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Percutaneous transluminal renal angioplasty (PTRA), the recommended treatment in children with renovascular hypertension (RVH), often has unsatisfactory outcomes. Cutting balloons may improve the results of angioplasty in different vascular beds with complex and resistant lesions. We retrospectively analysed the effects of percutaneous cutting balloon angioplasty (PCBA) on blood pressure, cardiac mass and renal artery acceleration time in children/adolescents referred to our centre for RVH.Thirteen patients (aged 9-19 years) with renal artery stenosis (RAS) and severe hypertension were identified. RASs were focal fibromuscular (FMD) or FMD-like dysplasia (in six cases bilateral, in five associated with mid aortic syndrome). Ten patients had uncontrolled hypertension, in nine cases associated with left ventricular hypertrophy (LVH). Acceleration time was abnormal in all stenotic arteries. Eighteen PCBA were performed, in three arteries associated with stent implantation.PCBA was technically successful in all individuals without major complications. In one patient, an intra-stent restenosis occurred, successfully redilated with conventional angioplasty without recurrence at 4 years distance. One year after PCBA, mean SBP and DBPs were markedly reduced from 146 ± 25 to 121 ± 10 mmHg and from 87 ± 11 to 65 ± 12 mmHg, respectively ( P 0.001 for both). At that time, hypertension was cured in seven children and controlled in five individuals. This favourable outcome was confirmed with ambulatory blood pressure measurement in four patients. At the latest follow-up, left ventricular mass and acceleration time were normal in all patients.PCBA proved to be a well tolerated and effective procedure that can be considered as an alternative to PTRA to treat hypertensive children/adolescents with recurrent or resistant RAS.

Background Single mutations in COL4A3/COL4A4 genes have been described in patients with autosomal dominant Alport syndrome and thin basement membrane nephropathy, without a shared definition of these patients within the medical community. We aimed to better categorize this clinical entity by examining clinical manifestations, family history, pathological features and genetics. Methods We retrospectively analyzed patients with causative heterozygous COL4A3/COL4A4 mutations referred to us between 1990 and 2019. Index cases were defined as children who were the first to be diagnosed in their families. Results The study included 24 index cases and 29 affected relatives, belonging to 25 families with a heterozygous mutation in the COL4A3/COL4A4 genes. During the follow-up, nine patients developed proteinuria [median age 15.7 years (range 5.6–33)], six at clinical diagnosis and four with progression toward chronic kidney disease (CKD) (three required kidney replacement therapy at 25, 45 and 53 years and one had CKD Stage 2 at 46 years). Extrarenal involvement was observed in 24.5% of patients. Hematuria was transmitted in consecutive generations, while CKD was reported in nonconsecutive generations of 11 families [median age 53 years (range 16–80)]. Seventeen patients (32%) underwent kidney biopsy: findings were consistent with Alport syndrome in 12 cases and with thin basement membrane nephropathy in 5 cases. Conclusions Despite the benign course for these patients described in the literature, a significant percentage is at risk for disease progression. Consequently, we suggest that the assessment of these patients must take into account family history, genetic analysis and pathologic findings. After comparison with the literature, our data suggest that a different definition for Alport syndrome must be considered.

Background Histological findings of kidney involvement have been rarely reported in pediatric patients with SARS-CoV-2 infection. Here, we describe clinical, laboratory, and histological findings of two pediatric cases with almost exclusive kidney involvement by SARS-CoV-2. Results A 10-year-old girl with IgA vasculitis nephritis underwent kidney biopsy, showing diffuse and segmental mesangial-proliferative glomerulonephritis, and steroid therapy was initiated. After the worsening of the clinical picture, including an atypical skin rash, she was diagnosed with SARS-CoV-2. The re-evaluation of initial biopsy showed cytoplasmatic blebs and virus-like particles in tubular cells at electron microscopy. Despite SARS-CoV-2 clearance and the intensification of immunosuppression, no improvement was observed. A second kidney biopsy showed a crescentic glomerulonephritis with sclerosis, while virus-like particles were no longer evident. The second patient was a 12-year-old girl with a 3-week history of weakness and weight loss. Rhinitis was reported the month before. No medications were being taken. Blood and urine analysis revealed elevated serum creatinine, hypouricemia, low molecular weight proteinuria, and glycosuria. A high SARS-CoV-2-IgG titre was detected. Kidney biopsy showed acute tubular-interstitial nephritis. Steroid therapy was started with a complete resolution of kidney involvement. Conclusion We can speculate that in both cases SARS-CoV-2 played a major role as inflammatory trigger of the kidney damage. Therefore, we suggest investigating the potential kidney damage by SARS-CoV-2 in children. Moreover, SARS-CoV-2 can be included among infectious agents responsible for pediatric acute tubular interstitial nephritis.

Coronavirus disease 2019 (COVID-19) rapidly spread from China as a pandemic, with Italy one of the most affected countries worldwide. Unlike adults, children have a milder presentation of COVID-19, even when affected by CKD or on immunosuppressive therapy for glomerulopathies and kidney

Autosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene, encoding fibrocystin (FC), a large transmembrane protein of incompletely understood cellular function. Here, we show that a C‐terminal fragment of human FC can suppress a signalling module of the kinase SRC and signal transducer and activator of transcription 3 (STAT3). Consistently, we identified truncating genetic variants specifically affecting the cytoplasmic tail in ARPKD patients, found SRC and the cytoplasmic tail of fibrocystin in a joint dynamic protein complex and observed increased activation of both SRC and STAT3 in cyst‐lining renal epithelial cells of ARPKD patients.

© 2022 International Society of NephrologyIntroduction: Autosomal recessive polycystic kidney disease (ARPKD) is a rare monogenic disorder characterized by early onset fibrocystic hepatorenal changes. Previous reports have documented pronounced phenotypic variability even among siblings in terms of patient survival. The underlying causes for this clinical variability are incompletely understood. Methods: We present the longitudinal clinical courses of 35 sibling pairs included in the ARPKD registry study ARegPKD, encompassing data on primary manifestation, prenatal and perinatal findings, genetic testing, and family history, including kidney function, liver involvement, and radiological findings. Results: We identified 70 siblings from 35 families with a median age of 0.7 (interquartile range 0.1–6.0) years at initial diagnosis and a median follow-up time of 3.5 (0.2–6.2) years. Data on PKHD1 variants were available for 37 patients from 21 families. There were 8 patients from 7 families who required kidney replacement therapy (KRT) during follow-up. For 44 patients from 26 families, antihypertensive therapy was documented. Furthermore, 37 patients from 24 families had signs of portal hypertension with 9 patients from 6 families having substantial hepatic complications. Interestingly, pronounced variability in the clinical course of functional kidney disease was documented in only 3 sibling pairs. In 17 of 20 families of our cohort of neonatal survivors, siblings had only minor differences of kidney function at a comparable age. Conclusion: In patients surviving the neonatal period, our longitudinal follow-up of 70 ARPKD siblings from 35 families revealed comparable clinical courses of kidney and liver diseases in most families. The data suggest a strong impact of the underlying genotype.

Background: The goal of the treatment of Alport syndrome (AS) is to delay the progression of kidney damage. The current standard of care is the use of Renin Angiotensin Aldosterone System (RAAS) blockers: angiotensin-converting enzyme inhibition (ACEi), angiotensin receptor blockade, and, recently, spironolactone (SP). Aim of the study: the purpose of this retrospective study is to evaluate the efficacy (reduction of proteinuria and changes of glomerular function) and safety of a sequential introduction of RAAS blockers up to a triple RAAS blockade in pediatric proteinuric patients with AS. Methods: in this retrospective study (1995 to 2019), we evaluated proteinuria values in AS patients, during the 12 months following the beginning of a new RAAS blocker, up to a triple blockade. ACEi was always the first line of treatment, then ARB and SP were sequentially added if uPCR increased by 50% from the basal level in 2 consecutive samples during a 3-months observation period, or when uPCR ratio was &gt, 2 mg/mg. Results: 26 patients (mean age at treatment onset was 10.55 ± 5.02 years) were enrolled. All patients were on ACEi, 14/26 were started on a second drug (6/14 ARB, 8/14 SP) after a mean time of 2.2 ± 1.7 years, 7/26 were on triple RAAS blockade after a further period of 5.5 ± 2.3 years from the introduction of a second drug. Repeated Measure Anova analysis of log-transformed data shows that the reduction of uPCR values after Time 0 from the introduction of the first, second and third drug is highly significant in all three cases (p values = 0.0016, 0.003, and 0.014, respectively). No significant changes in eGFR were recorded in any group, apart from a 15-year-old boy with X-linked AS, who developed kidney failure. One patient developed mild hyperkaliemia, and one gynecomastia and symptomatic hypotension. No life-threatening events were recorded. Conclusions: double and triple RAAS blockade is an effective and safe strategy to reduce proteinuria in children with AS. Nevertheless, we suggest monitoring eGFR and Kaliemia during follow-up.

Infections are a major concern in children on KRT and with CKD. Risk factors include immunosuppression, multiple contacts in dialysis units, and hospital visits ([1][1]). Italy was one of the countries most affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak ([2][2

An Italian 13-year-old boy immunosuppressed due to kidney transplant presented in November 2018 with acute flaccid paralysis with anterior horn cell involvement resembling the clinical, radiological, and laboratory features of poliomyelitis. Enterovirus was molecularly identified in cerebral spinal fluid and stool samples and the sequence analysis of the VP1 gene of enterovirus genome revealed the presence of Echovirus 30 both in CSF and in stool samples. Echovirus 30 is an emerging neurotropic virus able to cause outbreaks of aseptic meningitis and meningoencephalitis all over the world, but acute flaccid paralysis is not a classical manifestation. A 6-month follow-up revealed a poor outcome with severe motor deficits and only slight improvement in disability. Clinicians must be aware of the possible role of Echovirus 30 in acute flaccid paralysis and active surveillance should consider the possible influence of immunosuppression on the symptoms caused by the widening spectrum of enterovirus infections.

Objective We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. Methods Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. Results The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03–0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002–0.000001). Conclusion The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Autosomal recessive polycystic kidney disease (ARPKD) is a severe disease of early childhood that is clinically characterized by fibrocystic changes of the kidneys and the liver. The main cause of ARPKD are variants in the PKHD1 gene encoding the large transmembrane protein fibrocystin. The mechanisms underlying the observed clinical heterogeneity in ARPKD remain incompletely understood, partly due to the fact that genotype-phenotype correlations have been limited to the association of biallelic null variants in PKHD1 with the most severe phenotypes. In this observational study we analyzed a deep clinical dataset of 304 patients with ARPKD from two independent cohorts and identified novel genotype-phenotype correlations during childhood and adolescence. Biallelic null variants frequently show severe courses. Additionally, our data suggest that the affected region in PKHD1 is important in determining the phenotype. Patients with two missense variants affecting amino acids 709-1837 of fibrocystin or a missense variant in this region and a null variant less frequently developed chronic kidney failure, and patients with missense variants affecting amino acids 1838-2624 showed better hepatic outcome. Variants affecting amino acids 2625-4074 of fibrocystin were associated with poorer hepatic outcome. Thus, our data expand the understanding of genotype-phenotype correlations in pediatric ARPKD patients and can lay the foundation for more precise and personalized counselling and treatment approaches. German Society for Pediatric Nephrology (GPN); ESCAPE Network; European Society for Paediatric Nephrology (ESPN); German PKD foundation; Koeln Fortune program; GEROK program of the Medical Faculty of University of Cologne; Marga and Walter Boll-Foundation; German Federal Ministry of Research and Education (BMBF)Federal Ministry of Education & Research (BMBF) [01GM1515, 01GM1903]; working group CAKUT of the ESPN; working group Inherited Kidney Diseases of the ESPN We thank the German Society for Pediatric Nephrology (GPN) and the ESCAPE Network for their support. We thank Mr Mathias Burgmaier (Aachen) and Mr Samuel Kilian (Heidelberg) for support in conducting statistical analysis. ML was supported by grants of the GPN, the European Society for Paediatric Nephrology (ESPN), the German PKD foundation, the Koeln Fortune program, the GEROK program of the Medical Faculty of University of Cologne, and the Marga and Walter Boll-Foundation. FS, CB, and ML are supported by the German Federal Ministry of Research and Education (BMBF grant 01GM1515 and 01GM1903). KB was supported by the Koeln Fortune program and the GEROK program of the Medical Faculty of University of Cologne, as well as the Marga and Walter Boll-Foundation. This work was generated within the European Reference Network for Rare Kidney Disorders (ERKNet). The work was supported by the working groups CAKUT and Inherited Kidney Diseases of the ESPN.

Objective To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). Study design International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. Results Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. Conclusions The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.

The kidney is often the target of immune system dysregulation in the context of primary or systemic disease. In particular, the glomerulus represents the anatomical entity most frequently involved, generally as the expression of inflammatory cell invasion or circulant or in situ immune-complex deposition. Glomerulonephritis is the most common clinical and pathological manifestation of this involvement. There are no universally accepted classifications for glomerulonephritis. However, recent advances in our understanding of the pathophysiological mechanisms suggest the assessment of immunological features, biomarkers, and genetic analysis. At the same time, more accurate and targeted therapies have been developed. Data on pediatric glomerulonephritis are scarce and often derived from adult studies. In this review, we update the current understanding of the etiologic events and genetic factors involved in the pathogenesis of pediatric immunologically mediated primitive forms of glomerulonephritis, together with the clinical spectrum and prognosis. Possible new therapeutic targets are also briefly discussed.

A Multisite copolymer with functionalizable units inserted at precise locations was synthesised by one-pot Reversible Addition–Fragmentation Chain-Transfer (RAFT) polymerization and sequential Single Monomer Unit Insertion (SMUI) and Chain Extension (ChainExt) using Styrene (Sty) and Maleic Anhydride (MAnh) as comonomers. The multisite copolymer was based on a polystyrene (PSty) backbone (ca. 5700 g mol−1) with MAnh units inserted locally at four positions in the backbone. First, a well-defined macroCTA (1400 g mol−1 – Đ = 1.07) was synthesised by optimized RAFT polymerization (high conversion, high livingness and low dispersity) of styrene (DP = 10) using industrial grade butyl-2-methyl-2-[(dodecylsulfanylthiocarbonyl)sulfanyl] propionate as chain transfer agent (CTA-Ester – 80% pure). Subsequently, the polystyrene macroCTA was used for one-pot SMUI using a small excess of MAnh monomer (DPtarget = 1.5). The copolymer was chain extended by styrene leading to a polystyrene backbone with MAnh units (1.5 in average) located in the middle of the chain. By repeating SMUI and ChainExt, several units of MAnh were inserted locally along the polystyrene backbone (every 10 units on average) to give a functionalizable multisite copolymer (Đ = 1.35). Long alkyl chains (stearyl) were added by esterification of maleic anhydride moieties to obtain branched architecture.

Poly(2-acrylamido-2-methylpropane sulfonic acid) is a polyelectrolyte currently used in numerous industrial applications. Herein, we report the use of reversible addition fragmentation chain transfer (RAFT) polymerization to prepare a range of well-defined homopolymers and block copolymers of 2-acrylamido-2-methylpropane sulfonic acid (AMPS®) and either N-hydroxyethyl acrylamide (HEAm) or 4-acryloylmorpholine (NAM) as a comonomer. We also describe the one-pot synthesis of multiblock core cross-linked star copolymers of AMPS® and HEAm with low dispersities (

BackgroundHenoch-Schönlein Purpura (HSP) is the most common vasculitis of childhood and affects the small blood vessels. Pulmonary involvement is a rare complication of HSP and diffuse alveolar hemorrhage (DAH) is the most frequent clinical presentation. Little is known about the real incidence of lung involvement during HSP in the pediatric age and about its diagnosis, management and outcome.MethodsIn order to discuss the main clinical findings and the diagnosis and management of lung involvement in children with HSP, we performed a review of the literature of the last 40 years.ResultsWe identified 23 pediatric cases of HSP with lung involvement. DAH was the most frequent clinical presentation of the disease. Although it can be identified by chest x-ray (CXR), bronchoalveolar lavage (BAL) is the gold standard for diagnosis. Pulse methylprednisolone is the first-line of therapy in children with DAH. An immunosuppressive regimen consisting of cyclophosphamide or azathioprine plus corticosteroids is required when respiratory failure occurs. Four of the twenty-three patients died, while 18 children had a resolution of the pulmonary involvement.ConclusionsDAH is a life-threatening complication of HSP. Prompt diagnosis and adequate treatment are essential in order to achieve the best outcome.

Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes. Despite simultaneous screening of these genes being widely available, mutation detection still remains incomplete in a non-marginal portion of patients. Here, we applied whole-exome sequencing (WES) in 3 Italian families negative after candidate-gene analyses. In Family 1, we identified a novel heterozygous intronic variant (c.2245-40A>G) -outside the conventionally screened candidate region for diagnosis- potentially disrupting COL4A5 exon29 splicing. Using a minigene-based approach in HEK293 cells we demonstrated that this variant abolishes exon29 branch site, causing exon skipping. Moreover, skewed X-inactivation of the c.2245-40A>G allele correlated with disease severity in heterozygous females. In Family 2, WES highlighted a novel COL4A5 hemizygous missense mutation (p.Gly491Asp), which segregates with the phenotype and impacts on a highly-conserved residue. Finally, in Family 3, we detected a homozygous 24-bp in-frame deletion in COL4A3 exon1 (NM_000091.4:c.30_53del:p.Val11_Leu18del or c.40_63del24:p.Leu14_Leu21del), which is ambiguously annotated in databases, although it corresponds to a recurrent AS mutation. Functional analyses showed that this deletion disrupts COL4A3 signal peptide, possibly altering protein secretion. In conclusion, WES -together with functional studies- was fundamental for molecular diagnosis in 3 AS families, highlighting pathogenic variants that escaped previous screenings.

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.

Objectives:Percutaneous transluminal renal angioplasty (PTRA) without stenting is the recommended treatment for hypertensive children with renal artery stenosis (RAS). Not infrequently RAS is resistant to PTRA or recurs after the procedure. To circumvent PTRA limitations percutaneous cutting balloon

We have investigated how four different pour point depressant (PPD) polymers affect the pour point transition in mixtures of a single pure wax in a solvent. We used either n-eicosane (C20), CH3(CH2)18CH3, n-tetracosane (C24), CH3(CH2)22CH3 or n-hexatriacontane (C36), CH3(CH2)34CH3 as the wax component with either n-heptane or toluene as the solvent component. For all wax–solvent combinations, the measured variation of wax solubility with temperature is well predicted by ideal solution theory. The variation of pour point temperature as a function of the overall wax concentration is quantitatively modelled using the idea that, for each overall wax concentration, the pour point occurs at a temperature at which a critical volume fraction ϕ* of wax crystals has precipitated. Close to the pour point temperature, extraction and examination of the wax crystals show they consist of polydisperse, irregularly-shaped platelets with axial ratios (h/d, where h is the plate thickness and d is the plate long dimension) in the range 0.005–0.05. It is found that the measured ϕ* values corresponding to the pour point transitions are weakly correlated with the wax crystal axial ratios (h/d) for all wax–solvent–PPD polymer combinations. These results indicate that the pour point transition occurs at a volume fraction larger than the value at which the volumes of rotation of the platelet crystals overlap, i.e., 2.5(h/d) < ϕ* < 11(h/d). PPD polymers work, in part, by increasing the wax crystal axial ratio (h/d), thereby increasing ϕ* and reducing the pour point temperature. Since the PPD's ability to modify the wax crystal shape relies on its adsorption to the crystal-solution surface, it is anticipated and observed experimentally that optimum PPD efficacy is correlated with the difference between the wax and the polymer solubility boundary temperatures. This finding and the mechanistic insight gained here provide the basis for a simple and rapid screening test to identify candidate species likely to be effective PPDs for particular wax systems.

Immunoglobulin A (IgA) nephropathy is considered to be the commonest primary glomerulonephritis worldwide. The commonest clinical presentation of the disease is macroscopic hematuria, and nephrotic syndrome (NS) at the time of onset of symptoms is a predictor of poor outcome in both adults and children. In this report we describe a case of IgA nephropathy in a 15-year-old girl with a diagnosis of NS who was admitted to our hospital following 15 days of remarkable weight gain, and eyelid and pretibial oedema. NS was diagnosed when she was 3 years old. During the period between diagnosis and our observation the patient presented with three episodes of relapse. After the third episode a renal biopsy was performed and, together with clinical data, this enabled us to make the diagnosis of IgA nephropathy. NS is now recognized as a possible clinical manifestation of an IgA nephropathy, even at onset. Based on this case report, we suggest that a more vigilant management of children with NS may be necessary, even if they do not have atypical characteristics at onset. We suggest that it may be better to perform a renal biopsy at the time of first relapse.

Henoch-Schönlein purpura (HSP), the commonest vasculitis in children, occurs most frequently between the ages of 4 and 6 years. We report the case of a 3-year-old boy with an otomastoiditis who was treated with cephalosporin and corticosteroids following a typical purpuric skin rash diagnosed as HSP. The patient also developed an acute occurrence of impairment of the glans, prepuce and penis 4 days after recovery that completely disappeared after a further 2 days, with the cutaneous rash subsiding on discharge from hospital.

Protein-energy wasting (PEW) is defined as a state of decreased body protein mass and fuel reserves (body protein and fat mass) and is a common complication of chronic kidney disease (CKD). It is multifactorial: the main causative factors are hormonal imbalances and a low nutrient intake, but low residual renal function, inadequate dialysis dose, chronic inflammation and metabolic acidosis are other important contributory factors. Adult PEW has been defined, but there is no accepted definition of pediatric PEW and consequently no precise diagnostic criteria. Assessing nutritional status in children is also complicated by the absence of a gold standard, specific abnormalities in body composition, and the slowly progressive course of the disease. The evaluation of PEW should take into account all of its pathogenetic aspects, which include dietary assessment, clinical and anthropometric assessment (based on weight, height, and body mass index), a panel of biochemical parameters, and a normalized protein catabolic rate (in the case of adolescents on hemodialysis). Bioimpedance indices can be used in individual patients on a regular basis in centers with expertise. The longitudinal follow-up data relating to the above parameters are valuable for comparing patient and normative data. Given the complex nature of PEW, only a multidisciplinary approach can provide an accurate assessment of nutritional status and its derangements in children with CKD and on dialysis.

1.Pediatric Clinic 2, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ospedale C a Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 2.Pediatric Emergency Unit, Fondazione IRCCS C a Granda Ospedale Maggiore Policlinico, Milan, Italy 3.Pediatric Intensive Care Unit, Department of Anesthesia, Intensive Care and Emergency, Fondazione IRCCS C a Granda Ospedale Maggiore Policlinico, Milan, Italy 4.Pediatric Nephrology Unit, Fondazione IRCCS C a Granda Ospedale Maggiore Policlinico, Milan, Italy 5.Cystic Fibrosis Center, Fondazione IRCCS C a Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy 6.International Center for the Assessment of Nutritional Status DiSTAM, University of Milan, Milan, Italy 7.Clinical Epidemiology Unit, Liver Research Center, Basovizza and Fondazione IRCCS C a Granda, Ospedale Maggiore Policlinico, Milan, Italy

Sirs,The article by Hobbs and coworkers [1] provides scientificevidence for what we believe is a common clinical practice:the use of rasburicase in hyperuricemic newborns withacute kidney injury (AKI).These authors retrospectively reviewed the charts of 7hyperuricemic infants with AKI, successfully treated with asingle dose of rasburicase (0.17±0.04 mg/kg).Duringthelastfewyearswealsoexperiencedtheefficacyand safety of rasburicase in 10 AKI newborns (7 boys, 3girls), with a mean (± SD) body weight of 1,226 g (± 644.4),born at 29.4 weeks (± 30 days) and with a mean age atadministration of therapy of 20.2 days (± 11.5). Six of themwere of very low birth weight (VLBW) and 9 werepremature (data not published).After a single intravenous dose of rasburicase (0.2 mg/kgin 30 min) we also observed a statistically significantdecrease in serum uric acid concentration of a mean levelranging from 14.5±3.6 mg/dl to 6.6±7.5 mg/dl (p

Abnormalities of nutrition status are a common problem in children on peritoneal dialysis (PD) and a source of significant morbidity and mortality. The state of decreased body protein mass and fuel reserves (body protein and fat mass) common in PD patients is now better known as protein–energy wasting (PEW). Protein–energy wasting is a slow, progressive process in chronic kidney disease. The correct approach to this problem includes measurement of early, intermediate, and late markers of PEW, and consideration of the risk factors specific to the patient and to PD. The earliest markers of PEW are associated with some symptoms observed clinically: a decrease in dietary intake and an increase in inflammatory markers. The second stage in the development of PEW (patients with established PEW) is characterized by abnormalities in numerous markers: bioimpedance analysis (BIA) and anthropometric indices, other indices of body mass and composition, biochemical parameters, and indices of protein, glucose, and lipid metabolism. When PEW is established, clear clinical signs become evident: patients in this stage are characterized by high rates of hospitalization and an increased risk for morbidity and mortality as compared with patients without cachexia. Risk factors for PEW can already be present in an apparently well-nourished child who initiates PD: glucose absorption from PD fluid, abdominal distension from PD volume, gastroesophageal reflux, and even more importantly, inadequate dialysis dose in relation to decline in residual renal function. Given the complexity of the pathogenesis and clinical picture of PEW, no single measure, but rather panels of nutritional measures are necessary to diagnose the condition. Combined nutrition scores such as the anthropometry–BIA nutrition score may add value to the monitoring of nutrition status in children on PD.

Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.

The aim of this trial was to compare the safety and efficacy of homotoxicological remedies versus placebo and versus desmopressin (dDAVP) in the treatment of monosymptomatic nocturnal enuresis (MNE). We conducted a randomised, double-blind, double-dummy, controlled trial in which 151 children with MNE were randomly assigned to receive oral homotoxicological remedies (n = 50), dDAVP (n = 50) or placebo (n = 51). The primary outcomes were: the reduction of wet nights per week after 3 months of therapy; the evaluation of the numbers and percentages of non-responders and responders; the number of children relapsing after initial response and the number of children attaining 14 consecutive dry nights during the treatment. The secondary outcome was the detection of adverse effects. Baseline clinical characteristics were similar in the three groups of patients. After the 3 months of therapy there was a significant difference between the three groups (P < 0.001) in the mean number of wet nights per week. The daily dose of dDAVP produced a statistically significant decrease (62.9%) in wet nights compared to placebo (2.4%) (P < 0.001) and compared to homotoxicological remedies (30.0%) (P < 0.001). There was a significant decrease in wet nights among the group treated with homotoxicological medications if compared with placebo (P < 0.001). The full response achieved with homotoxicological remedies (20%) was superior if compared with placebo (0%) (P < 0.001). Homotoxicology was superior to placebo (P < 0.001) with regard to the number of children attaining 14 consecutive dry nights during treatment. Our study demonstrates that homotoxicology is safe and effective when compared with placebo, even if it is significantly less effective than dDAVP in this clinical condition.

Objective. To analyse the urinary excretion of glycosaminoglycans (GAGs) in patients with either urinary incontinence or nocturnal enuresis. Material and methods. The study population comprised 65 patients with either nocturnal enuresis (n=34) or urinary incontinence (n=31) and 67 controls. Excretion of urinary GAGs was assessed using the sodium tetraborate–carbazole method. Results. GAG excretion in patients with urinary incontinence was significantly higher than that in controls (p

The purpose of the study was to evaluate the health care of children living with their mothers in prison. No previous studies on this topic have been conducted in Italy. Italian law allows female prisoners to keep their babies with them until the age of 3 years in specific nest areas. Currently, there are 15 nest areas in Italian prisons, 2804 female inmates, 64 prisoners with children aged

The interplay between side-chain and main-chain conformations is a distinctive characteristic of proline residues. Here we report the results of a statistical analysis of proline conformations using a large protein database. In particular, we found that proline residues with the preceding peptide bond in the cis state preferentially adopt a down puckering. Indeed, out of 178 cis proline residues, as many as 145 (81%) are down. By analyzing the 1-4 and 1-5 nonbonding distances between backbone atoms, we provide a structural explanation for the observed trend. The observed correlation between proline puckering and peptide bond conformation suggests a new mechanism to explain the reported shift of the cis-trans equilibrium in proline derivatives. The implications of these results for the current models of collagen stability are also discussed.