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Objective: To determine whether mucocutaneous manifestations are associated with major organ involvement in a UK national cohort of juvenile-onset SLE (JSLE) patients., Methods: JSLE patients (n = 241) from 15 different centres whose diagnosis fulfilled four or more of the ACR criteria were divided into two groups: those with at least one ACR mucocutaneous criterion (ACR skin feature positive) and those without (ACR skin feature negative) at diagnosis. The relative frequency of skin involvement was described by the paediatric adaptation of the 2004 British Isles Lupus Assessment Group (pBILAG-2004) index., Results: One hundred and seventy-nine patients (74%) had ACR-defined skin involvement with no significant demographic differences compared with those without. ACR skin feature negative patients showed greater haematological (84% vs 67%), renal (43% vs 26%) (P < 0.05) and neurological (16% vs 4%) involvement (P = 0.001). Forty-two per cent of ACR skin feature negative patients had skin involvement using pBILAG-2004, which included maculopapular rash (17%), non-scaring alopecia (15%), cutaneous vasculitis (12%) and RP (12%). ACR skin feature negative patients with moderate to severe skin involvement by pBILAG-2004 showed greater renal and haematological involvement at diagnosis and over the follow-up period (P < 0.05). Higher immunosuppressive drug use in the skin feature negative group was demonstrated., Conclusion: Patients who fulfil the ACR criteria but without any of the mucocutaneous criteria at diagnosis have an increased risk of major organ involvement. The pBILAG-2004 index has shown that other skin lesions may go undetected using the ACR criteria alone, and these lesions show a strong correlation with disease severity and major organ involvement., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting., Methods: Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity., Results: JSLE patients (n = 64; median age 14.1 years) were seen at 3 (interquartile range: 2-5) clinical reviews over 364 (182-532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p < 0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p = 0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p = 0.04) over time., Conclusion: Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients.

Background: C1q nephropathy has been suggested as a separate disease entity. C1q positivity has also been described in association with nephrotic syndrome (NS) as a potential marker for worse outcome. The aims of this study were to describe the clinical characteristics, laboratory parameters and outcomes of 35 children whose renal histology revealed predominant mesangial C1q deposition and to investigate if the experience at our institution supports the above hypothesis., Method: Clinical and pathological characteristics of all children whose kidney biopsies showed positive C1q staining were retrospectively recorded. The outcome of children with minimal change nephrotic syndrome (MCNS) and predominant mesangial C1q deposition based on C1q staining was compared with that of a concurrent group of children with MCNS with no such immune staining., Results: The median age of the patient cohort was 4.5 years (range 6 months to 16 years), 69 % were boys and 88 % presented with nephrotic syndrome (NS). Children with C1q staining and MCNS had more relapses (p = 0.001) and shorter relapse-free periods (p = 0.033) than those with negative immunostaining, but the long-term outcomes were similar in both groups., Conclusion: Our data do not support C1q nephropathy as a separate diagnostic category. Children with MCNS and mesangial C1q deposition (staining) showed more relapses but no difference in long term renal outcome.

Controversy and lack of consensus have been encountered in the management of pediatric urinary tract infection (UTI), including its diagnosis, radiological investigations and the use of antibiotic therapy. In this review, we discuss the need for radiological investigations and the extent of their use as well as the need for prophylactic antibiotics in children with UTI and vesicoureteral reflux. Only a small proportion of children with first UTI and no history of antenatal renal abnormalities have clinically important malformations. Renal ultrasound should be performed in febrile infants and young children with UTI; a micturating cystourethrogram should not be performed routinely after the first febrile UTI. Long-term antibiotics appear to reduce the risk of recurrent symptomatic UTI in susceptible children, although the clinical benefit is marginal. Current recommendations encourage performing radiological investigations only in children at risk and discourage routine prophylactic antibiotic use.

Objective: Polyarteritis nodosa (PAN) is a rare disease of childhood. The aims of this study were to describe the clinical features, treatment, and outcome of systemic childhood PAN and to identify predictors of relapse., Methods: A single-center retrospective medical records review of children with PAN fulfilling the European League Against Rheumatism (EULAR)/Paediatric Rheumatology European Society (PRES)/Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria who were seen over a 32-year period was performed. Data on demographic and clinical features, treatments, relapses (recurrence of clinical signs/symptoms or occurrence of new symptoms after initial remission requiring escalation or resumption of immunosuppressive therapy), and deaths were recorded. A disease activity score was retrospectively assigned using the Paediatric Vasculitis Activity Score (PVAS) instrument. Cox regression analysis was used to identify significant predictors of relapse., Results: Sixty-nine children with PAN were identified; 55% were male, and their median age was 8.5 years (range 0.9-15.8 years). Their clinical features at presentation were fever (87%), myalgia (83%), skin (88%), renal (19%), severe gastrointestinal (GI) (10%), and neurologic (10%) involvement. The PVAS at presentation was 9 of 63 (range 4-24). Histopathologic analysis of the skin showed necrotizing vasculitis in biopsy samples from 40 of 50 children. Results of selective visceral arteriography suggested the presence of PAN in 96% of patients. Treatment included cyclophosphamide and corticosteroids (83%), plasma exchange (9%), and biologic agents (after 2002; 13%). The relapse rate was 35%, and the mortality rate was 4%. Severe GI involvement was associated with increased risk of relapse (P = 0.031), while longer time to induce remission (P = 0.022) and increased cumulative dose of cyclophosphamide (P = 0.005) were associated with lower relapse risk., Conclusion: Childhood PAN is a severe inflammatory disease of insidious onset and variable clinical presentation. Relapses occurred more frequently in those with severe GI involvement. A higher cumulative dose of cyclophosphamide was associated with a lower risk of relapse., (Copyright © 2013 by the American College of Rheumatology.)

Rituximab was initially developed for the treatment of patients with B cell lymphoma but has during the last decade proven to be quite effective in treating a range of kidney diseases including lupus nephritis, nephrotic syndrome, and also in different situations before and after a renal transplant. We will here review the scientific basis for the use of rituximab in children with renal diseases and give recommendations both regarding its clinical use and need for further research.

CME EDUCATIONAL OBJECTIVES: 1.Review recent guidelines for diagnosis and treatment of urinary tract infections in children younger than 2 years.2.Review recent recommendations for imaging children with urinary tract infection.3.Understand rationale for recent treatment recommendations and prophylaxis of children with urinary tract infection., (Copyright 2013, SLACK Incorporated.)

Renovascular hypertension (RVH) can be caused by many different diseases, with the most common being fibromuscular dysplasia (FMD) and Takayasu arteritis (TA). A strikingly different diagnostic pattern is seen in children with RVH from different parts of the world. In Europe and North America, these children are mainly diagnosed as having FMD while in Asia and South Africa they will most often get a diagnosis of TA. When comparing the clinical diagnosis for FMD and TA, it becomes obvious that there is a great deal of overlap between the definitions of these two conditions. Different ways to come to the most accurate diagnosis using imaging of the blood vessel wall and positron emission tomography (PET) will be discussed. How an accurate diagnosis should influence the treatment of the children with these conditions will also be addressed.

Although the epidemic of childhood obesity in the developed world has resulted in more children being diagnosed with primary hypertension, renovascular disease remains an important consideration. The reason for investigation is to try and delineate if renovascular disease is present, as there is the potential to treat this group of patients. Those patients are usually identified by poor blood pressure control, despite the use of multiple anti-hypertensive medications or having known associated syndromes. Although advances in Doppler renal ultrasonography, computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have occurred over the last decade, digital subtraction angiography remains the gold standard investigation, and offers a possible therapeutic intervention at the same time.

Background: Children with renovascular hypertension often present with severe hypertension. Some children have severe obstruction of their renal arteries resulting in <10% relative function on [(99m)Tc]dimercaptosuccinic acid (DMSA) scan. Conventional treatment of these children has been nephrectomy of the poorly functioning kidney to normalise their blood pressure (BP)., Case-Diagnosis/treatment: We describe three children aged 20 months to 9 years with severe renal artery stenosis and severe hypertension who had radionucleotide uptake of 0% in one kidney. In one case, no renal perfusion was demonstrated by duplex ultrasound scan. Significant recovery of relative renal function of 18 to 52% was achieved after revascularisation by percutaneous angioplasty or open surgery of the obstructed renal artery., Conclusion: These cases illustrate that scintigraphy alone cannot be used to predict salvageable function in children with renovascular disease.

Purpose: Sphingosine-1-phosphate (S1P) is an active sphingolipid with chemotactic abilities and has been linked to inflammatory mediators and autoimmune disease. The aim of this study was to assess whether children with juvenile-onset systemic lupus erythematosus (JSLE) express increased systemic and/or urinary concentrations of S1P., Methods: A subgroup of patients participating in the UK JSLE Cohort Study, were invited to participate. Cross sectional serum and urine samples were prospectively collected along with demographic and standard clinical data. Results were compared to a cohort of disease controls (Henoch Schonlein Purpura; HSP) and healthy controls (HC)., Results: The median age of JSLE patients (n = 15) was 13.6 years (7.2-16.9 years). The serum concentrations of S1P in JSLE patients (7.4 uM, IQR 6.3-12.3 uM) were statistically significantly increased when compared to patients with HSP (n = 10; 5.2 uM, IQR 4.0-7.9 uM; p = 0.016) and HCs (n = 10; 3.8 uM, IQR 2.1-5.8 uM; p = 0.003). There was a trend towards increased serum S1P concentrations between patients with active lupus nephritis (n = 8; 8.7 uM, IQR 6.2-15.3 uM) compared to lupus non-nephritis (n = 7; 6.6 uM, IQR 6.3-10.6 uM; p = 0.355). No relationship was found between disease activity markers and S1P. Urine S1P concentrations were no different between JSLE patients (56.0 nM, IQR 40.3-96.6 nM) and HCs (58.7 nM, IQR 0-241.9 nM; p = 0.889)., Conclusions: We have demonstrated, for the first time, an increased serum concentration of S1P in a cohort of JSLE patients. These findings highlight a role of S1P in the pathophysiology of JSLE that warrants further investigation.

Systemic lupus erythematosus (SLE) is a multifactorial disorder with multigenic inheritance and various environmental factors implicated in its aetiopathogenesis. Despite the multiple mechanisms involved in the aetiology of SLE being elusive, recent studies have made progress in our understanding of the pathogenic mechanisms via abnormal regulation of cell-mediated and humoral immunity that lead to tissue damage. The heterogeneity of the clinical manifestations probably reflects the complexity of the disease pathogenesis itself. The immune system in SLE is characterised by a complex interplay between overactive B cells, abnormally activated T cells and antigen-presenting cells. This interplay leads to the production of an array of inflammatory cytokines, apoptotic cells, diverse autoantibodies and immune complexes that in turn activate effector cells and the complement system, leading to tissue injury and damage which are the hallmarks of the clinical manifestations. SLE patients have dysregulation of inflammatory cytokines, chemokines and immune response-related genes, as well as of the genes involved in apoptosis, signal transduction and the cell cycle.

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in infants and children. Lower UTI is the most commonly presenting and in the majority of cases can be easily treated with a course of antibiotic therapy with no further complications. A number of antimicrobials have been used to treat children with lower UTIs; however is it unclear what are the specific benefits and harms of such treatments., Objectives: This review aims to summarise the benefits and harms of antibiotics for treating lower UTI in children., Search Methods: We searched the Renal Group's Specialised Register (April 2012), CENTRAL (The Cochrane Library 2012, Issue 5), MEDLINE OVID SP (from 1966), and EMBASE OVID SP (from 1988) without language restriction. Date of last search: May 2012., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs in which antibiotic therapy was used to treat bacteriologically proven, symptomatic, lower UTI in children aged zero to 18 years in primary and community healthcare settings were included., Data Collection and Analysis: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratios (RR) with 95% confidence intervals (CI)., Main Results: Sixteen RCTs, analysing 1,116 children were included. Conventional 10-day antibiotic treatment significantly increased the number of children free of persistent bacteriuria compared to single-dose therapy (6 studies, 228 children: RR 2.01, 95%CI 1.06 to 3.80). No heterogeneity was observed. Persistent bacteriuria at the end of treatment was reported in 24% of children receiving single-dose therapy compared to 10% of children who were randomised to 10-day therapy. There were no significant differences between groups for persistent symptoms, recurrence following treatment, or re-infection following treatment. There was insufficient data to analyse the effect of antibiotics on renal parenchymal damage, compliance, development of resistant organisms or adverse events. Despite the inclusion of 16 RCTs, methodological weakness and small sample sizes made it difficult to conclude if any of the included antibiotics or regimens were superior to another., Authors' Conclusions: Although antibiotic treatment is effective for children with UTI, there are insufficient data to answer the question of which type of antibiotic or which duration is most effective to treat symptomatic lower UTI. This review found that 10-day antibiotic treatment is more likely to eliminate bacteria from the urine than single-dose treatments. No differences were observed for persistent bacteriuria, recurrence or re-infection between short and long-course antibiotics where the antibiotic differed between groups. This data adds to an existing Cochrane review comparing short and long-course treatment of the same antibiotic who also reported no evidence of difference between short and long-course antibiotics.

Objective: The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort., Methods: Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE., Results: Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1., Conclusion: The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen., (Copyright © 2012 by the American College of Rheumatology.)

A large number of new studies on the treatment of systemic lupus erythematosus (SLE) have recently been or are about to be published. Unfortunately, all these studies have been performed in adult patients and there are no studies in children. There is, however, a strong need for more effective drugs with, if possible, fewer side-effects also in children. We do thus need to carefully asses the studies in adult patients to evaluate which of the new drugs can be tried in children with severe lupus nephritis. Some of the new studies have been largely confirmatory, such as demonstrating the efficacy of mycophenolate mofetil in the treatment of SLE, but others have been surprising, such as the lack of efficacy of rituximab. The debate as to why the rituximab studies got negative results is ongoing. Lastly, there is an emergence of novel medications for the treatment of SLE, mostly monoclonal antibodies targeting various aspects of the immune system: belimumab, an antibody affecting B-cell function, is likely to become the first new drug registered for lupus for many years as several large randomized studies have shown significant (albeit not dramatic) responses to this antibody. Many other drugs are in the pipeline and will hopefully come to the clinical arena. This review aims to give a critical appraisal of the plethora of studies in the context of the clinical reality of a pediatric nephrologist treating patients with SLE.

A higher proportion of patients with juvenile-onset systemic lupus erythematosus (JSLE) will have renal involvement compared with adult-onset disease, some progressing to renal failure in adulthood. Histological examination is the gold standard for diagnosing lupus nephritis (LN), but its invasive nature limits routine use. Using cross-sectional cohort analysis, we aimed to determine whether urinary concentrations of monocyte chemoattractant protein-1 (MCP1), alpha-1-acid glycoprotein (AGP) and interferon-inducible protein 10 (IP10) are biomarkers of active LN. Sixty JSLE patients recruited to the UK JSLE Cohort Study were categorized according to the British Isles Lupus Assessment Group (BILAG) activity index. Patients with active renal JSLE (n = 8; renal BILAG score A, B) had significantly higher urinary MCP1 concentrations than patients with inactive renal disease (n = 52; renal BILAG score C, D, E; 582 pg/mg creatinine [Cr], 207 pg/mg Cr; p = 0.018) or healthy controls (n = 23; 117 pg/mg Cr; p = 0.005). Urinary AGP concentration was significantly elevated in patients with active renal disease compared with inactive renal disease (1517 ng/mg Cr, 485 ng/mg Cr; p = 0.027) or healthy controls (313 ng/mg Cr; p = 0.013). Urinary IP10 concentration was not significantly different between groups, but did strongly correlate with uMCP and uAGP levels (rho = 0.38, p = 0.009; rho = 0.33, p = 0.021). Urinary MCP1 and AGP are biomarkers of LN, providing insight into its pathophysiology. Longitudinal studies are warranted.

Aims: Paediatric guidance on diagnosis and treatment of urinary tract infections (UTIs) has in the past largely focused on identifying children with vesicoureteral reflux, thought to be at greatest risk of renal scarring. This practice has been questioned, specifically the accepted association between UTI and end-stage renal failure (ESRF) through renal scarring. The aim of this article is to ascertain whether we can predict with confidence the true level of risk that a child with a first-time UTI will subsequently develop ESRF attributable to UTI., Methods: Using data available from renal registries, an analytical approach based on previous estimates of risk is used to demonstrate the range of plausible estimates of risk that can be generated and levels of uncertainty that surrounds those estimates., Results: Estimates of the perceived risk of developing ESRF following UTI range from 1/154 to 1/199,900 and are heavily dependent on the assumptions made and the source of data., Conclusion: There is considerable uncertainty in the relationship between childhood UTI and risk of ESRF based on the data currently available. Until further evidence is available, clinicians will continue to debate the risk of UTI and ESRF and consensus opinion will continue to guide management., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Dyslipidemia has been shown to be a risk factor for increased cardiovascular morbidity and mortality in adult patients with chronic kidney disease (CKD) stages 2-4. In patients on dialysis, a paradoxical correlation has been found between low cholesterol values and increased mortality rates. No data exist in children. Treatment with statins has been convincingly shown to both reduce blood lipid levels and mortality rates from cardiovascular disease in adult patients in CKD stages 2-4. There is no strong literature support for treating patients on dialysis or after having had a transplant. Data on benefits of statin therapy do not exist in children with CKD. There are many differences between adult and paediatric kidney patients, and I caution on extrapolating the findings in adult patients to children. Studies are thus needed to evaluate the benefits and potential problems of statin treatment in children with CKD.

Mid aortic syndrome (MAS) is a rare condition often presenting with severe hypertension. It is characterized by narrowing of the abdominal aorta. We here describe a case of complete occlusion of the abdominal aorta presenting in infancy. This child presented at four months of age with heart failure and hypertension. CT angiogram showed total narrowing of the abdominal aorta. This was initially felt to be too severe for surgical treatment and he was planned for palliative care. We were however able to improve his blood pressure with antihypertensive agents and he underwent succesful angioplasty at five and a half months of age. He has required three further angioplasty procedures and still needs two antihypertensive agents to control his blood pressure. His renal function remains normal and at age six years he has excellent quality of life with normal growth and development. This case illustrates that the combination of medical treatment and angioplasty can give an excellent long-term treatment response even in children with extremely severe MAS. This boy now has normal blood pressure and has experienced normal growth, development and quality of life.

Renal fibromuscular dysplasia (FMD) can cause hypertension, and previous reports suggest that FMD is familial. We hypothesized that, in families containing an individual with proven FMD, relatives of index cases would have an increased risk of hypertension. ACTA2 mutations cause a spectrum of extra-renal arteriopathy, leading to our second hypothesis that mutations are implicated in FMD. The blood pressure of first-degree relatives was measured using standard devices and, when indicated, with 24-h ambulatory monitoring. Leucocyte DNA was obtained from FMD index cases and ACTA2 sequenced. Thirteen unrelated index cases, aged 2-32 (median 15) years, were recruited. Blood pressure was assessed in 40 first-degree relatives, comprising 22 parents aged 28-58 (median 44) years and 18 siblings aged 3-30 (median 13) years. Hypertension was evident in six (27%) parents but in none of the eight adult siblings. Of the ten screened siblings aged less than 18 years, one teenager was pre-hypertensive (90th-95th centile), the remainder being normotensive. No ACTA2 mutations were found in 13 index cases. Hypertension was evident in 20% of all assessed adult first-degree relatives and is therefore not increased relative to 25% of the adult population. Although hypertensive parents did not undergo angiography to assign FMD status, this observation, together with the lack of hypertension in 18 siblings, indicates that FMD is unlikely to confer an excess hypertension risk in first-degree relatives up to middle-age. Furthermore, in our cohort, FMD was not caused by ACTA2 mutations.

Two recent trials of angiotensin II receptor blockers (ARBs) were performed in children 0-5 years of age. Data from the published reports of these trials together with additional information from the sponsoring drug companies were obtained. Three deaths occurred in the 183 (1.6%) hypertensive children participating in the two trials. At least two of these deaths occurred in children known to be susceptible to drugs acting on the renin-angiotensin system, that is, children with ongoing nephrotic syndrome and acute gastroenteritis. Clinicians who prescribe ARBs in preschool children need to be aware of the risk of drug toxicity especially in children susceptible to intravascular dehydration. Clinicians should consider discontinuing the drugs in the presence of acute diarrhoea.

Safety and efficacy data are presented on the use of mycophenolate mofetil (MMF) in 26 children and adolescents with lupus. Data include therapy before and 12 months after starting MMF. 18 of 26 patients had biopsy-proved lupus nephritis. Group 1 were commenced on MMF induction and/or maintenance therapy (n=14), group 2 converted from azathioprine because of inadequate disease control (n=12). 73% of all (10 (71%) group 1 and 10 (83%) group 2) patients experienced a significant improvement in British Isles Lupus Assessment Group score (from median 9.0 to 3.0). Children with hypocomplementaemia increased their C3 significantly in both groups (0.53-1.15 for group 1 and 0.63-1.2 g/l for group 2, p=0.001), and C4 level only in group 1 (0.08-0.17, p=0.01). Renal function and albuminuria improved in those with active nephritis (p≤0.01). Significant improvements were seen in both groups in haemoglobin, erythrocyte sedimentation rate and lymphocyte counts. Prednisolone dose was weaned in both groups, p<0.05. Side-effects were seen in four patients, but none was judged to be severe enough to discontinue treatment. MMF treatment in this cohort of children with lupus seemed to be safe, well tolerated and effective.

Monocyte chemoattractant protein-1 (MCP-1) has a pathogenic role in murine lupus nephritis (LN). We recruited 25 pediatric and adolescent systemic lupus erythematosus (SLE) patients from our lupus clinic [13 (52%) patients with LN and 12 (48%) lupus non-nephritis patients] and evaluated their urinary and plasma MCP-1 levels compared to adult and childhood controls. The median age and SLE disease duration of patients were 14.4 and 5.5 years, respectively. LN patients had a higher median renal (p=0.01) British Isles Lupus Assessment Group (BILAG) index, with a tendency for higher total BILAG scores (p=0.2). There were significantly increased urinary MCP-1 levels in the LN patients compared to healthy controls (p<0.001) whose values were significantly higher than lupus non-nephritis children (p<0.004). Urinary MCP-1 levels correlated well with total BILAG scores (r=0.82, p=0.04). There were no differences in plasma MCP-1 levels between SLE patient groups and pediatric controls, although the levels in the childhood controls were elevated compared to those of the adult controls (p<0.04). These results provide evidence of increased urinary--but not plasma--MCP-1 levels in children with LN, which correlates well with SLE disease activity as measured by the BILAG index.

Unlabelled: There is still a significant morbidity and mortality associated with childhood-onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side-effects of treatment, especially severe infections and future malignancies. The most commonly cited side-effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side-effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B-lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN., Conclusion: Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab.

Renovascular disease (RVD) is an important cause of hypertension in children, as it often is amenable to potentially curative treatment. Imaging aimed at finding RVD therefore needs to have high sensitivity so as not to miss important findings. Digital subtraction angiography is the gold standard investigation. Doppler ultrasonography, computed tomography (CT) angiography and magnetic resonance (MR) angiography can all be helpful, but none has, at present, high enough sensitivity to rule out RVD in a child with a suggestion of that diagnosis.

Objectives: To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria., Methods: The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis

Background: Prompt diagnosis of urinary tract infection (UTI) in children is needed to initiate treatment but is difficult to establish without urine testing, and reliance on culture leads to delay. Urine dipsticks are often used as an alternative to microscopy, although the diagnostic performance of dipsticks at different ages has not been established systematically., Method: Studies comparing urine dipstick testing in infants versus older children and urine dipstick versus microscopy were systematically searched and reviewed. Meta-analysis of available studies was conducted., Results: Six studies addressed these questions. The results of meta-analysis showed that the performance of urine dipstick testing was significantly less in the younger children when compared with older children (p < 0.01). Positive likelihood ratio (LR) of both nitrite and leucocyte positive 38.54 [95% confidence interval (CI) 22.49-65.31], negative LR for both negative 0.13 (95% CI 0.07-0.25) are reasonably good, and those for young infants are less reliable [positive LR 7.62 (95% CI 0.95-51.85) and negative LR 0.34 (95% CI 0.66-0.15)]. Comparing microscopy and urine dipstick testing, using bacterial colony count on urine culture showed no significant difference between the two methods., Conclusion: Urine dipstick testing is more effective for diagnosis of UTI in children over 2 years than for younger children.

Background: We retrospectively reviewed the medical records of all patients who underwent surgery as part of the treatment of renovascular hypertension (RVH) at our centre between 1979 and 2008. Patients. Thirty-seven children (65% male) with a median age of 7.6 (0.4-17.9) years were identified with a median systolic blood pressure (SBP) of 140 (105-300) mm Hg prior to surgery. Bilateral renal artery stenosis and intra-renal disease were present in 19 (51%) patients, mid-aortic syndrome in 15 (40%), involvement of visceral arteries in eight out of 35 (23%) and coexisting cerebral disease in eight out of 30 (26%) investigated patients., Results: Surgical procedures (n = 53) included (i) nephrectomy (18, of which two unplanned and two secondary due to technical failure), (ii) renovascular surgery on the renal arteries (28, of which 18 had autologous surgery and 10 synthetic grafts inserted for revascularisation) and (iii) aortic reconstruction with (6) and without (1) a synthetic graft. Post-operative complications were haemorrhage (5), septicaemia (5) and chylous ascites (1). There were no perioperative deaths; two children died during follow-up. The SBP post-surgery improved to a median value of 116 (range 90-160) mm Hg. Twelve months after surgery, 16 (43%) children had normal blood pressure without treatment, 15 (41%) normal or improved on one to four antihypertensive drugs and four (11%) unchanged; no data were available for two (5%) children., Conclusion: Surgery effectively treated the hypertension of 90% of our children, when performed in conjunction with medical therapy and interventional radiology. In spite of aggressive surgical treatment, RVH is sometimes a progressive disease.

The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS.

We studied the ability of pre- and postcaptopril renal scintigraphy to predict renovascular disease (RVD) in children. Retrospective review of medical notes and radiology reports of all hypertensive children who had had both pre- and postcaptopril renal scintigraphy with [(99m)Tc] dimercaptosuccinic acid (DMSA) and/or [(99m)Tc] mercaptoacetyltriglycine (MAG3) and digital subtraction angiography (DSA). 81 children aged 1-18 (median 10) years were studied with 62% (51) having a diagnosis of RVD. Main renal artery disease, intrarenal disease, and both main and intrarenal artery disease were present in 25, 14, and 12 patients respectively. The isotope study accurately diagnosed RVD, confirmed by DSA, in 47% (24 of 51) children, with eight false positive studies. The sensitivity, specificity, and positive and negative predictive values of the isotope study to predict RVD were 48%, 73%, 76%, and 51%, respectively. Pre- and postcaptopril renal scintigraphy was unable to predict RVD in children.

Objective: High-dose steroid therapy in children is known to impair growth. What is unknown is the level of steroid therapy at which children continue to grow normally. This study was designed to deduce a dosage of prednisolone compatible with normal growth., Patients and Design: The growth of 41 children (age 1.92-13.2 years) with steroid-dependent nephrotic syndrome (SDNS) was studied using recordings from clinic visits over the course of their follow-up at Great Ormond Street Hospital (study period range 1.38-8.43 years, mean 4.2 years, total 172 years). The height standard deviation score (SDS) and the SDS velocity between clinics were calculated, and compared to the contemporary dose of prednisolone (converted to an equivalent daily dose when on an alternate day regime)., Results: The mean dose of prednisolone was 0.44 mg/ kg/day (range 0.06-1.45 mg/kg/day). The mean change in height SDS velocity over the course of recording was -0.02 SDS/year (boys -0.14 SDS/year, girls +0.16 SDS/year). Overall, there was no negative effect on growth seen at doses of prednisolone of less than 0.75 mg/kg/day. At doses higher than 0.75 mg/kg/day, there was a small decline in height SDS velocity (-0.14 SDS/ year)., Conclusions: Overall, prednisolone treatment in these children was not shown to adversely affect their height SDS. This was true even at doses of prednisolone up to 0.5-0.75 mg/kg/day. There was some decline in height SDS seen during periods of higher steroid use (over 0.75 mg/kg/day), but periods on lower doses allowed for adequate catch up growth.

Factor H (CFH) autoantibodies are associated with atypical hemolytic uremic syndrome (aHUS). Peritransplantation plasma exchange therapy and intensification of immunosuppression, with adjuvant use of anti-CD20 monoclonal antibodies has recently been advocated for cases of CFH-autoantibody associated aHUS. In this report, we describe successful deceased donor renal transplantation in a case of CFH-autoantibody associated aHUS with combined CFHR1 and 3 deficiency in addition to the CFH sequence variant, (cG2850T, pGln950His). CFH-autoantibodies were detected 2 weeks prior to transplantation. Disease recurrence was not observed using basiliximab, an IL2-receptor antagonist and high-dose corticosteroids with mycophenolate mofetil. Adjuvant therapies such as Rituximab nor intensification of plasma therapy were employed. Consequently, careful consideration needs to be given to the use of additional immunosuppression in certain cases of CFH-autoantibody associated aHUS. Serial measurement of CFH-autoantibodies is required in the immediate pre- and posttransplantation period to further clarify their role as a factor in the recurrence of aHUS posttransplantation. Furthermore, delineation of the functional significance of CFH-autoantibodies is warranted in individual cases.

Background: Antibiotic prophylaxis in children who have had urinary tract infection (UTI) to prevent further infection is a common practice. The aim of this study is to reduce the development of further renal scarring by the prevention of recurrent acute pyelonephritis., Methods: A systematic review of randomized controlled trials assessing effectiveness of antibiotic prophylaxis in children who have recovered from a symptomatic UTI and children in whom vesico-ureteric reflux has been identified independent of a history of acute UTI was carried out by systematic search in Medline, EMBASE, the Cochrane Library and CINAHL using keywords and thesaurus terms. Identified trials were independently appraised by two researchers. Data were extracted and synthesized in meta-analyses., Results: A total of 677 children in eight trials were included in the analyses. There was no evidence of difference on meta-analysis of all the included studies, or any of the four subgroups, between the intervention and control groups in recurrence of symptomatic UTI [four trials, RR 0.96 (95% CI: 0.69-1.32]) and incidence of new or progressive renal scarring [four trials, overall RR 1.15 (95% CI: 0.75-1.78)]., Conclusion: Given the lack of evidence on positive benefit of using prophylactic antibiotics for children at risk of developing UTI, routine use of antibiotics for these children is not recommended.

The clinical characteristics and outcomes of children with mid-aortic syndrome (MAS) and the effectiveness of different therapeutic approaches in reducing hypertension are still debated. We conducted a single-centre retrospective review of the records of children with MAS over 30 years. Children with angiographic evidence of a narrowed abdominal aorta were included. Therapeutic approaches included medical management, percutaneous transluminal angioplasty and/or surgical intervention. Thirty-six children had presented at a median age of 2.7 years (10 days-10 years). Thirteen (36%) patients had associated syndromes, and 44% had been diagnosed with cerebrovascular disease. All patients had involvement of multiple arteries. The mortality rate was 8% after a median follow-up period of 4.5 (range 1.1-19.7) years. Among the children who survived, 90% had obtained a reduction in their blood pressure (BP). Of the patients, 76% had had a normal estimated glomerular filtration rate (eGFR) at the last follow-up examination. Seventeen percent (six of 36) had renal dysfunction at presentation. Although MAS is a severe and widespread disease, in most cases it can be effectively treated with a combination of medical, angioplasty and surgical interventions.

Leptospirosis was diagnosed in a child presenting with acute kidney injury, anemia, and thrombocytopenia. Initial symptoms included abdominal pain and nonbloody diarrhea, followed by fever, vomiting, and skin rash. Leptospirosis was suspected and eventually confirmed. Although leptospirosis is uncommon in temperate climates, it is occurring in increasing numbers of participants in water sports, making it a consideration in the differential diagnosis of hemolytic uremic syndrome.

Objectives: To describe the biologic treatment regimens and report the efficacy and safety of biologic therapies in a multicentre series of children with primary systemic vasculitis (PSV)., Methods: This was a retrospective descriptive case series of children with PSV treated with biologic therapy between February 2002 and November 2007. Primary retrospective outcome assessment measures were: daily corticosteroid dose; Birmingham Vasculitis Activity Score (BVAS); and adverse events (including infection rate)., Results: Twenty-five patients median age 8.8 (range 2.4-16) years; 11 male with active PSV (n = 6 with anti-neutrophil cytoplasmic antibody associated vasculitides, n = 11 with polyarteritis nodosa, n = 7 with unclassified vasculitis and n = 1 with Behçet's disease) were treated with biologic agents including infliximab (n = 7), rituximab (n = 6), etanercept (n = 4), adalimumab (n = 1) or multiple biologics sequentially (n = 7). Overall, there was a significant reduction in BVAS from a median of 8.5 (range 5-32) at start of therapy to 4 (range 0-19) at median 32 months follow-up (P = 0.003) accompanied by significant reduction in median daily prednisolone requirement from 1 (range 0.2-2) to 0.25 (range 0-1) mg/kg/day, P = 0.000. For those receiving multiple biologic agents sequentially, a similar clinical improvement was observed with corticosteroid sparing. Infections occurred in 24%, the most severe in those receiving infliximab., Conclusion: Our data provide retrospective evidence of efficacy of these agents, and highlight the associated infectious complications. Further multicentre standardization of treatment protocols and data collection to inform clinical trials of biologic therapy in systemic vasculitis of the young is required.

Severe, symptomatic hypertension occurs uncommonly in children, usually only in those with underlying congenital or acquired renal disease. If such hypertension has been long-standing, then rapid blood pressure reduction may be risky due to altered cerebral hemodynamics. While many drugs are available for the treatment of severe hypertension in adults, few have been studied in children. Despite the lack of scientific studies, some agents, particularly continuous intravenous infusions of nicardipine and labetalol, are preferred in many centers. These agents generally provide the ability to control the magnitude and rapidity of blood pressure reduction and should--in conjunction with careful patient monitoring--allow the safe reduction of blood pressure and the avoidance of complications. This review provides a summary of the underlying causes and pathophysiology of acute severe hypertension in childhood as well as a detailed discussion of drug treatment and the optimal clinical approach to managing children and adolescents with acute severe hypertension.

Background: Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy)., Methods: Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice., Results: Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting., Conclusions: Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation., (2009 Massachusetts Medical Society)