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Posterior reversible encephalopathy syndrome (PRES) is a variable etiology clinical syndrome with similar neuroimaging results and clinical symptoms. PRES can develop in both adults and children and is characterized by headaches, disorders of consciousness, seizures and especially focal visual disturbances, often associated with hypertensive state. In most cases, symptoms resolve without neurological consequences. The treatment strategy concerns early diagnosis and general measures to correct the underlying cause of PRES. Here, we report a case of PRES that occurs in a 6-year-old child with nephrotic syndrome.

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

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition characterized by headache, nausea, vomiting, seizures, and visual disturbances with typical radiological features of symmetrical edema mostly involving the white matter in the occipital regions (1–2). PRES can develop in association with a wide array of clinical conditions, including systemic infections, hypertension, organ transplantation, and immunosuppression (especially with calcineurin inhibitors). Children who are on prolonged steroid therapy or on calcineurin inhibitor therapy in nephrotic syndrome (NS) are at risk of developing PRES (3–4). A 6-year-old Moroccan-boy, followed in his country for nephrotic syndrome, was hospitalized in our unit of pediatrics for severe generalized body edema, proteinuria (18600 mg/day), low serum albumin (0.9 g/L), high serum cholesterol (468 mg/dl). His arterial blood pressure value was 122/77 mmHg. We treated him with steroid intravenous, albumin supplementations and we continued cyclosporine. While his general conditions were improving, on the seventh day of hospitalization he developed headache, vomiting, dizziness, temporal blindness. A non-contrast computerized tomography was performed and it showed symmetrical hypodensities in parieto-occipital regions. His blood pressure was 132/71 mmHg. Then he developed two episodes of generalized tonic clonic convulsion, followed by unconsciousness. Magnetic resonance imaging (MRI) showed hyperintense signal in the parieto-occipital regions, and revealed bilateral cortical and subcortical white matter edema in parieto-occipital lobes The child was treated with antihypertensive medications, diuretic, steroids and immunosuppressant (cyclosporine A), thereafter he got no seizure and regained full consciousness and vision. His blood pressure was kept at normal range and urinary protein excretion gradually decreased. MRI performed two weeks later revealed no abnormality of the brain, which is a usual phenomenon in case of PRES The pathophysiology of PRES remains controversial, and two main hypotheses have been suggested; impaired cerebral autoregulation resulting in increased cerebral blood flow, and endothelial dysfunction with cerebral hypoperfusion (5–6). PRES must be managed carefully and its pathogenic factors should be suspected and recognized as soon as possible in order to properly treat the patient. In hypertension-related and drug-induced PRES, in fact, effective management includes prompt withdraw of offending agent, aggressive control of blood pressure, timely anti-convulsant therapy. In our case, hypertension was undoubtedly an important cause, but we were uncertain whether cyclosporine also played a pathogenic role. PRES should be always considered in the differential diagnosis of a child with idiopathic nephrotic syndrome, headache and visual disturbance.

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.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.

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.

Summary Background and objectives Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission. Design, setting, participants, & measurements This open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m 2 intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome. Results Fifty-four children (mean age 11 4 years) with INS dependent on prednisone and calcineurin inhibitors for 12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P 0.001); 50% of RTX cases were in stable remission without drugs after 9 months. Conclusions Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal. Clin J Am Soc Nephrol 6: 1308–1315, 2011. doi: 10.2215/CJN.09421010

In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of 3 years. Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and 2-year-remission probabilities were, respectively, 20 and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months, respectively, following the first and subsequent courses. The time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20, or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor–sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.

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.