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Henoch Schonlein Purpura (HSP) is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition. A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year) and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression) was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5) years vs. normal outcome 6.0 (3.7-8.5) years; p<0.01). A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99%) negative predictive value in predicting a normal renal outcome. Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources. The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials. [ABSTRACT FROM AUTHOR]

Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome.Background.Immune cells express heparanase, an endoglycosidase, able to degrade heparan sulfate glycosaminoglycan (HSGAG) in the glomerular capillary wall (GCW) and potentially induce proteinuria. The aim of this study was to determine whether dysregulated heparanase expression is associated with the heavy proteinuria of childhood steroid-sensitive nephrotic syndrome (SSNS).Methods.Plasma and urinary heparanase activity and peripheral blood mononuclear cell (PBMC) mRNA heparanase levels[real-time polymerase chain reaction (PCR)] were measured in children with SSNS in relapse and remission. Plasma and urinary heparanase activity was determined in adult patients with nephrotic syndrome and in age- and gender-matched controls.Results.Plasma heparanase activity was reduced in SSNS with relapse (811.2 units) compared to remission (1147.96 units) (P= 0.003) and control subjects (1390.51 units) (P<0.001). In adult nephrotic syndrome, plasma heparanase activity was significantly lower in patients compared to controls. However, there was no difference between remission and relapse states. In children, urinary heparanase activity/urinary creatinine ratio was highest in SSNS relapse (14.26 units/mg) compared with remission (7.43 units/mg) (P= 0.016) and controls (2.29) (P<0.001). However, PBMC heparanase mRNA expression was not different between these three groups. In adult nephrotic syndrome, urinary heparanase activity/urinary creatinine levels were lower in both remission and relapse compared to controls and there was no difference between remission and relapse states.Conclusion.In childhood SSNS, there is a qualitative and quantitative difference in urinary heparanase activity expression that is not paralleled in adult nephrotic syndrom. These data suggest that dysregulated heparanase expression may play a significant role in the pathogenesis of SSNS, possibly through an abnormality in post-translational control of latent heparanase activation. [ABSTRACT FROM AUTHOR]

Background and aims: This multicenter trial compared immediate‐release tacrolimus (IR‐T) vs prolonged‐release tacrolimus (PR‐T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow‐up efficacy and safety results are reported herein. Materials and methods: Patients, randomized 1:1, received once‐daily, PR‐T or twice‐daily, IR‐T within 4 days of surgery. After a 4‐week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy‐confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout. Results: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR‐T and IR‐T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR‐T n = 1; IR‐T n = 7). Conclusions: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR‐T‐based immunosuppression is effective and well tolerated to 1‐year post‐transplantation. [ABSTRACT FROM AUTHOR]