The incidence of and risk factors for late presentation of childhood chronic kidney disease:A systematic review and meta-analysis

BackgroundWhen detected early, inexpensive measures can slow chronic kidney disease progression to kidney failure which, for children, confers significant morbidity and impacts growth and development. Our objective was to determine the incidence of late presentation of childhood chronic kidney disease and its associated risk factors.MethodsWe searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library and CINAHL, grey literature and registry websites for observational data describing children ResultsForty-five sources containing data from 30 countries were included, comprising 19,339 children. Most studies (37, n = 15,772) described children first presenting in kidney failure as a proportion of the chronic kidney disease population (mean proportion 0.43, 95% CI 0.34-0.54). Using this definition, the median incidence was 2.1 (IQR 0.9-3.9) per million age-related population. Risk associations included non-congenital disease and older age. Studies of hospitalised patients, or from low- or middle-income countries, that had older study populations than high-income countries, had higher proportions of late presentation.ConclusionsLate presentation is a global problem among children with chronic kidney disease, with higher proportions seen in studies of hospitalised children or from low/middle-income countries. Children presenting late are older and more likely to have non-congenital kidney disease than timely presenting children. A consensus definition is important to further our understanding and local populations should identify modifiable barriers beyond age and disease to improve access to care

Management of pediatric patients with a failing kidney transplant:A survey of UK‐based renal units

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T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes play a role in this corticosteroid insensitivity.</p> <p>Objectives</p> <p>To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls.</p> <p>Methods</p> <p>Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S) and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for interleukin (IL)-2 and interferon (IFN)γ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ) expression.</p> <p>Results</p> <p>The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (<it>p </it>< 0.05 at concentrations from 0.1-1 μM). There was also a significant reduction (<it>p </it>< 0.05) in the mean inhibitory effect at 1 μM in COPD patients (54.1%) compared to smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically reduced effect of dexamethasone on IL-2 production that did not reach statistical significance. There was no difference in GRα and GRβ expression in follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and smokers (52.9% and 29.7% respectively).</p> <p>Conclusions</p> <p>IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.</p

Paediatric anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis:an update on renal management

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of disorders characterized by necrotizing inflammation of the small to medium vessels in association with autoantibodies against the cytoplasmic region of the neutrophil. Included in this definition are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome). AAV are chronic, often relapsing diseases that can be organ or life threatening. Despite immunosuppression, the morbidity and mortality remain high. Renal involvement contributes significantly to the morbidity with high numbers of patients progressing to end-stage kidney disease. Current therapies have enabled improvements in renal function in the short term, but evidence for long-term protection is lacking. In MPA, renal involvement is common at presentation (90%) and often follows a more severe course than that seen in paediatric GPA. Renal biopsy remains the 'gold standard' in diagnosing ANCA-associated glomerulonephritis. While GPA and MPA are considered separate entities, the two are managed identically. Current treatment regimens are extrapolated from adult studies, although it is encouraging to see recruitment of paediatric patients to recent vasculitis trials. Traditionally more severe disease has been managed with the 'gold standard' treatment of glucocorticoids and cyclophosphamide, with remission rates achieved of between 70 and 100%. Other agents employed in remission induction include anti-tumor necrosis factor-alpha therapy and mycophenolate mofetil. Recently, however, increasing consideration is being given to rituximab as a therapy for children in severe or relapsing disease, particularly for those at risk for glucocorticoid or cyclophosphamide toxicity. Removal of circulating ANCA through plasma exchange is a short-term measure reserved for severe or refractory disease. Maintenance therapy usually involves azathioprine. The aim of this article is to provide a comprehensive review of paediatric AAV, with a focus on renal manifestations, and to highlight the recent advances made in therapeutic management