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Adult nephrologists often look after patients who have been diagnosed with kidney disease in childhood. This does present unique challenges to the adult nephrologist, who may be unfamiliar with the underlying cause of kidney disease as well as the complications of chronic kidney disease (CKD) that may have accumulated during childhood. This review discusses common causes of childhood CKD, in particular congenital anomalies of the kidney and urinary tract (CAKUT), autosomal dominant tubulointerstitial kidney disease (ADTKD), polycystic kidney disease, hereditary stone disease, nephrotic syndrome and atypical haemolytic uraemic syndrome. The long-term consequences of childhood CKD, such as the cardiovascular consequences, cognition and education as well as bone health, nutrition and growth are also discussed.

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.

Relapses of childhood nephrotic syndrome (NS) are frequently precipitated by viral upper respiratory tract infections (URTIs). A review of the literature reveals that in patients with steroid-dependent NS on alternate day corticosteroids, a short course of daily corticosteroid therapy during the course of an URTI may reduce relapse frequency. To assess the effect of a short course of low-dose corticosteroid therapy during the course of an URTI on relapse frequency in patients with steroid-sensitive NS who have not been taking any treatment for a minimum period of 3 months. A double-blind placebo-controlled crossover trial was conducted on 48 patients with idiopathic NS who had not been receiving corticosteroid therapy for a minimum of 3 months. Patients were randomized into two groups. Group A received 5 days of daily prednisolone at 0.5 mg/kg at the onset of an URTI while group B received 5 days of placebo. Both groups were followed up for 1 year and the URTI-induced relapse frequency was noted. A crossover was performed during the next year, with group A receiving placebo and group B receiving prednisolone. Thirty-three patients completed the study. In the treatment group, 115 episodes of URTI led to 11 relapses while in the control group 101 episodes of URTI led to 25 relapses. There was no significant difference between the mean number of URTIs between the treatment and control groups. The treatment group had significantly less relapses compared to the control group (p = 0.014). Within the treatment group, 65.6% did not relapse, while the remainder had a single relapse. In contrast, only 40.6% of the control group remained in remission while 40.6% suffered a single relapse and 18.8% had two or more relapses. Prescribing a short course of daily corticosteroids during an URTI significantly reduces the frequency of URTI-induced relapse in patients with steroid-responsive NS who are off corticosteroid therapy.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance. METHODS: In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls. RESULTS: The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, P=1.59×10-43; odds ratio [OR], 3.39; 95% confidence interval [95% CI], 2.86 to 4.03) and identified two additional loci outside the HLA region on chromosomes 4q13.3 and 6q22.1. The latter contains the calcium homeostasis modulator family member 6 gene CALHM6 (previously called FAM26F). CALHM6 is implicated in immune response modulation; the lead SNP (rs2637678, P=1.27×10-17; OR, 0.51; 95% CI, 0.44 to 0.60) exhibits strong expression quantitative trait loci effects, the risk allele being associated with lower lymphocytic expression of CALHM6. CONCLUSIONS: Because CALHM6 is implicated in regulating the immune response to infection, this may provide an explanation for the typical triggering of SSNS onset by infections. Our results suggest that a genetically conferred risk of immune dysregulation may be a key component in the pathogenesis of SSNS. ispartof: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY vol:30 issue:8 pages:1375-1384 ispartof: location:United States status: published

Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2 ) or a standard eight week course of prednisolone (total dose 2240 mg/m 2 ). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval −0.005 to 0.037) and cost savings (difference −£1673 ($2160; €1930), 95% confidence interval −£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.

BackgroundThe optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome (SSNS) remains uncertain. Most UK centres use an 8-week regimen, despite previous systematic reviews indicating that longer regimens reduce the risk of relapse and frequently relapsing nephrotic syndrome (FRNS).ObjectivesThe primary objective was to determine whether or not an extended 16-week course of prednisolone increases the time to first relapse. The secondary objectives were to compare the relapse rate, FRNS and steroid-dependent nephrotic syndrome (SDNS) rates, requirement for alternative immunosuppressive agents and corticosteroid-related adverse events (AEs), including adverse behaviour and costs.DesignRandomised double-blind parallel-group placebo-controlled trial, including a cost-effectiveness analysis.SettingOne hundred and twenty-five UK paediatric departments.ParticipantsTwo hundred and thirty-seven children presenting with a first episode of SSNS. Participants aged between 1 and 15 years were randomised (1 : 1) according to a minimisation algorithm to ensure balance of ethnicity (South Asian, white or other) and age (≤ 5 or ≥ 6 years).InterventionsThe control group (n = 118) received standard course (SC) prednisolone therapy: 60 mg/m2/day of prednisolone in weeks 1–4, 40 mg/m2of prednisolone on alternate days in weeks 5–8 and matching placebo on alternate days in weeks 9–18 (total 2240 mg/m2). The intervention group (n = 119) received extended course (EC) prednisolone therapy: 60 mg/m2/day of prednisolone in weeks 1–4; started at 60 mg/m2of prednisolone on alternate days in weeks 5–16, tapering by 10 mg/m2every 2 weeks (total 3150 mg/m2).Main outcome measuresThe primary outcome measure was time to first relapse [Albustix®(Siemens Healthcare Limited, Frimley, UK)-positive proteinuria +++ or greater for 3 consecutive days or the presence of generalised oedema plus +++ proteinuria]. The secondary outcome measures were relapse rate, incidence of FRNS and SDNS, other immunosuppressive therapy use, rates of serious adverse events (SAEs) and AEs and the incidence of behavioural change [using Achenbach Child Behaviour Checklist (ACBC)]. A comprehensive cost-effectiveness analysis was performed. The analysis was by intention to treat. Participants were followed for a minimum of 24 months.ResultsThere was no significant difference in time to first relapse between the SC and EC groups (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17; log-rankp = 0.3). There were also no differences in the incidence of FRNS (SC 50% vs. EC 53%;p = 0.7), SDNS (44% vs. 42%;p = 0.8) or requirement for other immunosuppressive therapy (56% vs. 54%;p = 0.8). The total prednisolone dose received following completion of study medication was 5475 mg vs. 6674 mg (p = 0.07). SAE rates were not significantly different (25% vs. 17%;p = 0.1) and neither were AEs, except poor behaviour (yes/no), which was less frequent with EC treatment. There were no differences in ACBC scores. EC therapy was associated with a mean increase in generic health benefit [0.0162 additional quality-adjusted life-years (QALYs)] and cost savings (£4369 vs. £2696).LimitationsStudy drug formulation may have prevented some younger children who were unable to swallow whole or crushed tablets from participating.ConclusionsThis trial has not shown any clinical benefit for EC prednisolone therapy in UK children. The cost-effectiveness analysis suggested that EC therapy may be cheaper, with the possibility of a small QALY benefit.Future workStudies investigating EC versus SC therapy in younger children and further cost-effectiveness analyses are warranted.Trial registrationCurrent Controlled Trials ISRCTN16645249 and EudraCT 2010-022489-29.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 23, No. 26. See the NIHR Journals Library website for further project information.

The Ethics Committee of The Transplantation Society convened a meeting on pediatric deceased donation of organs in Geneva, Switzerland, on March 21 to 22, 2014. Thirty-four participants from Africa, Asia, the Middle East, Oceania, Europe, and North and South America explored the practical and ethical issues pertaining to pediatric deceased donation and developed recommendations for policy and practice. Their expertise was inclusive of pediatric intensive care, internal medicine, and surgery, nursing, ethics, organ donation and procurement, psychology, law, and sociology. The report of the meeting advocates the routine provision of opportunities for deceased donation by pediatric patients and conveys an international call for the development of evidence-based resources needed to inform provision of best practice care in deceased donation for neonates and children. ispartof: Transplantation vol:99 issue:7 pages:1403-9 ispartof: location:United States status: published

Background Nephrotic syndrome (NS) presenting early in life is caused by heterogeneous glomerular diseases. We retrospectively evaluated whether histological diagnosis in children presenting with NS in the first year of life predicts remission or progression to end-stage kidney disease (ESKD). Methods This is a single centre retrospective review of all children diagnosed with NS before one year of age between 1990 and 2009. All subjects had a renal biopsy, which was independently blindly reviewed by a single renal pathologist for the purpose of this study. Results Forty-nine children (25 female) who presented at 0.1–11.6 (median 1.6) months were included with 31 presenting within the first three months of life. Histopathological review diagnostic categories were; 13 Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic complications of the biopsy. Eight children achieved remission (four MesGN, one Finnish type changes, one FSGS, one MCD and one membranous) with patient and renal survival of 73 % and 43 %, respectively, at follow-up duration of 5–222 (median 73) months (with five lost to follow-up). All children with Finnish-type histopathological changes presented within five months of age. Due to the historical nature of the cohort, genetic testing was only available for 14 children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1 and one ITGA3) with none of these nine children achieving remission. All of them had presented within four months of age and required renal replacement therapy, and two died. Conclusions Histopathological findings are varied in children presenting with NS early in life. Whilst groups of histological patterns of disease are associated with differing outcomes, accurate prediction of disease course in a specific case is difficult and more widespread genetic testing may improve the understanding of this group of diseases and their optimal management

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.

Recent studies have suggested adverse outcome for renal allograft rejection associated with dense CD20 lymphocytic infiltrates in transplant renal biopsies. We investigated further the relationship between renal allograft survival and CD20+ lymphocytic infiltrates in renal transplant biopsies from children with graft dysfunction. Fifty consecutive unselected renal transplant biopsies were performed for investigation of acute, chronic or acute on chronic renal allograft dysfunction in 48 children aged 1-17 (median 13.1) years, at 0-155 (median 22) months post-transplantation with median follow up of 24 months post-biopsy. Seventeen (35%) graft losses occurred at 1-163 (median 49) months post-transplantation. There was increased graft loss in those with dense (> 300 cells/hpf) CD20+ lymphocytic infiltrates present on biopsy (p = 0.043). Dense B-cell infiltrates were also associated with increased glucocorticoid requirement in those with acute cellular rejection (p = 0.0015). There were no significant differences in age, sex, HLA-mismatch, type of transplantation, EBV or CMV serology or baseline immunosuppressive regimens between those with or without dense CD20+ infiltrates. Dense CD20+ lymphocytic infiltrates in renal transplant biopsies are associated with adverse clinical outcome, including increased graft loss. This observation raises the possibility of future studies examining the efficacy of B cell depletion therapy in this clinical context.

A retrospective analysis of the value of Tc-99m DTPA DRS in children requiring renal biopsy following transplantation. Thirty-one children following renal transplantation with possible rejection underwent thirty-nine DRS and biopsy within a 72-h period and clinical followed up for 12 months. The biopsy was classified according to the Banff 97. The DRS assessed semi-quantitatively images of renal perfusion and filtration, and the balance between these two images. The clinical notes were reviewed. Based on the biopsy results 15 children had acute rejection, three children chronic rejection, nine children a mixed appearance of both acute and chronic rejection while 12 children had no rejection. Based on the long-term clinical outcome, the DRS had an overall sensitivity of 76% and specificity of 86%. While renal biopsy remains the gold standard for the diagnosis of rejection, if the perfusion and filtration phases of the DRS are analysed separately and the results integrated, there is a possibility of suggesting that acute rejection is not the cause of the increase in creatinine. The DRS provides useful information to the nephrologist when taken in conjunction with the biopsy result and other investigations.

The aims of this study were (1) to ascertain ciclosporin C(2) levels currently being achieved in children with steroid-sensitive nephrotic syndrome (SSNS) and renal transplants (RTs), (2) to determine the feasibility of the use of finger-prick samples for the measurement of ciclosporin levels, and (3) to identify any correlation between hypertrichosis or gingival overgrowth (GO) and level of ciclosporin 2 h post-dose (C(2)). Seventy-two children (39 with SSNS, 33 with RT) participated. Ciclosporin 12 h trough (C(12)) and C(2) levels were measured in venous and finger-prick samples by high-performance liquid chromatography tandem mass spectroscopy. Photographs of the teeth and back were taken for assessment of GO and hypertrichosis. Mean (+/-SD) C(2) levels in the SSNS and RT groups were 512 (+/-181) microg/l and 471 (+/-229) microg/l. There was a highly significant relationship between venous and finger-prick ciclosporin levels (r(2) = 0.96, P0.0001). Fourteen children had severe GO. There was a small, though statistically significant, impact of ciclosporin level on GO (C(2) r(2) = 0.12, P = 0.003 and C(12) r(2) = 0.06, P = 0.038) but no correlation with dose (milligrammes per kilogramme per day or milligrammes per square metre per day) or duration. Seventeen children had moderate or severe hypertrichosis, this being more common in children of South Asian ethnicity (P0.0001). There was no correlation between ciclosporin exposure or duration and hypertrichosis. Finger-prick blood sampling may serve as a practical alternative to venepuncture in children receiving ciclosporin.

Objective: Children with frequently relapsing nephrotic syndrome (FRNS) are usually treated with long term low dose alternate day prednisolone with or without glucocorticoid sparing therapy such as levamisole or cyclosporine A to maintain remission. The degree of hypothalamic-pituitary-adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could place a child at risk of a relapse or adrenal crisis. Study design: To study this possibility further, modified low dose synacthen test (0.5mg) was performed in 32 patients (22M: 10F) aged 3.8-17.6 (mean 9.7) years with NS receiving long-term alternate day prednisolone for over 12 months period. Twelve patients received alternate day prednisolone, 11 alternate prednisolone + levamisole and 9 received alternate prednisolone + cyclosporine A. All patients were followed up for a period of 3 years focusing on the relapse rate. Results: 20/32 (62.5%) had a peak serum cortisol concentration below 500nmol/l suggesting suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the cyclosporine A group. During follow up, 20 children who had a suboptimal cortisol response had a significantly greater number of relapses (95 relapses) when compared to the 12 children with a normal cortisol response with 24 relapses (p=0.01). Conclusions: Children with FRNS receiving long- term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using modified Synacthen test. The children with evidence of HPA suppression are at a greater risk of relapse.

To determine the safety of a 1-week acceptance criteria of sample receipt in laboratory to transfusion commencement in transfusion dependent thalassaemia with respect to alloimmunisation. To determine the safety of electronic issue of blood components in such a setting.Retrospective audit of alloimmunisation (1999-2012) and blood exposure in registered thalassaemia patients at a central London thalassaemia centre where the acceptance criteria for the group and save sample from arrival in the laboratory to the time of issue of blood for transfusion for someone who has been transfused in the last 28 days was 1 week, and there was electronic issue protocol for patients who have always had a negative antibody screen (other than temporary positivity in pregnant women receiving prophylactic anti-D or anti Le-a, Anti Le-b and Anti P1 that are no longer detectable).There were 133 patients with thalassemia variants regularly attending UCLH for review. A total of 105 patients had transfusion dependent thalassaemia (TDT) (7 E-beta thalassaemia, 98 beta thalassaemia major). Ten of the 84 patients who received their transfusions at UCLH were alloimmunised. Seven of them had been alloimmunised prior to arrival at UCLH. Only two patients developed antibodies at UCLH during this period.The prevalence of alloantibody formation of 2% in UCLH transfused patients, with presumptive incidence of 0.01 alloantibodies per 100 units or 0·001 immunisations per person per year compares favourably with other reported series and suggests that 1 week interval with appropriate electronic issue is acceptable practice.

Background: Renal venous thrombosis (RVT) is the most common form of venous thrombosis in neonates, causing both acute and long term kidney dysfunction. Historical predisposing factors include dehydration, maternal diabetes, and umbilical catheters, but recent reports highlight associations with prothrombotic abnormalities. Study: Twenty three patients with neonatal RVT were analysed over 15 years. Predisposing factors, presentation, and procoagulant status were compared with renal outcome using multilevel modelling. Results: Median presentation was on day 1: 19/23 (83%) had pre/perinatal problems, including fetal distress (14), intrauterine growth retardation (five), and pre-identified renal abnormalities (two); 8/18 (44%) had procoagulant abnormalities, particularly factor V Leiden mutations (4/18). Long term abnormalities were detected in 28/34 (82%) affected kidneys; mean glomerular filtration rate was 93.6 versus 70.2 ml/min/1.73 m 2 in unilateral versus bilateral cases (difference 23.4; 95% confidence interval 6.4 to 40.4; p = 0.01). No correlation was observed between procoagulant tendencies and outcome, but presenting renal length had a significant negative correlation: mean fall in estimated single kidney glomerular filtration rate was 3 ml/min/1.73 m 2 (95% confidence interval 3.7 to −2.2; p = 0.001) per 1 mm increase, and kidneys larger than 6 cm at presentation never had a normal outcome. Conclusions: This subgroup of neonatal RVT would be better termed perinatal RVT to reflect antenatal and birth related antecedents. Prothrombotic defects should be considered in all patients with perinatal RVT. Kidney length at presentation correlated negatively with renal outcome. The latter, novel observation raises the question of whether larger organs should be treated more aggressively in future.

Graft thrombosis is an important cause of early (4 weeks) renal graft loss. Reports show that heparin reduces the incidence of early renal allograft thrombosis. Routine peri-operative administration of unfractionated heparin was introduced in our unit in 1994. We conducted a retrospective study of 254 transplants, undertaken in children, between 1987 and 2000. There were 126 children who did not receive heparin (group 1) and 128 who did (group 2). Recipient characteristics and immunosuppression were similar in both groups. The incidence of graft loss secondary to thrombosis was compared between the groups. Variables previously identified with increased risk of graft loss, including donor age, recipient age, cold ischaemia time (CIT), multiple donor vessels, surgical complications, and side of graft donation, were examined using logistic regression. Thrombosis occurred in 14 grafts in group 1 and 11 grafts in group 2 (odds ratio 0.7, 95% confidence interval 0.3-1.6, P=not significant). The mean time to graft loss was similar in groups 1 and 2 (6.6, SD 3.9, range 2-12 days and 7.9, SD 4.4, range 1-14 days, respectively) ( P=0.445). Young recipient age ( P=0.006), young donor age ( P=0.009), increasing CIT ( P=0.007), and surgical complications ( P=0.002) increased the risk of graft thrombosis. A reduction in the incidence of early renal allograft thrombosis upon introduction of heparin was not demonstrated.

Since December 1995, pediatric renal transplant recipients in our unit have received a DMSA scan as soon as possible post-transplant in order to provide a baseline for comparison in the event of subsequent complications. We retrospectively reviewed the case notes and DMSA scans of the 45 patients who underwent a scan within 9 wk of their transplant to see if pre or peri-transplant factors or post-transplant complications were associated with defects on scanning. Forty percentage of scans had defects. The presence of defects was not associated with potential predisposing factors such as patient or donor age, cadaveric or live donation, cold ischemia time, multiple donor vessels, the use of non-heart beating donors, the mean time to scan, the serum creatinine, or the presence of structural renal tract anomalies predisposing to UTI. However, 87% of patients had complications before the scan, including UTI, rejection, acute tubular necrosis, transplant biopsy and drug toxicity. Children with no clinical complications had a significantly reduced risk of a defect (p = 0.035), while biopsy was associated with the presence of defects (p = 0.0034). Twenty patients had one or more follow up DMSA scans: one patient developed a new focal defect. In conclusion, renal transplant defects are frequently found on DMSA scanning even early after transplantation and are non-specifically associated with many different complications.

The optimum range for parathyroid hormone (PTH) levels in children with chronic renal failure (CRF) remains undefined. We aimed to determine growth velocity in children with CRF managed with normal PTH levels. We performed a retrospective case note review of 99 children (77 boys), with a glomerular filtration rate (GFR)41 ml/min per 1.73 m(2), who had at least 2 years of 3-monthly follow-up. The age range at entry was 0.5-6.0 years; data collection was continued until 10 years of age or the commencement of growth hormone or renal replacement therapy. The median GFR was 22 ml/min per 1.73 m(2); over the study period mean serum calcium and phosphate levels were approximately equal to the mid-point of the respective normal ranges. Median PTH levels were equal to the upper limit of the normal range. Height standard deviation score (Ht SDS) at entry was -1.73. During the study period the overall mean change in Ht SDS was +0.3, significantly greater than the no change expected of a normal population ( P=0.004). The median dose of calcium carbonate was 150 mg/kg per day and 1-alpha calcidol 0.015 microg/kg per day. The growth rate was independent of all parameters, including age, PTH levels, the use of enteral feeds, and 1-alpha calcidol prescription. Our results indicate that catch-up growth can occur in infants and children with CRF when medical therapy is aimed at normalizing PTH levels.

Background: There are important differences in CsA pharmacokinetics between adult and pediatric patients, such that pharmacokinetic data can not necessarily be extrapolated from the adult to the pediatric setting. Research in adult renal transplant patients has shown that adequate cyclosporin exposure (AUC 0-4 ) in the first week post-transplant is important for successful clinical outcome, and that cyclosporin concentration at 2 h post-dose (C 2 ) provides the optimal single-time point marker for AUC 0-4 . Clinically, dose management based on C 2 level results in a low incidence of acute rejection in the adult renal transplant population. The study reported here undertook pharmacokinetic profiling in de novo renal transplant patients over a period of 6 months and retrospectively assessed alternative monitoring strategies based on pharmacokinetic findings and clinical outcomes. Methods: This open-label, observational, prospective study was carried out at four UK transplant centers over a period of 6 months in pediatric de novo renal transplant recipients receiving the microemulsion formulation of cyclosporin (Neoral®) according to local protocol. Twelve-hour pharmacokinetic profiles (8-16 blood samples each) were performed on days 5 and 14 and at weeks 4, 13 and 26 post-transplant. Results: Thirty-two patients were recruited (median age 10 yr, range 3-18 yr). At 6 months, patient survival was 100% and graft survival was 91%. The incidence of clinically determined acute rejection was 41% (13 of 32). Six patients discontinued Neoral before 6 months: three due to graft loss, one due to rejection, one due to renal toxicity and one due to hypertrichosis. At all time points studied, C 2 correlated more closely with AUC 0-4 and with AUC 0-12 than did the pre-dose cyclosporin concentration (C 0 , or trough). Patients achieving C 2 > 1.5 μg/mL by the fifth postoperative day experienced no acute rejection in the first 6 months, compared with a 50% rejection rate among patients with C 2 1.7 μg/mL was associated with approximately 90% probability of freedom from acute rejection. Analysis of renal function across patients grouped according to cyclosporine exposure (AUC 0-4 , C 2 ) showed no adverse effects of higher/ increased exposure on creatinine or GFR. Conclusions: C 2 level provides a more reliable marker for CsA exposure than C 0 in pediatric renal transplant recipients, and is more closely predictive of acute rejection risk. A C 2 target of 1.7 μg/mL appears appropriate in this population during the immediate post-transplant period in order to maximize clinical benefit.

Objective To contribute further to the understanding of cognitive and psychosocial outcome of children with end-stage renal disease undergoing long-term peritoneal dialysis. Methods In total, 16 surviving infants at a single centre beginning peritoneal dialysis in the first year of life were studied. The age range of the children at assessment was 1.6–12.1 years. Children were assessed using the Griffiths Mental Development Scales, the Wechsler Intelligence Scale for Children – Third Edition UK, and the Strengths and Difficulties Questionnaire. Information regarding the child's hospital stay and family background was also collated. A Pearson's Product Moment correlation was used to analyse the results. Results Although 67% of the children's scores fell within the average range, 87% were within at least two SDs of the norms (mean IQ = 86.6). Psychosocial adjustment measures revealed that 50% of scores fell within the borderline to abnormal category, suggesting that the frequency of psychological difficulties was above that of the normal population. Conclusions These findings lend support to recent studies indicating that, developmentally, children undergoing long-term peritoneal dialysis are faring better than in the past. This may indeed be a reflection of improvements in renal treatment and diet. The behavioural results suggest the need to monitor psychological adjustment in this group of children.

Prospective Epstein-Barr virus (EBV) surveillance post transplant was undertaken by qualitative polymerase chain reaction testing for EBV DNA in plasma so as to detect EBV viremia as early as possible and thereby attempt to pre-empt post-transplant lymphoproliferative disease by reduction of immunosuppression. Forty-three children (46 transplants) were followed for a median (range) of 15.5 (3-25) months. Thirty-one children (67%) were EBV seropositive pre transplant. Twenty children (44%) developed EBV viremia; of these 9 (60%) were seronegative and 11 (36%) seropositive recipients. Primary infection developed later (median difference 14.2 weeks, P=0.009), was more likely to be symptomatic (odds ratio 2.91, 95% confidence interval 0.95-4.88) and associated with a rise in serum creatinine (odds ratio 6.13, 95% confidence interval 4.13-8.13) than reactivation disease. There was a higher incidence of EBV disease in children receiving quadruple therapy and tacrolimus (odds ratio 13.2, 95% confidence interval 11.5-14.9) compared with those given cyclosporin-based immunosuppression. Immunosuppression was reduced when EBV infection was detected. All children became asymptomatic and renal function returned to normal by a median (range) of 17 (6-52) days, although mild relapses occurred in 3 children. Regular EBV surveillance allowed prompt reduction of immunosuppression and was associated with a good outcome in this group of children.

The majority of infants and young children on peritoneal dialysis (PD) require enteral feeding to achieve their growth potential. We report our experience of gastrostomy feeding in 29 children on PD over 11 years. Fifteen children, median age 3.9 (0.5-13.3) years had a percutaneous gastrostomy (PEG) or Nissen fundoplication and gastrostomy (N and G) or open gastrostomy (OG) before starting PD (group1). Nine children, age 0.7 (0.5-12.4) years, had a N and G or OG (group 2) and 5, age 5.1 (1-15.1) years, a PEG (group 3) after PD catheter insertion/start of PD. In group 1 (257 months gastrostomy feeding with PD), there were 0.6 episodes of peritonitis/patient year. Nine PEGs were replaced electively after 27 (19-50) months, with bleeding from an embedded flange the only complication. One PEG replaced by a button ruptured the track, causing Candida peritonitis. In group 2 (130 months G and PD), there were 1.4 episodes of peritonitis/patient year. Two children developed paraoesophageal hernias, which were successfully repaired. Four children in group 3 developed peritonitis soon after PEG placement. Two transferred to haemodialysis, 1 remained on PD after treatment of Candida peritonitis and 1 subsequently died. Only 2 of the 17 children who have had renal transplants still need gastrostomy feeds. We recommend placement of a PEG or OG if an anti-reflux procedure is necessary prior to starting PD. Placement of a PEG while on PD is contraindicated, but an OG is a safe alternative procedure.

An inadequate nutritional intake is common in infants and young children with chronic and end-stage renal failure (CRF/ESRF), causing poor weight gain and growth retardation. In a programme of enteral feeding (EF), growth, nutritional intake and outcome for oral feeding were evaluated in 35 children with CRF/ESRF, mean (range) age 1.6 (0-4.9) years at start of EF for 30 (12-60) months. Twenty-nine had a glomerular filtration rate of 12.1 (6-26) ml/min per 1.73 m(2) and 6 were on peritoneal dialysis. Mean (SD) weight standard deviation scores (SDSs) in the 0 to 2-year age group (n=26) were -3.3 (1.0) 6 months before EF, -3.1 (1.3) at the start, -1.7 (1. 4) at 1 year, (P=0.0003) and -1.4 (1.8) at 2 years, (P=0.0008). Height SDSs were -2.9 (0.7), -2.9 (1.2), -2.2 (1.2) (P=0.008) and -2. 1 (1.3) (P=0.004). Weight SDSs in the 2 to 5-year age group (n=9) were -2.3 (1.2), -2.0 (1.1), -1.1 (1.3) (P=0.002) and -0.9 (1.0) (P=0.04). Height SDSs were -2.8 (0.6), -2.3 (0.7), -2.0 (0.7) and -2. 0 (0.8). There was no change in energy intake as a percentage of the estimated average requirement, nor was this exceeded. Percentage energy from the EF in the 0 to 2 year age group remained unchanged despite an absolute increase in energy intake with age. Twenty-one have had renal transplants, of whom 86% eat and drink normally. Long-term EF prevents or reverses weight loss and growth retardation in children with CRF/ESRF, with the achievement of significant catch-up growth if started before age 2 years.

Relapses of nephrotic syndrome are often triggered by viral upper respiratory tract infections (URTIs), possibly mediated by cytokine release.To test, in a randomised double-blind placebo-controlled crossover trial, the hypothesis that a small short-term increase in the dose of prednisolone will reduce the release of cytokines and thereby reduce the risk of relapse.Sequential patients receiving low-dose (0.6 mg/kg) prednisolone on alternate days as maintenance therapy were recruited. At the first sign of a presumed viral URTI, all children were examined and randomly allocated to take medicine A or B (containing either prednisolone (5 mg) or placebo) in the first viral URTI, and vice versa in the second. If the criteria for diagnosis of a viral URTI were met, the new medicine was prescribed on alternate days for 1 week at the same dose as that of the prednisolone being taken by the patient on an alternate-day basis. A freshly voided urine sample was tested each morning. The presence of 3+ proteinuria for 3 consecutive days was diagnostic of relapse.48 patients were recruited, and 40 completed the trial (29 male; 11 female). Age at entry ranged from 1.5 to 13.2 (median 5.3) years. The relapse rate after viral URTI was 19/40 (48%) in the placebo group and 7/40 (18%) in the prednisolone group (p = 0.014; two-sided probability using Fisher's exact test).Prescribing prednisolone daily for 7 consecutive days at the same dose as that taken by the patient on an alternate-day basis at the onset of a presumed viral URTI significantly reduces the risk of relapse in children with steroid-dependent nephrotic syndrome.

BACKGROUND Wilms' tumour (WT) occurs bilaterally in approximately 5-7% of affected children. In some patients, complete surgical removal of the malignant tissue cannot be achieved without bilateral total nephrectomy. In Denys-Drash syndrome (DDS), bilateral nephrectomy is indicated both because of the associated nephropathy usually progressing rapidly to end-stage renal failure and because of the high risk of WT development in any residual renal tissue. METHODS Case records of patients with a diagnosis of either bilateral WT (BWT) or DDS, who underwent bilateral nephrectomy and subsequent renal transplantation between 1980 and 1996 at the Hospital for Sick Children, London, were reviewed. RESULTS Allogeneic renal transplantation was performed in two children with BWT and four with DDS, three of whom had developed unilateral WT by the time their kidneys were removed. Renal transplantation was performed 15-49 months after bilateral nephrectomy at a mean age of 45 (26-76) months, with a minimum of 1 year tumour-free survival after completion of chemotherapy in those with WT. One patient died after renal transplantation. Five children had a favourable outcome, with a mean follow-up of 80 (29-121) months post-renal transplantation. CONCLUSION Advances in dialysis and transplantation programmes for young children offer the potential for a marked improvement in the prognosis for patients with BWT and for those with DDS.

BACKGROUND: Bacteriuria is common post-transplant. However, most studies are in adults with a short follow-up. We have assessed the incidence of bacteriuria, predisposing causes and its effect on short and long-term graft function in children. METHODS: The notes of 142 children (67% male) who received 168 kidney transplants (138 cadaveric) between 1987 and 1994 were studied. The mean age at transplantation was 9.0 +/- 4.5 years, and 32 children were transplanted pre-emptively. Diagnoses reflected those found in any children's renal failure programme. RESULTS: Two hundred and thirty one episodes of bacteriuria were detected in 66 patients patients (46%): a rate of one episode per 23 patient months of follow-up. Fifty two percent were during the first year, and 29% of these during the first 4 weeks post-transplant. Forty two children (28%) had recurrences. The incidence was not affected by sex, vesico-ureteric reflux into native kidneys, donor source, circumcision in boys, dialysis pre-transplant or acute rejection. Bacteriuria was significantly more common in patients with a history of bacteriuria before transplant (P < 0.005) and with bladder pathology (P < 0.001). Organisms were predominantly coliforms (41%); 70% were Gram-negative. Sixty percent were resistant to the prescribed antibiotic prophylaxis. There was an associated transient rise in plasma creatinine concentration: mean pre-episode 111 +/- 86 mumol/l vs mean post-episode 134 +/- 108 mumol/l (P < 0.0001). Seventy two percent of episodes were asymptomatic, but even in this group 81% had an associated rise in plasma creatinine (P < 0.001). Despite this, there was no significant decrease in glomerular filtration rate in patients with bacteriuria compared with patients without at the end of follow-up: 50 vs 56 ml/min/1.73 m2 respectively. CONCLUSION: Bacteriuria is common post-transplant, occurring most often in those with bladder pathology or with a history of bacteriuria pre-transplant.

This cross-sectional study aims to assess whether renal transplantation in children under the age of 6 years has an effect on the child's later behaviour and eating and whether this outcome is related to differences in the levels of stress and coping skills shown by the parents. In this small sample of 14 children aged under 8 years, renal transplantation in the pre-school age range did not have any marked adverse effect on the children's emotional or behavioural state. The children's severe eating problems dramatically improved after transplant. Long-term, early tube-feeding does not impair the development of normal feeding patterns in these children. Parental stress levels were not elevated in the post-transplant period and parents tended to use passive coping strategies to manage the chronic illness in their child.

Autosomal recessive polycystic kidney disease causes renal and hepatic dysfunction in childhood. We describe the clinical outcome of 52 children with this diagnosis born between 1950 and 1993. Currently 23 are alive, 24 dead and 5 have been lost to follow-up; 1 has been dialysed and 7 transplanted. Life-table analysis of the patients surviving the 1st month of life revealed an actuarial renal survival of 86% at 1 year and 67% at 15 years. The probability of requiring anti-hypertensive treatment was 39% at 1 year and 60% at 15 years of age. Bleeding from gastro-oesophageal varices occurred in 8 patients at a mean age of 12.5 years, and was preceded by haematological evidence of hypersplenism in 6 of them. The study indicates a relatively good prognosis for patients with this condition who survive the neonatal period and emphasises the importance of early detection and appropriate management of systemic and portal hypertension.

Tailored immunosuppression according to risk stratification for optimal outcome for both immunological and non-immunological risk factors should be the ultimate objective for every child in whom renal transplantation is planned. Renal allograft survival is dependent on the appropriate use of immunosuppressive therapy to prevent acute rejection and chronic allograft nephropathy. Unfortunately, all immunosuppressive therapies, including corticosteroids, have unwanted side effects, including infections, malignancy, nephrotoxicity, hypertension, hyperlipidaemia and diabetes mellitus. However, the most worrying side effects of corticosteroids for children, adolescents and their parents are growth retardation and the cosmetic effects. Consequently, achieving immunosuppressive regimens without corticosteroids would be preferable. The major concern for paediatric nephrologists in the 21st century is no longer acute rejection, as the incidence appears to be decreasing, but infection, particularly EBV and the development of post-transplant lymphoproliferative disease (PTLD). With modern immunosuppressive agents in transplantation, rejection is being traded for infection. The long-term outcome data of PTLD with steroid-free and monoclonal antibody protocols is as yet unknown.

A review was undertaken of the use of alternative immunosuppressive treatment in addition to corticosteroids in a cohort of 429 children with steroid sensitive nephrotic syndrome (SSNS) treated between 1980 and 1994. Two hundred and twenty two children (52%) received at least one course of alternative treatment, 98 (23%) two, and 43 (10%) three. Cyclophosphamide was administered to 196 children (46%); in 181 it was the first course of alternative treatment and in 104 (57%) of those it was also the last ('final course'). Levamisole was given to 56 children (13%) and cyclosporin to 53 (12%). Fifteen children in whom cyclosporin failed were treated with chlorambucil. A few patients received azathioprine or vincristine. Ten children developed secondary steroid resistance, of whom five progressed to chronic renal failure. Acute complications included reversible renal failure, septicaemia, peritonitis, convulsions, and cerebral thrombosis. There were three deaths. It is concluded that half of the referred children with SSNS were deemed to require at least one course of alternative immunosuppressive treatment, and that side effects of the treatment and complications of SSNS are infrequent but occasionally fatal.

Aims Relapses in childhood nephrotic syndrome (NS) are often precipitated by viral upper respiratory tract infections (URTI). This study was undertaken to ascertain the effect of a short course of low dose corticosteroids during URTI on relapse frequency in patients with steroid sensitive NS who are off corticosteroids. Method A placebo-controlled crossover trial was conducted on 48 patients with steroid dependant NS who had been off corticosteroids. Patients recruited were into one of two groups. Group A received 5 days of daily prednisolone at 0.5 mg/kg at the onset of an URTI while group B received 5 days of placebo. Both groups were followed up for one year and the URTI induced relapse frequency was noted. A cross over was performed for the next year with group A receiving placebo and group B receiving prednisolone. The student t-test was used to compare continuous variables. The Fishers exact test was used to compare categorical variables. Of the 48 patients recruited, 33 completed the study. The mean (SD) age at baseline was 12.0 ± 2.4 years for the treatment group and 10.0 ±2.9 years for the placebo group. In the treatment group 113 episodes of URTI led to 11 relapses while in the control group 101 episodes of URTI led to 25 relapses. There was no significant difference between the mean number of URTIs between the treatment and control groups (3.5 ± 1.5 and 3.2 ± 1.4, p = 0.31). The treatment group had a significantly lesser number of relapses compared to the control group (p = 0.014). The majority (65.6%) within the treatment group did not relapse whilst the remaining subjects had a single relapse. In contrast only 40.6% of the control group remained in remission whilst 40.6% suffered from a single relapse and 18.8% had two relapses. Conclusion Administration of a short course of daily corticosteroids during a presumed URTI significantly reduces the frequency of URTI induced relapses in patients with steroid sensitive NS who are off corticosteroids.

Nephrotic syndrome in the first year of life (NSFL) is a heterogeneous group of disorders, the management of which is supportive, as most patients do not respond to immunosuppression. Prognosis is guarded, as the syndrome tends to lead to end-stage renal failure. We describe four cases, all of which went into spontaneous remission. These patients had severe nephrosis that began postnatally at ages 15 days to 7 months and had preceding symptoms of viral infections. One infant had proven pertussis and required ventilation for respiratory failure. Renal biopsies showed varying degrees of mesangial expansion and increased cellularity. Two biopsies showed mild mesangial sclerosis and the other two only scattered globally sclerosed glomeruli. Supportive treatment was started with 20% albumin infusions, diuretics, penicillin, and thyroxine. Angiotensin-converting enzyme (ACE) inhibitors were used to reduce proteinuria in all infants, and one was also treated with indomethacin. The nephrosis gradually resolved, and protein-lowering medications were successfully weaned completely 5–30 months after presentation. The patients were protein free with normal renal function at last follow-up. Investigations including viral studies and autoimmune profiles were negative. Genetic studies for NPHS1, NPHS2, WT1, and LAM-β were negative. We therefore describe a subgroup of NSFL with good prognosis associated with infectious prodromes. This is also the first-described case of pertussis causing nephrotic syndrome.

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.

Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. Polymorphoneutrophil leucocytes (PMNLs) are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We investigated mechanisms of PMNL involvement by measuring tumor necrosis factor α (TNFα) and the novel cytokine, interleukin-8 (IL-8), a potent activator of neutrophils, together with α- antitrypsin-complexed elastase (α1-AT-E) as a marker of neutrophil degranulation, and anti-neutrophil cytoplasmic antibodies (ANCA). IL-8 was not detected in the 17 normal children, but was significantly elevated in 20 of 25 D+ HUS children (P < 0.005), and in three of nine children with non-diarrhea-associated (D—) HUS. Sequential data showed that IL-8 peaked transiently in the circulation, reaching a maximum just before a more protracted burst of α1-AT-E. The IL-8 levels correlated significantly with circulating al-AT-E concentrations (r = 0.50, P < 0.05). In D+ HUS IL-8 levels also correlated with the PMNL count (r = 0.63, P < 0.005), and the highest values were seen in those children who died in the acute phase of the disease. TNFα was raised in only 1 of 16 D+ HUS children and in no patients were ANCA detected. The data suggest that PMNLs in HUS are recruited by IL-8, that this cytokine plays a key role in the PMNL activation which occurs, and that agents which suppress this recruitment and activation might play a therapeutic role in this disorder.

Six children (aged 1.3-6.9 years) were examined with serial duplex Doppler sonography and diethylenetriaminepenta-acetic acid (DTPA) isotope renography in the post-renal transplant period. The resistive index (RI) was derived from sonographic studies and the renal blood flow (RBF) calculated from the isotope scans. The clinical status of the child and the corresponding plasma creatinine level were assessed together with these two parameters. The RIs ranged from 40% to 100% and the RBF from 0% to 16.8%. There were six rejection episodes in four patients. A significant fall in RBF mirrored a rise in plasma creatinine on each occasion, but there was no significant change in RI recorded. There were two graft losses, both associated with renal venous thrombosis. In both cases no significant RBF could be detected on DTPA renography. In one patient, the RBF remained low throughout a period of primary non-function associated with acute tubular necrosis, and increased as primary function was established and the plasma creatinine fell. Throughout this period there was no significant change in the RI. From our preliminary data RBF reflects graft dysfunction more accurately than does the RI.

Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and hypomagnesemia. We retrospectively reviewed radiographic and laboratory data for all patients from a single center who had been screened for an HNF1B mutation. We found heterozygous mutations in 21 (23%) of 91 cases of renal malformation. All mutation carriers had abnormal fetal renal ultrasonography. Plasma magnesium levels were available for 66 patients with chronic kidney disease (stages 1 to 3). Striking, 44% (eight of 18) of mutation carriers had hypomagnesemia (

The aim of this study was to determine whether CNIs can be safely withdrawn in paediatric patients with declining renal allograft function receiving MMF and corticosteroids for long-term immunosuppression following renal transplantation. We performed a retrospective review of paediatric renal transplant recipients who received MMF with corticosteroids at least three months after transplantation with or without CNI in a single centre. Thirty-eight children (71% male), mean age 7.2 +/- 3.7 yr received MMF and corticosteroids, with 29 (76%) receiving a CNI. Mean follow-up was 59.2 +/- 42 months post-MMF commencement and 109 +/- 98.8 months post-transplantation. Patient and renal allograft survival were 100% and 94%, respectively. There was a significant improvement in eGFR after MMF introduction both in children on a CNI and those where the CNI was withdrawn, with stabilisation of eGFR after two yr. There was no significant difference in the number of acute rejection episodes prior to or following introduction of MMF between the groups. MMF in combination with corticosteroids is a safe and effective immunosuppressive regimen in paediatric renal transplantation. Complete withdrawal of CNIs after conversion to MMF should be considered in all patients, to preserve renal function as evidenced by improved eGFR.

Segmental glomerular lesions at the tubular opening, or tip changes, are found in the renal biopsies of adults in many disorders, including some initially considered to show minimal change nephropathy. The hypothesis was that similar tip changes occurred in children. We reviewed a consecutive series of 50 biopsies, diagnosed as minimal change nephropathy, from 49 children. Segmental lesions were found in five biopsies. One biopsy showed lesions at the glomerular hilum. The patient was in remission at follow-up. Four biopsies showed only tip changes. Three patients were in remission, two on no treatment at follow-up, and one on ciclosporin. The other had chronic hepatitis B infection, with persistent proteinuria and segmental lesions at different sites in glomeruli. The other 44 children were nearly all in remission, 18 without treatment at follow-up, and the rest on various immunosuppressants, but one had persistent proteinuria and multiple segmental lesions. Series of childhood minimal change nephropathy, similar to this one, are likely to include cases of the glomerular tip lesion, under the original definition of minimal change nephropathy plus tip changes. This should make little difference in clinical practice, because the clinical course should resemble that of minimal change nephropathy.

A 2-month-old healthy thriving term male infant presented with hypocalcaemic generalised tonic–clonic seizures associated with renal failure (plasma creatinine level 198 μmol/l), severe metabolic acidosis (pH 6.94) and pancytopenia. Renal ultrasound showed bilateral echogenic kidneys, unlike classical nephrocalcinosis with mild prominence of the pelvicalyceal systems (fig 1). Figure 1 Renal ultrasound showed bilateral globally echogenic kidneys with some loss of corticomedullary differentiation and mild prominence of pelvicalyceal systems (the left and right kidneys measured 5.6 and 5.7 cm, respectively, with the 50th centile for age …

In a 6-month, multicenter, randomized, controlled, open-label, parallel-group trial, we investigated the efficacy and safety of adding basiliximab to a standard tacrolimus-based regimen in pediatric renal transplant recipients. Patients18 years received tacrolimus/azathioprine/steroids (TAS, n = 93) or tacrolimus/azathioprine/steroids/basiliximab (TAS + B, n = 99). Target tacrolimus levels were 10-20 ng/mL between days 0-21 and 5-15 ng/mL thereafter. Steroid dosing was identical in both groups. Basiliximab was administered at 10 mg (patients40 kg) or 20 mg (patientsor = 40 kg) within 4 h of reperfusion; the same dose was repeated on day 4. Biopsy-proven acute rejection rates were 20.4% (TAS) and 19.2% (TAS + B); steroid-resistant acute rejection rates were 3.2% and 3.0%, respectively. Patient survival was 100%; graft survival rates were 95% in both arms. The nature and incidence of adverse events were similar in both arms except toxic nephropathy and abdominal pain, which were significantly higher in the TAS + B arm (14.1% vs. 4.3%; p = 0.03 and 11.1% vs. 2.2%; p = 0.02; respectively). Median serum creatinine concentrations at 6 months were 86 micromol/L in the TAS and 91 micromol/L in the TAS + B arm; glomerular filtration rate was 79.4 and 77.6 (mL/min/1.73 m2), respectively. Adding basiliximab to a tacrolimus-based regimen is safe in pediatric patients, but does not improve clinical efficacy.

Background/Aim: To report our experience of paediatric renal transplantation at Great Ormond Street and Royal Free Hospitals since the inception of the programme. Methods: Retrospective review of the patient and transplant survival and influencing factors in the 300 children transplanted between 1973 and 2000. Results: 300 children had received a total of 354 transplants; 56 were living-related donations. The median age at transplantation was 10.3 (range 1.4–17.9) years. Forty-four percent had congenital structural abnormalities of the urinary tract. Forty-six children required a second and 8 a third transplant before transfer to an adult unit. The overall patient survival at 5, 10, and 20 years was 97, 94, and 72%, respectively. In the overall cohort, the donor type (deceased donor or living-related donor) did not affect mortality, nor did age at transplantation, but those transplanted before 5 years of age had a significantly shorter post-transplant survival time (p < 0.0001). Transplant survival (first transplant) for deceased and living-related donors was 66 and 87% at 5 years (p < 0.01), 51 and 54% at 10 years, and 36% at 20 years (deceased-donor transplants only). Although the overall transplant survival was inferior in children transplanted before 2 years of age (p < 0.03), in the most recent cohort (1990–2000), age did not affect the outcome. On multiple regression analysis, the only predictor of transplant survival was the era of transplantation (p < 0.001). The median final height was within the normal range for males and females; 7 patients received growth hormone after transplantation. Conclusions: The outlook for successful transplantation is improving, and in the last decade was unaffected by age at transplantation. The survival of living-related donor transplants is superior to deceased-donor transplants for the first 5 years. From the above data, we can predict that a 10-year-old child receiving a renal transplant in 2000 and on ciclosporin-based immunosuppression can expect a transplant half-life of 13.1 years from a living-related donor and one of 10.8 years from a deceased-donor transplant.

Clinical and histological data of children presenting with steroid-resistant nephrotic syndrome and renal biopsy showing focal and segmental glomerulosclerosis from 1980 with a follow-up of over 10 years were reviewed. There were 66 patients; 38 male and 28 female. Age at onset ranged from 0.4-14.1 years (mean 6.4). Tubular atrophy was present at first biopsy in 50/66, capsular adhesions in 35/66, glomerular tip lesions in 8/66 and mesangial expansion in 31/66 patients. In 51 children, cyclophosphamide was prescribed as the first cytotoxic agent, while 15 received cyclosporine A and complete remission was induced in 43 and 40% of the children, respectively. Complete and stable remission was maintained in 35 children, while 22 had reduction of proteinuria with symptomatic relief. Nine were refractory to cytotoxic therapy. Of the 35 patients who entered complete and stable remission, the renal survival was over 90%, while in the 31 non-responders it was 48% in 10 years. The multivariate analysis using unconditional logistic regression method identified the presence of mesangial expansion (p=0.011) and tip lesions (p=0.005) as the independent predictors of favourable response to cytotoxic therapy and the presence of renal impairment (p=0.008) and extensive focal segmental sclerosis (p=0.025) as independent predictors of unfavourable response.