spontaneous labor, and lumasiran for compassionate use was started on the tenth day of life. At 20 months of age, the baby showed normal urinary oxalate values and kidney function, while the plasma oxalate level was under the threshold of oversaturation. There were no signs of systemic oxalosis. Conclusions: Early use of lumasiran in young infants, who do not yet show signs of the disease, represents a therapeutic challenge for the pediatric nephrologist. The ability of the drug to act on the hepatocyte of the newborn and the most appropriate dosage to be used in these very young babies have yet to be clarified.

Viral shedding in children infected by pandemic A/H1N1/2009 influenza virus.

BACKGROUND: The aim of this study was to investigate viral shedding in otherwise healthy children with pandemic A/H1N1/2009 influenza in order to define how long children with pandemic A/H1N1/2009 influenza shed the virus, and also plan adequate measures to control the spread of the disease within households. FINDINGS: In 74 otherwise healthy children with pandemic A/H1N1/2009 influenza, nasopharyngeal swabs were taken for virus detection upon hospital admission and every two days until negative. The nasopharyngeal swabs of all of the children were positive for pandemic A/H1N1/2009 influenza virus in the first three days after the onset of infection, and only 21.6% and 13.5% remained positive after respectively 11 and 15 days. No child was positive after more than 15 days. Viral load also decreased over time, and was not associated with patient age or the risk of pneumonia. Those who shed the virus for ≥ 9 days were not at any increased risk of suffering from more severe disease in comparison with those who shed the virus for a shorter time, but their households experienced a significantly higher number of influenza-like illness during the two weeks after the onset of the initial disease (72.3% vs 41.4%; p < 0.05). CONCLUSIONS: Regardless of their age, healthy children can shed pandemic A/H1N1/2009 influenza virus for up to two weeks after illness onset, and the households of the children who shed the virus for ≥ 9 days suffered a higher number of influenza-like illness in the two weeks following the onset of the first disease. This could suggest that when a completely unknown influenza virus is circulating, isolation period of infected children has to be longer than the 7 days recommended for the infections due to seasonal influenza viruses.

Antibody response of healthy children to pandemic A/H1N1/2009 influenza virus.

BACKGROUND: Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). RESULTS: Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥ 40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (p < 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus. CONCLUSIONS: Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.

Quality of growth in exclusively breast-fed infants in the first six months of life: an Italian study.

Nutrition in early life, growth, and subsequent health over a lifetime are significantly interrelated. The aim of this study was to assess body composition changes in exclusively breast-fed infants from birth up to 6 mo of age. An observational, prospective, cohort study was conducted. Fifty-nine full-term, healthy, exclusively breast-fed infants underwent assessment of growth and body composition, using air-displacement plethysmograph (i.e. PEA POD) by Life Measurement, Inc. (Concord, CA). Body composition was assessed at birth, 2 wk, and 1, 2, 3, 4, 5, and 6 mo of age. Mean birth weight (g) and gestational age (wk) of the infants were 3170 ± 420 and 39.21 ± 1.29, respectively. Percentage of fat mass increased significantly over the first 4 mo (p < 0.001), both in boys and girls, with no differences detected between boys and girls at any time point. This article provides preliminary in-depth data on whole-body composition, in exclusively breast-fed infants during the first months of life. Further studies assessing larger sample sizes are desirable to develop reference body composition data.

Blood urea nitrogen concentrations in low-birth-weight preterm infants during parenteral and enteral nutrition.

OBJECTIVES: Early amino acid administration has been recommended in preterm neonates to avoid protein catabolism. In the present work, blood urea nitrogen (BUN) was used to evaluate the quantity of protein intake in preterm infants. The aim of the study was to investigate the relation between protein intake and BUN during the entire duration of parenteral and enteral nutrition. PATIENTS AND METHODS: We conducted a prospective, longitudinal, observational study. BUN was assessed in 92 preterm newborns on days 2, 5, and 15 of parenteral nutrition, on the day when infants consumed 160 mL/kg of milk, and at 36 weeks of postmenstrual infants' age. Protein intakes were calculated from the 24-hour period preceding the time the BUN specimens were collected. The effects of gestational age and protein intakes on BUN concentrations during parenteral nutrition were ascertained by multiple regression analyses. The relation between BUN and protein intakes during enteral feeding was evaluated by a simple correlation analysis. RESULTS: Using linear regression analyses, gestational age showed a significant negative correlation with BUN concentrations during parenteral nutrition, whereas protein intakes at 2, 5, and 15 days did not correlate with BUN. A moderately positive correlation between BUN and protein intake was found when the infants consumed 160 mL/kg of milk and at 36 weeks of postmenstrual age (r = 0.5, P = 0.001 and r = 0.49, P = 0.012, respectively). CONCLUSIONS: In the early postnatal period, high BUN could be the effect of many factors other than amino acid intolerance. In contrast, BUN may represent a useful index in monitoring the adequacy of protein intake during enteral nutrition.

Pediatric nephrolithiasis: a systematic approach from diagnosis to treatment.

Nephrolithiasis is a rare disease in children. For many years children with kidney stones have been managed like "small adults", but there are significant differences between the pediatric and the adult age in clinical presentation, etiology and treatment. Management of this condition in children has some peculiarities with respect to the adult, as it is often the sign of an underlying metabolic abnormality. Some of these metabolic alterations can lead to serious consequences, such as chronic renal failure, if not adequately diagnosed and treated. Moreover, stones in children with a metabolic abnormality can recur throughout their life, with the need for repeated surgical procedures over the years. So a systematic approach to every child with nephrolithiasis is mandatory to diagnose metabolic defects and establish a personalized therapy. Even the surgical approach in the child has changed significantly over the last two decades: open surgery has now been almost completely replaced by minimally invasive surgery due to the miniaturization of endoscopic instruments and technical advancements in optical and lithotripters systems. The goal is to obtain a stone-free status with the lowest number of minimally invasive procedures and with no complications. Many breakthroughs in our understanding of the physiopathology of renal stones and in surgical technology have been made over the last decades, but the best approach to use in a child with nephrolithiasis remains a true challenge for pediatric nephrologists and urologists.

A Case of Hypotonia-Cystinuria Syndrome With Genito-Urinary Malformations and Extrarenal Involvement.

Hypotonia-Cystinuria syndrome (HCS) is a rare disease, caused by a mutation in two contiguous genes (SLC3A1 and PREPL) localized on chromosome 2p21, and it is characterized by both renal involvement with cystine stones and nervous involvement with hypotonia. We here describe a 2 years old child with HCS associated with other clinical features as congenital anomalies of kidney and urinary tract (primary obstructed megaureter, POM), cryptorchidism and cardiac involvement (patent foramen ovale with atrial septum aneurysm). To the best of our knowledge, cryporchidism and POM have never been reported before in patients with HCS. Moreover, a cardiac involvement has been described only in another case of HCS that, interestingly, presents the same genetic abnormalities as our patient. The diagnosis of HCS can be difficult because neurological signs are aspecific and kidney stones are commonly absent during the first months of life. A better understanding of the complete clinical scenario associated with HCS can help clinicians suspect, diagnose and treat HCS earlier with a positive influence on both neurological and renal outcome.

Is Fat Mass Accretion of Late Preterm Infants Associated with Insulin Resistance?

BACKGROUND: Late preterm infants show a major fat mass accretion from birth to term. The contribution of preterm birth to the development of the metabolic syndrome is still under investigation. OBJECTIVES: To evaluate body composition changes in late preterm infants during the first 3 months and to investigate their insulin sensitivity and resistance. METHODS: We conducted an observational, longitudinal study. A total of 216 late preterm infants underwent body composition assessment using an air displacement plethysmograph at term and at 3 months of corrected age. In a subgroup of infants (n = 48) the blood glucose and insulin concentration were determined at term and insulin resistance (homeostasis model assessment for insulin resistance; HOMA-IR) and sensitivity (quantitative insulin sensitivity check index; QUICKI) were then calculated. The reference group comprised 71 healthy term infants. RESULTS: The mean birth weight and gestational age were 2,390 ± 391 g and 35.2 ± 0.8 weeks, respectively. At term the fat mass index (kg/m2) of late preterm infants, born adequate for their gestational age and small for their gestational age, was higher than that of term infants (2.08 ± 0.82 vs. 1.62 ± 0.64 vs. 1.03 ± 0.36, p < 0.005, respectively), whereas at 3 months of corrected age no difference was found among the groups. The mean values of glucose, insulin, HOMA-IR, and QUICKI were within the 5th and 95th percentiles. CONCLUSIONS: On the basis of these preliminary findings, fat mass accretion of late preterm infants appears not to be associated with perturbation of the glucose homeostasis.

No relative increase in intra-abdominal adipose tissue in healthy unstressed preterm infants at term.

BACKGROUND: Preterm infants may be at risk for altered adiposity, a known risk factor for unfavorable metabolic and cardiovascular outcomes. OBJECTIVES: The aim was to compare body composition (total body fat mass (FM), subcutaneous and intra-abdominal adipose tissue (AT)) between infants born preterm and at term. METHODS: We conducted an observational, cross-sectional study that involved 50 infants born preterm free from major co-morbidities and 34 term healthy breastfed infants. Anthropometric measurements, body composition (total body FM, subcutaneous and intra-abdominal AT) were assessed at 40-42 weeks postconceptional age for preterm infants and within 15 days of birth for term infants. Total body FM was assessed by an air displacement plethysmography system and subcutaneous abdominal and intra-abdominal AT were assessed by magnetic resonance imaging using a commercially available software program. RESULTS: Compared to term infants, mean (SD) total body FM (g) (636.7 (247) vs. 418.4 (253), p < 0.0001) and mean (SD) subcutaneous abdominal AT (g) (123 (36) vs. 98.9 (22), p < 0.001) were significantly higher in preterm infants but mean (SD) fat-free mass (g) (2,530 (420) vs. 2,965 (389), p < 0.0001) and mean (SD) intra-abdominal AT (10.9 (5.2) vs. 18.2 (13.2), p = 0.001) were significantly lower. CONCLUSIONS: In the absence of severe illness during the hospital stay, prematurity, although associated with increased total body FM, does not appear to be associated with a relative increase in intra-abdominal AT compared to term infants.