From Clinical Scenarios to the Management of Lower Urinary Tract Symptoms in Children: A Focus for the General Pediatrician.

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.

Combination therapy (desmopressin plus oxybutynin) improves the response rate compared with desmopressin alone in patients with monosymptomatic nocturnal enuresis and nocturnal polyuria and absence of constipation predict the response to this treatment.

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. WHAT IS KNOWN: • Combination therapy (CT) (desmopressin plus anticholinergic drug) has been described as a therapeutic option for patients with monosymptomatic nocturnal enuresis (MNE) not responding to desmopressin alone as first-line treatment. • Variable protocols and variable combination of drugs have been described with a response rate ranging from 44 to 76%. WHAT IS NEW: • We found that 59 patients (75.6%) treated with evening administration of 240 mcg of sublingual desmopressin plus 0.3-0.5 mg/kg of oxybutynin had an improvement of response compared to treatment with desmopressin alone. • We add evidence that presence of frequently recurring nocturnal polyuria and absence of constipation are predictors of response to CT.

Euthyroid sick syndrome and its association with complications of type 1 diabetes mellitus onset.

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 <85% and/or fractional excretion of Na>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.

Diagnostic Performance of the Acute Kidney Injury Baseline Creatinine Equations in Children and Adolescents with Type 1 Diabetes Mellitus Onset.

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.

Early Renal Ultrasound in Patients with Congenital Solitary Kidney Can Guide Follow-Up Strategy Reducing Costs While Keeping Long-Term Prognostic Information.

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.

Heart rate cut-offs to identify non-febrile children with dehydration and acute kidney injury.

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 < 0.001) and the best EHRV cut-off was > 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.

Acute Kidney Injury and Renal Tubular Damage in Children With Type 1 Diabetes Mellitus Onset.

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 < 85% and/or fractional excretion of Na (FENa) > 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa < 1%, and acute tubular damage (ATD) by RTD without AKI. 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.

How to interpret symptoms, signs and investigations of dehydration in children with gastroenteritis.

Dehydration is a significant cause of morbidity and mortality in children worldwide. Infants and young children are vulnerable to dehydration, and clinical assessment plays a pivotal role in their care. In addition, laboratory investigations can, in some children, be helpful when assessing the severity of dehydration and for guiding rehydration treatment. In this interpretation, we review the current literature and provide an evidence-based approach to recognising and managing dehydration in children.

Congenital Solitary Kidney from Birth to Adulthood.

PURPOSE: 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. MATERIALS AND METHODS: 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 rate <90 ml/minute/1.73 m2 and/or 24-hour ambulatory blood pressure monitoring confirmed hypertension and/or proteinuria. Modifiable risk factors and congenital anomalies of the kidney and urinary tract (CAKUT) of congenital solitary functioning kidney were evaluated as risk factors for kidney injury. RESULTS: The 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). CONCLUSIONS: 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.

A Particular Form of "Urolithiasis" in a Toddler.

Milk of calcium is a viscous colloidal suspension of calcium salts that forms in dilated cysts or cavities. We present, for the first time in literature, a toddler with isolated milk of calcium and treated with a conservative approach. A boy with a history of one urinary tract infection and recurrent fever without vesicoureteral reflux showed at the age of 14 months a left obstructive staghorn stone. Because of absent function of the left kidney at mercapto acetyl tri glycine scintigraphy, a JJ stent was positioned with a leak of whitish material immediately after the stent positioning. Renal scintigraphy performed 1 month later revealed a partial resumption in renal function (18%). When he was 18 months old, the child suffered episodes of acute pain with inconsolable crying, unresponsive to paracetamol administration. Ultrasound assessment revealed left pelvic dilation (anterior-posterior diameter of 18 mm), suspended echogenic debris in the bladder, and dilated left distal ureter with particulate matter. These episodes of acute pain were followed by expulsion of numerous soft formations and emission of greenish urine. Both urine culture at the admission and culture on the greenish urines were sterile. After the expulsion of the soft formations, pain episodes stopped. The diagnosis of milk of calcium stone was made. With this case, we highlight a condition that can be easily diagnosed (if known) because the morphology of the expelled material is pathognomonic. Diagnosing it could avoid unnecessary treatments (ie, extracorporeal shockwave lithotripsy) and support a conservative approach (ie, stent positioning).

Asymptomatic intracranial aneurysms in beta-thalassemia: a three-year follow-up report.

BACKGROUND: No information is currently available regarding the natural history of asymptomatic intracranial aneurysms in beta-thalassemia, raising several concerns about their proper management. METHODS: We performed a prospective longitudinal three-year-long MR-angiography study on nine beta-thalassemia patients (mean-age 40.3 ± 7.5, six females, 8 transfusion dependent) harboring ten asymptomatic intracranial aneurysms. In addition, we analyzed the clinical files of all adult beta-thalassemia patients (160 patients including those followed with MR-angiography, 121 transfusion dependent) referring to our Centers between 2014 and 2019 searching for history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. RESULTS: At the end of the three-year-long follow-up, no patient showed any change in the size and shape of the aneurysms, none presented new intracranial aneurysms or artery stenoses, none showed new brain vascular-like parenchymal lesions or enlargement of the preexisting ones. Besides, in our database of all adult beta-thalassemia patients, no one had history of subarachnoid hemorrhage or history of symptomatic intracranial aneurysms. CONCLUSIONS: Incidental asymptomatic intracranial aneurysms do not seem to be associated, in beta-thalassemia, with an increased risk of complications (enlargement or rupture) at least in the short term period, helping to optimize human and economic resources and patient compliance during their complex long-lasting management.

Interrater reliability of bladder ultrasound measurements in children.

INTRODUCTION: Bladder ultrasound is becoming pivotal in the management and treatment of lower urinary tract dysfunction. There is a paucity of data regarding intra-observer and interobserver reliability of bladder ultrasound, especially in children. A previous study assessed interobserver agreement for both the postvoid residual volume and measurement of the bladder dimensions in adults showing excellent agreement. OBJECTIVE: To examine the interobserver and intra-observer reliability of bladder wall thickness, bladder urinary and postvoid residual urinary volume using ultrasound evaluated by paediatricians having different training levels. STUDY DESIGN: Four sonographers, 3 pediatric trainees and one experienced pediatric urologist measured the full bladder volume, the voiding residual volume, and the bladder wall thickness. Each sonographer made 3 measurements of each parameter. We assessed the interobserver and intra-observer variability by using intraclass correlations (ICCs). ICCs were calculated and tested with a significance level of 5%. The interrater ICC was calculated from the mean of the three measurements of each variable (full bladder volume, postvoid residual, bladder wall thickness). ICC ≥0.75 was considered excellent. Bland-Altman plots were also used to assess the interobserver agreement. RESULTS: Sixty children were recruited (7.3 ± 1.1 years). The interobserver ICCs for bladder volume and voiding residual volume were 0.91 (confidence interval 0.85-0.95) for both. The interobserver ICCs for the bladder wall thickness was satisfactory 0.43, with a minimum detectable difference of 2 mm. The observed values for intra-observer analysis showed an excellent (ICC ≥ 0.90) agreement between the three measurements performed by each one of the sonographers. Bland-Altman plots showed that the bias (mean difference) was -0.35 and the limits of agreement were -3.43 and 2.73 for the bladder wall thickness measurements (Figure). DISCUSSION: The interobserver reliability for both the postvoid residual volume and full bladder volume were excellent even in operators with different levels of training, pointing out the role of bladder ultrasound in the routine clinical practice. Weaker agreement was found for the bladder wall thickness measurement. The intra-observer agreement was excellent for all the measurements. CONCLUSION: These results showed a good reliability of urinary bladder ultrasound in children aged 7.3 ± 1.1 years as far as bladder volume measurement is concerned. Given the variability of bladder wall thickness, a standardized methodology is desirable to increase its reliability.

Pilot study showed that poor feeding, especially with leucocyturia, increased the odds of non-febrile urinary tract infections in children who were not toilet trained.

AIM: This study assessed the prevalence of wrongly diagnosed non-febrile urinary tract infections in patients who had not been toilet trained and presented with poor feeding and, or, failure to thrive. The diagnostic value of these signs in predicting non-febrile UTIs was also explored. METHODS: We focused on 59 outpatients (56.7% male) with these criteria, who had positive urine cultures and were referred to our Italian University hospital from January 2017 to January 2019. None were on antibiotics and all underwent urine cultures by bladder catheterisation. Wrongly diagnosed non-febrile UTIs were defined by sterile urine cultures. The predictive value was evaluated using logistic regression. RESULTS: The mean age was 8.5 ± 5.7 months and 72.9% had wrongly diagnosed non-febrile UTIs. Poor feeding was significantly higher among the 16 patients with true non-febrile UTIs (P = .04). It was significantly predictive of non-febrile UTIs (odds ratio 4.1, 95% confidence interval 1.1-16.6), especially when leucocyturia was present (odds ratio 9.7, 95% confidence interval 2.3-40.7). CONCLUSION: Wrongly diagnosed non-febrile UTIs were high in children with poor feeding and, or, failure to thrive. Only poor feeding and, in particular, the combination of poor feeding and leucocyturia, significantly increased the odds of non-febrile UTI.

Effect of Body Mass Index on Estimated Glomerular Filtration Rate Levels in Children With Congenital Solitary Kidney: A Cross-Sectional Multicenter Study.

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<2.5 kg, age, BMI-SDS, SBP-SDS, DBP-SDS, RL-SDS (renal length), and presence of kidney injury at last follow-up as covariates. RESULTS: The eGFR levels reduced gradually from underweight to obese patients (P = .047). The eGFR levels significantly increased across first and second tertiles of duration of overweight/obesity while they decreased across second and third tertiles of duration of overweight/obesity (P = .005). The eGFR and BMI-SDS at last follow-up were indirectly correlated (coefficient = -0.30, r2 = 9.2%, P = .0004). A general linear model for eGFR variance (model R2 = 26.37%; P = .02) confirmed an indirect and significant association of eGFR values with BMI-SDS as the only significant finding. CONCLUSIONS: In patients with CSK, the higher the BMI-SDS and the duration of overweight/obesity, the lower the eGFR levels. Primary prevention strategies to counteract overweight/obesity are mandatory in CSK patients.

In children with urinary tract infection reduced kidney length and vesicoureteric reflux predict abnormal DMSA scan.

BACKGROUND: To evaluate sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of renal ultrasonography (US) in predicting renal uptake defects or reduced renal function at Tc-99m dimercaptosuccinic acid (DMSA) scan (primary outcome). We also evaluated which factors could be associated with Tc-99m DMSA renal scan anomalies. METHODS: We retrospectively included all the patients with vesico-ureteral reflux (VUR) undergoing the first Tc-99m DMSA renal scan within 3 months from the most recent renal US between 2016 and 2018. RESULTS: Sensitivity, specificity, PPV, and NPV of US in predicting abnormal Tc-99m DMSA scan were 38.9%, 91.5%, 71.9%, and 72.9%, respectively. Different length between the kidneys, expressed as standard deviation score (SDS), showed an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60-0.80; p < 0.0001) when evaluated as predictor of abnormal Tc-99m DMSA scan. A different length between the two kidneys >1.11 SDS had 91.5% sensitivity and 57.6% specificity. At multivariate analysis, the factors with significantly increased odds ratio of abnormal Tc-99m DMSA scan were difference in length between two kidneys >1.11 SDS and dilated VUR. CONCLUSIONS: The Tc-99m DMSA scan remains the gold standard to detect renal parenchymal anomalies. A different length between the kidneys >1.11 SDS and dilated VUR are predictors of abnormal Tc-99m DMSA renal scan.

Nonalcoholic fatty liver disease and eGFR levels could be linked by the PNPLA3 I148M polymorphism in children with obesity.

BACKGROUND: PNPLA3 I148M polymorphism has an effect on modulation of estimated glomerular filtration rate (eGFR) in nonobese nondiabetic adults and in children with histologically confirmed nonalcoholic fatty liver disease (NAFLD). OBJECTIVES: The objective of the study is to explore the impact of PNPLA3 I148M polymorphism on eGFR in children with obesity with and without NAFLD. METHODS: We genotyped 591 patients with obesity for PNPLA3 I148M polymorphism. Anthropometrical, biochemical, and instrumental data were collected. NAFLD was defined by the presence of ultrasound-detected liver steatosis and/or ALT levels greater than 40 IU/L. RESULTS: Patients with NAFLD showed significantly lower eGFR levels compared with subjects without NAFLD. Children with PNPLA3 MM genotype showed lower eGFR levels compared with those with either PNPLA3 IM or II genotypes both in the presence and absence of NAFLD. A general linear model for eGFR variance, including gender, duration of obesity, PNPLA3 genotypes, HOMA, BMI-SDS, LDL-C, and triglycerides as covariates, confirmed an inverse association between eGFR and PNPLA3 genotype only in the presence of NAFLD. CONCLUSIONS: Children with obesity and PNPLA3 MM genotype show lower eGFR levels compared with other genotypes, with a major effect of this polymorphism in the presence of NAFLD.

Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values.

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.

Chronic recurrent multifocal osteomyelitis: a case report.

BACKGROUND: Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic nonbacterial osteomyelitis, is a rare, noninfectious inflammatory disorder that causes multifocal bone lesions with swelling and pain. Lytic and sclerotic bone lesions could be found on X-ray. Short tau inversion recovery magnetic resonance imaging (STIR MRI) shows bone marrow oedema, bone expansion, lytic areas and periosteal reaction. CRMO is characterized by periodic exacerbations and remissions of unclear/unknown pathogenesis. CASE PRESENTATION: A 10 years old girl, suffering from pain in her right shoulder since the age of 9 years presented to our Department. Thanks to clinical data, laboratoristic and radiological findings and bone biopsy CRMO was diagnosed. So patient started anti-inflammatory treatment and her conditions improved. CONCLUSIONS: In a child with bone pain should be considered also rare condition as CRMO to perform a correct diagnosis and start an adequate treatment avoiding complications such as bone damage. This condition should be suspected in a child with recurrent bone pain, modest increase of inflammatory indices, lytic or sclerotic bone lesion on X Ray. Typical CRMO localizations are metaphyses of long bones, pelvis, clavicle, vertebral column, sternum, ribs, jaw, but any bone can be involved. The most common CRMO differential diagnosis is represented by infections, malignant bone tumors, Langerhans Cells Histiocytosis (LCH).