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AIM In 2009, the Italian society for paediatric nephrology suggested the need for cystography, following a first febrile urinary tract infection (UTI), only in children at high risk for dilating vesicoureteral reflux or in the event of a second infection. The aim of this study was to evaluate the adequacy of the risk factors proposed by the Italian guidelines. METHODS Children aged 2-36 months, managed by 10 Italian hospitals between 2009 and 2013, with a first febrile UTI were retrospectively evaluated. RESULTS Four hundred and fourteen children were included: 51% female, mean age eight months. Escherichia coli was responsible of 84% UTIs. 269 children (65%) presented at least one risk factor, thus were further investigated: 44% had a reflux. The presence of a pathogen other than E. coli significantly predicted high-grade reflux, both in the univariate (Odd Ratio 2.52, 95% Confidence Interval 1.32-4.81, p

ObjectiveTo estimate the prevalence of Joubert syndrome (JS) in Italy applying standards of descriptive epidemiology and to provide a molecular characterization of the described patient cohort.MethodsWe enrolled all patients with a neuroradiologically confirmed diagnosis of JS who resided in Italy in 2018 and calculated age and sex prevalence, assuming a Poisson distribution. We also investigated the correlation between proband chronological age and age at diagnosis and performed next-generation sequencing (NGS) analysis on probands' DNA when available.ResultsWe identified 284 patients with JS: the overall, female- and male-specific population-based prevalence rates were 0.47 (95% confidence interval [CI] 0.41–0.53), 0.41 (95% CI 0.32–0.49), and 0.53 (95% CI 0.45–0.61) per 100,000 population, respectively. When we considered only patients in the age range from 0 to 19 years, the corresponding population-based prevalence rates rose to 1.7 (95% CI 1.49–1.97), 1.62 (95% CI 1.31–1.99), and 1.80 (95% CI 1.49–2.18) per 100,000 population. NGS analysis allowed identifying the genetic cause in 131 of 219 screened probands. Age at diagnosis was available for 223 probands, with a mean of 6.67 ± 8.10 years, and showed a statistically significant linear relationship with chronological age (r2 = 0.79; p < 0.001).ConclusionsWe estimated for the first time the age and sex prevalence of JS in Italy and investigated the patients’ genetic profile. The obtained population-based prevalence rate was ≈10 times higher than that available in literature for children population.

In this paper we describe how an accurate urinary sediment examination, which revealed the presence of a severe 2,8-dihydroxyadenine crystalluria, opened the way to an articulate and successful diagnostic and therapeutic roadmap for a rare and potentially severe renal disease.

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.

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.

Summary Background Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. Methods The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. Results A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. Conclusions 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase. Patient subgroup (No. of renal units) All (168/168) Time interval Age > 36 months (40/168) Febrile UTI (33/168) Sensitivity, % (95% CI, %) 54 (46–62) 45 (34–56) 68 (52–82) 72 (60–82) Specificity, % (95% CI, %) 90 (84–94) 89 (79–94) 85 (70–94) 93 (84–98) Positive predictive value (PPV), % (95% CI, %) 79 (72–85) 68 (58–78) 81 (65–91) 93 (83–97) Negative predictive value (NPV), % (95% CI, %) 73 (66–80) 75 (64–83) 75 (58–87) 74 (61–83) Positive likelihood ratio (LR+) 5.3 4 4.8 10.83 Negative likelihood ratio (LR-) 0.51 0.62 0.37 0.3 Accuracy (%) 75 73 78 82 UTI, urinary tract infection; CI, confidence interval.

Background and objectives Information on ambulatory blood pressure monitoring (ABPM) in children is scarce. While in adults office BP (OBP) is higher than ABP and the difference increases as OBP increases, information in children suggests that at this young age ABP is no lower and often higher than OBP. This study was aimed at describing OBP-ABP differences in a cohort of children of different ages and BPs, and investigating whether OBP-ABP differences are dependent on age or OBP level. Methods We retrospectively compared OBP and 24-h, daytime and night-time ABP in 433 children and adolescents aged 4-18 years, referred to our hospital clinic. Results OBP was found to be significantly lower than 24-h and daytime ABP in the low age tertile (4-10 years) but not in the medium and high tertiles. OBP was also lower than ABP in normotensive patients (n = 182), but higher than ABP in untreated hypertensive patients (n = 92) despite similar ages. Continuous analyses showed a weak correlation of OBP-ABP differences with age, and a much stronger correlation with OBP so that 24-h ABP was higher than OBP at OBP values less than 117/73 mmHg and lower than OBP at higher OBP values. Logistic regression analysis indicates that also in children OBP accounts for most of the OBP-ABP difference. Conclusion There is a common relation both in children and adults between OBP and ABP. It is only because high OBP is common in the elderly, and the lowest OBP is usually found in young children that large positive OBP-ABP differences have been associated with old age, and negative differences with childhood. OBP-ABP differences, often defined as white-coat effect, can have different directions and are likely to be largely due to regression to the mean.

Alport syndrome (AS) is a progressive hereditary glomerular disease. Recent data indicate that aldosterone promotes fibrosis mediated by the transforming growth factor-β1 (TGF-β1) pathway, which may worsen proteinuria. Spironolactone (SP) antagonizes aldosterone and this study aimed to evaluate the efficacy of SP in reducing proteinuria and urinary TGF-β1 excretion in proteinuric AS patients.The study involved ten children with AS, normal renal function, and persistent proteinuria (6 months; uPr/uCr ratio1). SP 25 mg once a day for 6 months was added to existing ACE inhibitor treatment with or without angiotensin-II receptor blockade. Urine and blood samples were examined monthly. Urinary TGF-β1 levels were measured twice before and three times during SP treatment. Plasma renin activity (PRA) and serum aldosterone levels were also measured. In eight patients, uProt/uCreat was also assessed after 9 months and 12 months of SP treatment.After beginning SP therapy, all patients showed significant decrease in mean uProt/uCreat ratio (1.77 ± 0.8 to 0.86 ± 0.6; p 0.001) and mean urinary TGF-β1 levels (104 ± 54 to 41 ± 20 pg/mgCreatinine; p 0.01), beginning after 30 days of treatment and remaining stable throughout SP administration. PRA remain unchanged, and mean serum aldosterone increased from 105 ± 72 pg/ml to 303 ± 156 pg/ml (p 0.001). The only side effect was gynecomastia in an obese boy. After 1 year of therapy, mean uProt/uCreat remains low (0.82 ± 0.48).Addition of SP to ACE-I treatment with or without angiotensin II receptor blokers (ARB) significantly reduced proteinuria. This was mediated by decreased urinary TGF-β1 levels and not associated with major side effects.

We report the recommendations for the diagnosis, treatment, imaging evaluation and use of antibiotic prophylaxis in children with the first febrile urinary tract infection, aged 2 months to 3 years. They were prepared by a working group of the Italian Society of Pediatric Nephrology after careful review of the available literature and a consensus decision, when clear evidence was not available. Conclusion: These recommendations are endorsed by the Italian Society of Pediatric Nephrology. They can also be a tool of comparison with other existing guidelines in issues in which much controversy still exists.

Primary vesicoureteral reflux (VUR), one of the principal causes of chronic renal failure (CRF), occurs as a result of two distinct and sex-related mechanisms: congenital renal hypoplasia, which is prevalent in males, and acquired renal scarring in females. We used data from the ItalKid Project, a prospective population-based CRF registry of patients undergoing conservative treatment, to evaluate the gender distribution and severity of primary VUR, the age at diagnosis, and the diagnostic and therapeutic methods adopted in children with CRF. The prevalence of males (77.5%), the severity of VUR (grade IV-V), and the early age at diagnosis (18% prenatally) seem to suggest that congenital renal damage is the major cause of pediatric CRF.

Aim: Efforts are currently made to detect vesicoureteric reflux (VUR) early after urinary infections in order to limit secondary renal damage. This study investigated the extent to which recommendations for the detection of VUR are put into practice, and their influence on the age at diagnosis. Methods: The age at diagnosis of VUR after urinary tract infections was analysed in 126 patients (48M, 78F) referred to a tertiary centre in Milan between 1976 and 1999. Results: The median age at diagnosis was 34 mo in subjects born before and 8 mo (p < 0.001) in those born after 1988. The difference was statistically significant in female but not in male subjects. The figures from Milan were compared with those for 102 patients (35M, 65F) born between 1946 and 1970, treated in Melbourne and reported in 1976. In Melbourne the median age at diagnosis was 1–2 y for boys and 5–6 y for girls; in Milan, the corresponding figures were

Obstructive uropathy causes tubular resistance to aldosterone and severe metabolic imbalance may be precipitated by an episode of pyelonephritis. In the last 3 years we investigated 52 episodes of pyelonephritis (positive urine culture, elevated C reactive protein, fever, elevated neutrophil count) in 50 children between 15 days and 15 months of age. Ultrasonography voiding cystography and renal scintiscan were performed in all cases and i.v. urography in some. A salt-losing syndrome with hyponatremia and hyperkalemia (Na125 meq/liter; K6.3 meq/liter) was observed in 17 infants3 months, accompanied by plasma aldosterone concentration of 5000 to 23,000 pg/ml (normal value,1000 pg/ml). All these children had a severe urinary tract (UT) malformation (ureteropelvic junction stenosis in 7 cases, vesicoureteral reflux in 7, posterior urethral valves in 2, double system in 1). Thirteen infants3 months, 7 with no urinary tract malformations, did not have electrolyte imbalance. Pyelonephritis was diagnosed in 20 other patients ages 4 to 15 months, including 16 with severe UT malformations; 4 had normal UTs. We conclude that a salt-losing syndrome with tubular resistance to aldosterone can occur during pyelonephritis in young infants with congenital UT malformation, that the risk diminishes considerably or disappears after 3 months of age and that in the absence of UT malformation pyelonephritis does not cause acute sodium loss of clinical relevance.

The management of neonates with mild hydronephrosis diagnosed antenatally is still debated. Although some of these infants are normal, it is recognised that others will have mild obstruction of the ureteropelvic junction or vesicoureteric reflux (VUR). A prospective study was performed in all newborn infants with an antenatal diagnosis of mild hydronephrosis (47 babies, 62 kidneys) born over a two year period in order to assess the frequency of VUR. Voiding cystography in 14 patients with 21 renal units showed VUR. Two patients underwent surgery and the VUR resolved; the other 12 received medical treatment. Repeat cystography was scheduled for 12-18 months later, when a high rate of spontaneous cure was observed. The remaining patients were monitored by ultrasonography but only in one case did hydronephrosis deteriorate because of the presence of severe ureteropelvic junction obstruction. It is concluded that mild dilatation of the pelvis might be an expression of a potentially severe malformation such as VUR, and a careful follow up of these cases is mandatory.

We report the recommendations for the diagnosis, treatment, imaging evaluation and use of antibiotic prophylaxis in children with the first febrile urinary tract infection, aged 2 months to 3 years. They were prepared by a working group of the Italian Society of Pediatric Nephrology after careful review of the available literature and a consensus decision, when clear evidence was not available.These recommendations are endorsed by the Italian Society of Pediatric Nephrology. They can also be a tool of comparison with other existing guidelines in issues in which much controversy still exists.

We describe an infant affected by adenine phosphoribosyltransferase (APRT) deficiency diagnosed at 18 months of age with a de novo mutation that has not been previously reported. APRT deficiency is a rare defect of uric acid catabolism that leads to the accumulation of 2,8 dihydroxyadenine (2,8-DHA), a highly insoluble substance excreted by the kidneys that may precipitate in urine and form stones. The child suffered from renal colic due to a stone found in the peno-scrotal junction of the bulbar urethra. Stone spectrophotometric analysis allowed us to diagnose the disease and start kidney-saving therapy in order to avoid irreversible chronic kidney damage. APRT deficiency should always be considered in the differential diagnosis of pediatric urolithiasis.

Sirs, Many leading international scientific societies [European Society of Paediatric Nephrology (ESPN), International Society of Nephrology (ISN), International Pediatric Nephrology Association (IPNA), Latin American Pediatric Nephrology Association (ALANEPE) and others] and a significant number of pediatric nephrologists have contributed to the growth of our knowledge in the field of pediatric nephrology in developing countries over recent years [1–4]. Since 2000, we have been participating in a cooperative project in Nicaragua [5] with the aims of developing a tertiary pediatric nephrology centre in Managua (renal biopsies, dialysis and living donor transplantations) and a web network that links this centre and six Departmental hospitals in order to share diagnostic and treatment protocols and improve the early diagnosis and treatment of children with kidney and urinary tract diseases (KUTDs). The project includes the regular recording of the clinical data of all inand outpatients aged

Purpose: The nephropathy associated with vesicoureteral reflux (VUR) is one of the leading causes of chronic renal failure (CRF) in children. We describe the clinical course of the disease based on information available in the ItalKid Project database, and analyze the predictive value of baseline renal function, age at VUR diagnosis and urinary protein excretion in relation to the risk of progressive renal failure. Materials and Methods: As of December 31, 2001 the registry included a total of 343 patients (261 males) with a diagnosis of primary VUR, which was the leading single cause of CRF, accounting for 25.4% of all patients with CRF. Results: The estimated risk of end stage renal disease (ESRD) by age 20 years was 56%. The patients with a creatinine clearance (Ccr) of less than 40 ml per minute at baseline had an estimated 4-fold greater risk of ESRD developing in comparison with those whose Ccr was 40 to 75 ml per minute. No significant difference in probability of disease progression to ESRD was found between subjects diagnosed with VUR at age 6 months or less and those diagnosed later (older than 6 months). Furthermore, children with normal urinary protein excretion (a urinary protein [uPr]/urinary creatinine [uCr] ratio of less than 0.2 in 36 patients) and low grade proteinuria (uPr/uCr 0.2 to 0.8 in 34 patients) at baseline showed a significantly slower decrease in mean Ccr than those with moderate proteinuria (uPr/uCr greater than 0.8 in 34 patients). Hypertension and/or antihypertensive treatment (including antiprogressive drugs) were reported in 29.1% of patients. Conclusions: The results of the present study define the long-term risk of ESRD in a large population of children with CRF and VUR, and provide some critical information for identifying the prognosis.

Background Efforts are now routinely made for early detection of vesicoureteric reflux after urinary tract infections in order to limit secondary renal damage. Methods The age at diagnosis of reflux after urinary tract infections was analysed in 162 Swiss patients (46 boys and 116 girls) referred by primary care physicians to the Division of Paediatric Nephrology, University of Bern, Switzerland between 1978 and 1999. The figures noted in Switzerland were also compared with those noted in 102 Australian patients (35 boys and 67 girls) reported by Lenaghan in 1976. Results In Switzerland the median age at diagnosis was 23 months in 74 subjects diagnosed between 1978 and 1988 and 10 months in 88 subjects diagnosed between 1989 and 1999. The difference was statistically significant in girls but not in boys. In Australia the median age at diagnosis was 15 months for boys and 78 months for girls; in Switzerland, the corresponding figures were 12 and 29 months (between 1978 and 1988), respectively 5 and 14 months (between 1989 and 1999). The difference between Australia and Switzerland was statistically significant in girls but not in boys. Conclusions In Switzerland vesicoureteric reflux is now detected earlier than in the past. This trend is more marked in girls than in boys but the detection of reflux is still earlier in boys than in girls.

Objective. The ItalKid Project is a pro- spective, population-based registry that was started in 1990 with the aim of assessing the epidemiology of child- hood chronic renal failure (CRF), describing the natural history of the disease, and identifying factors that influ- ence its course. This article reports the epidemiologic results. Methods. Prevalent and incident cases of CRF in chil- dren and adolescents were identified throughout Italy (total population base: 16.8 million children) by regularly asking all of the pediatric hospitals and adult nephrology units potentially involved in caring for children with kidney disease to report all cases that meet the inclusion criteria and then to update the clinical information re- garding all previously reported patients on an annual basis. The inclusion criteria were 1) creatinine clearance (Ccr; according to Schwartz's formula)

The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration.

The relations between renal hemodynamics (Inutest, CPAH) and sodium segmental handling (sodium distal delivery, distal reabsorption, and fractional excretion) were studied in 9 healthy adults infused with an isotonic amino acid solution and in 6 subjects infused with 0.9% saline for 3 h at 0.2 ml/min/kg. During all tests maximal water diuresis was induced and maintained to effect analysis of sodium segmental transport. Both types of infusion produced a similar expansion of extracellular volume (weight increase, hematocrit fall, suppressed plasma renin activity and plasma aldosterone). The amino acid infusion increased the glomerular filtration rate (GFR) and renal blood flow without modifying the filtration fraction. With saline no hemodynamic modifications were observed. The expansion with saline depressed proximal and distal sodium reabsorption whereas during amino acid infusion sodium distal delivery was unaltered and the significantly increased sodium fractional excretion was sustained only by depressed distal reabsorption. Therefore, in parallel with the GFR increase, closely dependent on renal vasodilatation, the well-known stimulation of sodium cotransport by amino acids is able to antagonize the effects of expansion on the proximal sodium reabsorption. An explanation of glomerular hyperfiltration based on a primary metabolic stimulation of the proximal tubular function is suggested.