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Background: The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available. We review the efficacy and safety of tolvaptan and urea in paediatric patients diagnosed with SIADH. Methods: Retrospective review of paediatric inpatients with clinical diagnosis of SIADH. Patients were identified from pharmacy records, based on tolvaptan and urea prescriptions. Relevant information was extracted from patient electronic records. The main outcome measures included: number of days to sodium normalisation, daily change in plasma sodium concentration and maximum increase of plasma sodium concentration in 24hrs . Reported side effects were also captured. Results: Tolvaptan use led to plasma sodium normalisation in 10/13 (77%) within six days (median 2.5 days, range [1,6]) with a median change of sodium concentration of 7 mmol/L (-1,14) within the first 24 hours of treatment. Three patients experienced a change in plasma sodium >10 mmol/l/day but had no apparent side effects. Urea use led to sodium normalisation in 5/6 (83%) patients. Median number of days to normalisation with urea was 2 (1,10) with a median change of plasma sodium concentration of 2 mmol/L (-1,6) within the first 24hours. All patients tolerated tolvaptan and/or urea without unexpected side effects. Conclusions: Tolvaptan and urea appear to be safe and effective when fluid restriction is challenging in paediatric SIADH.

Aim Treatment of frequently relapsing or steroid‐dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long‐term efficacy and safety are still limited. Methods We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid‐dependent, biopsy‐proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re‐treatment. Biochemical and clinical parameters were monitored over an extended follow‐up period of up to 43 months. Results Median steroid‐free survival after RTX was 25 months (range 4–34). Mean relapse frequency decreased from 2.60 ± 0.28 to 0.4 ± 0.19 (P, Summary at a Glance Treatment of steroid‐dependent frequent relapsing nephrotic syndrome is challenging issue. The manuscript examining the efficacy and safety of treatment of rituximab for those patinets give us meaning information in the field of clinical nephrology.

We describe the outcome since 1984 of all children receiving chronic dialysis in our centre for3 months with a minimum follow-up of 5 (median 7.2) years. There were 98 children (61 boys), with a median age at the start of dialysis of 4.2 (range: birth to 16.2) years. Twenty-one children started dialysis at1 year of age and 54 under5 years. Thirty children had significant comorbidity. The median time on dialysis was 1.4 (0.3 to 14.4) years, giving a total dialysis experience of 296 patient-years. Fifty-three children received a renal transplant as their first change of treatment modality, but 31 switched between PD and HD, with a total of 54 changes of dialysis modality pre-transplantation. Twenty-one of the transplanted patients (39%) returned to dialysis. There were a total of 115 transplants in 88 patients. There was a positive increase for both the weight and height SDS for all the age groups while on dialysis, but this did not reach statistical significance. There were 17 deaths over the 20-year study period; of these, 10 died on dialysis. The overall patient survival was 83%. The mortality rate was 2.7 times greater in children who required renal replacement therapy under the age of 5 years. Of the deaths, 76% were in association with comorbid conditions. In conclusion, both a younger age at the start of renal replacement therapy and comorbidity are significant risk factors for death. The number of returnees to dialysis highlights the importance of conserving dialysis access.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with cyclosporin microemulsion (CyA) in pediatric renal recipients. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (

Editor—The branchio-oto-renal (BOR) syndrome was first reported in the last century by Heusinger, but not clinically defined until 1976 by Melnick et al .1 The major clinical features associated with the BOR syndrome are hearing loss, branchial defects, ear pits, and renal anomalies.1 Hearing loss can be conductive, sensorineural, or mixed, ranging from mild to profound deafness.2 Renal abnormalities are also variable, including renal aplasia, hypoplasia, and dysplasia, as well as anomalies of the collecting system.3 Branchial defects including fistulas or cysts and ear pits are often observed, and minor features such as external ear abnormalities, ear tags, and lacrimal duct aplasia are sometimes present. The BOR syndrome is inherited in an autosomal dominant manner and penetrance is high, although expressivity can be extremely variable.3-5 The BOR syndrome gene was localised to 8q following the description of a person with an inherited rearrangement, dir ins(8)(q24.11:q13.3:q21.13) presenting with features of both the branchio-oto (BO) syndrome and trichorhinophalangeal syndrome.6 Linkage analysis confirmed that the BOR syndrome mapped to 8q13.3.7 8 Further fine mapping defined the BOR region to be a 450-650 kb interval.9-12In 1997, the gene was cloned by sequencing P1/PAC clones from a contig spanning the region, yielding sequences homologous to the Drosophila developmental gene eyes absent ( eya). Point mutations and deletions were subsequently detected in the human homologue, EYA1 , in families with the BOR syndrome.13 14 EYA1 consists of 16 coding exons and encodes a 559 amino acid protein. There are two additional EYA1 isoforms and all show significant homology to the Drosophila eya gene, as well as to the murine homologue, constituting a novel gene family.14 15 The Drosophila eya gene is essential in the formation of the fly compound eye and the pathway has …

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 (AUC0-4) in the first week post-transplant is important for successful clinical outcome, and that cyclosporin concentration at 2 h post-dose (C2) provides the optimal single-time point marker for AUC0-4. Clinically, dose management based on C2 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.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.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, C2 correlated more closely with AUC0-4 and with AUC0-12 than did the pre-dose cyclosporin concentration (C0, or trough). Patients achieving C21.5 microg/mL by the fifth postoperative day experienced no acute rejection in the first 6 months, compared with a 50% rejection rate among patients with C21.5 microg/mL (P0.05). Binary logistic regression analysis showed that C2 level1.7 microg/mL was associated with approximately 90% probability of freedom from acute rejection. Analysis of renal function across patients grouped according to cyclosporine exposure (AUC0-4, C2) showed no adverse effects of higher/increased exposure on creatinine or GFR.C2 level provides a more reliable marker for CsA exposure than C0 in pediatric renal transplant recipients, and is more closely predictive of acute rejection risk. A C2 target of 1.7 microg/mL appears appropriate in this population during the immediate post-transplant period in order to maximize clinical benefit.