Clinical implications of primary "occult" vesicoureteral reflux in male children.

OBJECTIVES: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. MATERIALS AND METHODS: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. RESULTS: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. CONCLUSION: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. CLINICAL RELEVANCE STATEMENT: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention.

Primary non-refluxing megaureter: Natural history, follow-up and treatment.

Primary non-refluxing megaureter (PMU) is a congenital dilation of the ureter which is not related to vesicoureteral reflux, duplicated collecting systems, ureterocele, ectopic ureter, or posterior urethral valves and accounts for 5 to 10% of all prenatal hydronephrosis (HN) cases. The etiology is a dysfunction or stenosis of the distal ureter. Most often PMU remains asymptomatic with spontaneous resolution allowing for non-operative management. Nevertheless, in selective cases such as the development of febrile urinary tract infections, worsening of the ureteral dilatation, or reduction in relative renal function, surgery should be considered. CONCLUSION: Ureteral replantation with excision of the dysfunctional ureteral segment and often ureteral tapering is the gold-standard procedure for PMU, although endoscopic treatment has been shown to have a fair success rate in many studies. In this review, we discuss the natural history, follow-up, and treatment of PMU. WHAT IS KNOWN: • PMU is the result of an atonic or stenotic segment of the distal ureter, resulting in congenital dilation of the ureter, and is frequently diagnosed on routine antenatal ultrasound. WHAT IS NEW: • Most often, PMU remains asymptomatic and clinically stable, allowing for non-operative management. • Nevertheless, since symptoms can appear even after years of observation, long-term ultrasound follow-up is recommended, even up to young adulthood, if hydroureteronephrosis persists. • Ureteral replantation is the gold standard in case surgery is needed. In selected cases, however, HPBD could be a reasonable alternative.

Indirect signs of infravesical obstruction on voiding cystourethrography improve post-neonatal posterior urethral valves detection rate.

OBJECTIVES: To identify the diagnostic performance of clinical and radiological signs (on voiding cystourethrography [VCUG]) to detect posterior urethral valves (PUV) in the post-neonatal period. MATERIALS AND METHODS: One hundred eighteen males (median age = 0.8 years, range = 1 month-14 years, 48 toilet-trained) undergoing VCUG in a 2-year period were prospectively enrolled. Direct (dilated posterior urethra) and indirect (hypertrophied bladder neck, musculus interuretericus hypertrophy, and trabeculated appearance of the bladder wall) PUV signs on VCUG were assessed. Uroflowmetry was defined pathological by patterns suggesting infravesical obstruction. RESULTS: Twenty-two patients with direct, 28 with indirect PUV signs on VCUG, and one with normal VCUG but persisting micturition symptoms with pathological uroflowmetry underwent urethrocystoscopy and in 43/51 a PUV diagnosis was made (n = 22, 51.2%, with direct PUV signs). In 8/28 patients with indirect signs, PUV were not confirmed. Among non-toilet-trained patients, none of the clinical signs/symptoms was associated with PUV while among toilet-trained patients only pathological uroflowmetry (odds ratio, OR = 4.0 [95% confidence interval:1.2-13.2; p = 0.02]) and pathological uroflowmetry with history of urinary tract infection (OR = infinity) were significantly associated with PUV. Significant associations with PUV of direct and indirect signs on VCUG were found both in toilet-trained and non-toilet trained patients. Direct PUV sign had 100% specificity and sensitivity while indirect PUV signs showed sensitivity = 58.1% and specificity = 89.3%. The absence of any radiological sign had a negative predictive value = 98.5%. CONCLUSION: Only half of patients with endoscopy-confirmed PUV presents with direct sign of PUV on VCUG. Accounting for indirect PUV signs on VCUG and pathological uroflowmetry (in toilet-trained children) could improve the PUV detection rate. CLINICAL RELEVANCE STATEMENT: Indirect radiological PUV signs should be valorized when interpreting VCUG to improve the PUV detection rate. The absence of any radiological PUV (direct and indirect) sign on VCUG excludes PUV with a very high negative predictive value. KEY POINTS: • Worldwide agreement is that a non-dilated urethra on voiding cystourethrography excludes obstruction. • Half of patients with posterior urethral valves have non-dilated urethra on voiding cystourethrography. • Accounting for indirect signs of posterior urethral valves on voiding cystourethrography improves the diagnostic performance.

Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux.

BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

Early Renal Ultrasound in Congenital Solitary Kidney May Help to Select Patients at Lower Risk of Associated Vesicoureteral Reflux.

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/cysto-scintigraphy. 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.

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.

From Skin to Kidneys: Cutaneous Clues of Renal Disease in Children.

BACKGROUND: The skin is often seen as a world apart, but not rarely do cutaneous manifestations reveal signs of systemic disease. OBJECTIVES: The aim of this review is to include in one paper all the possible correlations between nephrological and dermatological manifestations of the same disease in pediatric patients while also keeping in mind that in apparent exclusively dermatological diseases there can be nephrological manifestations as part of the same disorder and vice versa. METHODS: We searched on PubMed for a possible link between skin and kidney matching the following terms and correlated MeSH terms: dermatology, skin, kidney, renal disease, nephrology, pediatrics, child, childhood, vasculitis, and cancer. We selected only articles reporting a link between nephrology and dermatology in pediatrics, and they are all included in this comprehensive review. RESULTS: Kawasaki disease, Henoch-Schönlein purpura, systemic lupus erythematosus, Dent disease, subcutaneous fat necrosis, Langerhans cell histiocytosis, renal cell carcinoma, non-Hodgkin lymphoma, tuberous sclerosis complex and syndromes with increased risk for Wilms tumor, Fabry disease, nail-patella syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Adams-Oliver syndrome 1, Apert syndrome, Fanconi pancytopenia syndrome, Pallister-Hall syndrome, and Fanconi pancytopenia syndrome are all conditions in which there can be both nephrological and dermatological manifestations in children. CONCLUSIONS: We could not find any reports that focused attention on the link between nephrological and dermatological manifestations of the same disease in children. It is also important for clinicians to keep in mind that in what may appear to be an exclusively dermatological disease, there can be nephrological manifestations as part of the same disorder and vice versa.

Hematuria at dipstick on first versus second morning voiding: A screening for patients with persistent isolated hematuria?

BACKGROUND: In our clinical practice we observed that -differently from patients with defined glomerulopathies- children with persistent isolated microscopic hematuria (PImH) usually shows at dipstick on first compared with second morning voiding lower degree of hematuria. We hypothesized that comparison of hematuria degree between first and second morning voiding (dipstick comparison test) could help in selection of patients needing of specific investigations. In this study, we aimed preliminarily validating our hypothesis. METHODS: To define the risk of active glomerulopathies we used patients with defined glomerulopathies as cases. We prospectively enrolled 103 children during a one-year period. Sixty-nine of them had PImH, 16 microscopic/macroscopic hematuria (mMH), and 18 defined glomerulopathies. Inclusion criteria were: 1) persistent microscopic hematuria (≥1+ at dipstick) with or without defined glomerulopathy and/or previous episodes of macroscopic hematuria; 2) for the patients without defined glomerulopathy, having made regular biannual follow-up visits for at least 2 years in our department; 3) normal renal function and blood pressure at enrollment visit. We compared hematuria degree between first and second morning voiding. Possible findings were absence (NH), less degree (LH), similar degree (SH), and higher degree (HH) of hematuria in the first compared with second voiding. RESULTS: At dipstick comparison test, 27.2% of patients presented NH, 44.7% LH, 28.1% SH, and none HH. NH showed specificity and PPV of 100% and significant area under receiver operating characteristic curve (AUROC = 0.66; 95%CI:0.55-0.78; p = 0.03) for absence of defined glomerulopathies. LH showed better sensitivity (76.9% Vs 33%) and NPV (78.9% Vs 24%) and lower specificity (88.2% Vs 100%) and PPV (87.0% Vs 100%) than NH for absence of defined glomerulopathies. Moreover, the LH showed a non-significant AUROC curve for presence of defined glomerulopathies. SH showed specificity of 80%, NPV of 91.9% and significant AUROC curve for presence of defined glomerulopathies (0.67; 95%CI:0.55-0.80; p = 0.009). The ROC curve analysis examining the delta of hematuria degree comparing first with second morning urine voiding showed a significant AUROC curve (AUROC = 0.78; 95%CI,0.68-0.89; p = 0.0002) with delta ≤ 1 showing the best sensitivity (80%) and specificity (66.7%) for defined glomerulopathies. None of the patients with defined glomerulopathies presented NH. Having SH presented relative risk for defined glomerulopathy of 5.1 (95%CI:1.9-13.6; p = 0.0007). Conversely, taken together NH and LH the RR was 0.2 (95%CI 0.1-0.5; p = 0.0007). INTERPRETATIONS: The dipstick on the first urine voiding underestimates the hematuria in about 70% of patients. The dipstick comparison test might easily screen patients with PImH and mMH needing of further investigations and treatment.

Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation.

Nephrogenic diabetes insipidus (NDI) is a rare tubulopathy characterized by urinary concentration defect due to renal resistance to vasopressin. Loss-of-function mutations of vasopressin V2 receptor (V2R) gene (AVPR2) is the most common cause of the disease. We have identified five novel mutations L86P, R113Q, C192S, M272R, and W323_I324insR from NDI-affected patients. Functional characterization of these mutants revealed that R113Q and C192S were normally localized at the basolateral membrane of polarized Madin-Darby Canine Kidney (MDCK) cells and presented proper glycosylation maturation. On the other side, L86P, M272R, and W323_I324insR mutants were retained in endoplasmic reticulum and exhibited immature glycosylation and considerably reduced stability. All five mutants were resistant to administration of vasopressin analogues as evaluated by defective response in cAMP release. In order to rescue the function of the mutated V2R, we tested VX-809, sildenafil citrate, ibuprofen and tolvaptan in MDCK cells. Among these, tolvaptan was effective in rescuing the function of M272R mutation, by both allowing proper glycosylation maturation, membrane sorting and response to dDAVP. These results show an important proof of concept for the use of tolvaptan in patients affected by M272R mutation of V2R causing NDI.

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).

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.

Transmembrane 6 superfamily member 2 167K allele improves renal function in children with obesity.

BACKGROUND: The transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphism influences estimated glomerular filtration rate (eGFR) in adults without diabetes and without obesity. We aimed exploring the impact of this polymorphism on eGFR in children with obesity with and without non-alcoholic fatty liver disease (NAFLD). METHODS: We genotyped 531 children with obesity for TM6SF2 E167K polymorphism. NAFLD was defined by ultrasound detected liver steatosis and/or ALT > 40 IU/L. RESULTS: Patients carrying the TM6SF2 167K allele showed higher eGFR levels compared with E167 homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with TM6SF2 genotype both in patients with and without NAFLD. This association, however, was stronger in patients with NAFLD. CONCLUSIONS: Children with obesity carrying the TM6SF2 167K allele show higher eGFR levels compared with E167 allele homozygous subjects, independently of NAFLD. A major effect of this polymorphism in the presence of NAFLD was captured.

Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children.

AIM: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. METHODS: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. RESULTS: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. CONCLUSION: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking.

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.

Nephrogenic Diabetes Insipidus in Childhood: Assessment of Volume Status and Appropriate Fluid Replenishment.

Patients affected by nephrogenic diabetes insipidus (NDI) can present with hypernatremic dehydration, and first-line rehydration schemes are completely different from those largely applied in usual conditions determining a mild to severe hypovolemic dehydration/shock. In reporting the case of a patient affected by NDI and presenting with severe dehydration triggered by acute pharyngotonsillitis and vomiting, we want to underline the difficulties in managing this condition. Restoring the free-water plasma amount in patients affected by NDI may not be easy, but some key points can help in the first line management of these patients: (1) hypernatremic dehydration should always be suspected; (2) even in presence of severe dehydration, skin turgor may be normal and therefore the skinfold recoll should not be considered in the dehydration assessment; (3) decreased thirst is an important red flag for dehydration; (4) if an incontinent patient with NDI appears to be dehydrated, it is important to place the urethral catheter to accurately measure urine output and to be guided in parenteral fluid administration; (5) if the intravenous route is necessary, the more appropriate fluid replenishment is 5% dextrose in water with an infusion rate that should slightly exceed the urine output; (6) the 0.9% NaCl solution (10 mL/kg) should only be used to restore the volemia in a shocked NDI patient; and (7) it could be useful to stop indomethacin administration until complete restoration of hydration status to avoid a possible worsening of a potential prerenal acute renal failure.

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.