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1.
BMJ Paediatr Open ; 8(1)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977354

RESUMO

OBJECTIVE: This study aimed to assess the number of prescriptions that were uncollected by caregivers to identify any predisposing systemic themes that may act as barriers to children receiving medications. STUDY DESIGN AND SETTING: Data were retrospectively collected on uncollected prescriptions at a single, tertiary paediatric centre over a 2-month period. This included type and classification of the drug, prescriber specialty, the timing of prescription and the child's registered postcode. Key themes were identified. RESULTS: A total of 124 uncollected prescriptions involving 94 patients were included. 103 (83%) of these were clinic prescriptions, and azathioprine was the most frequently uncollected prescription (n=6, 5%). The uncollected prescriptions most commonly fell under the 'gastrointestinal system' (n=26, 21%) and 'skin' (n=24, 19%) categories, and similarly, 24 (19%) were prescribed by the gastroenterology department and 18 (15%) by dermatology. The mean distance from the child's registered postcode was 8.5±11.8 miles (range 0.5-73.4) with a considerable number of children having a registered postcode greater than 10 miles from the hospital (n=24, 27%). Many children lived in areas corresponding to the lowest decile of the Index of Multiple Deprivation (IMD) (n=38, 42%). CONCLUSION: Urgent interventions and further prospective studies are needed to minimise the barriers that caregivers face in collecting their child's prescription.


Assuntos
Prescrições de Medicamentos , Hospitais Pediátricos , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Criança , Masculino , Feminino , Pré-Escolar , Prescrições de Medicamentos/estatística & dados numéricos , Lactente , Adolescente , Cuidadores/psicologia
3.
Adv Kidney Dis Health ; 31(3): 206-215, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-39004460

RESUMO

Anti-glomerular basement membrane disease is a small-vessel vasculitis involving the kidneys (∼90%) and the lungs (∼60%). Antibodies against the glomerular basement membrane are directly pathogenic in anti-glomerular basement membrane disease; however, recent research has highlighted the critical role of T cells. Novel autoantigens within the glomerular basement membrane are also now recognized. Atypical forms of the disease are reported along with preceding triggers, such as immune checkpoint inhibitors, immunomodulatory drugs, and vaccines. Kidney outcomes in anti-glomerular basement membrane disease remain poor despite significant improvement in patient survival in the last 2 to 3 decades. Treatment typically relies on combined plasmapheresis with intensive immunosuppression. Dialysis dependency at presentation is a dominant predictor of kidney outcome. Histologically, a low (<10%) percentage of normal glomeruli, 100% crescents, together with dialysis dependency at presentation, is associated with poor kidney outcomes. In such cases, an individualized approach weighing the risks and benefits of treatment is recommended. There is a need for better ways to stop the toxic inflammatory activity associated with this disease. In this narrative review, we discuss recent updates on the pathogenesis and management of anti-glomerular basement membrane disease relevant to patients of all ages.


Assuntos
Doença Antimembrana Basal Glomerular , Humanos , Doença Antimembrana Basal Glomerular/terapia , Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/patologia , Plasmaferese , Autoanticorpos/imunologia , Diálise Renal , Imunossupressores/uso terapêutico , Autoantígenos/imunologia , Membrana Basal Glomerular/imunologia , Membrana Basal Glomerular/patologia
4.
J Nephrol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689160

RESUMO

BACKGROUND: Glomerulonephritis inherently leads to the development of chronic kidney disease. It is the second most common diagnosis in patients requiring renal replacement therapy in the United Kingdom. Metabolomics and proteomics can characterise, identify and quantify an individual's protein and metabolite make-up. These techniques have been optimised and can be performed on samples including kidney tissue, blood and urine. Utilising omic techniques in nephrology can uncover disease pathophysiology and transform the diagnostics and treatment options for glomerulonephritis. OBJECTIVES: To evaluate the utility of metabolomics and proteomics using mass spectrometry and nuclear magnetic resonance in glomerulonephritis. METHODS: The systematic review was registered on PROSPERO (CRD42023442092). Standard and extensive Cochrane search methods were used. The latest search date was March 2023. Participants were of any age with a histological diagnosis of glomerulonephritis. Descriptive analysis was performed, and data presented in tabular form. An area under the curve or p-value was presented for potential biomarkers discovered. RESULTS: Twenty-seven studies were included (metabolomics (n = 9)), and (proteomics (n = 18)) with 1818 participants. The samples analysed were urine (n = 19) blood (n = 4) and biopsy (n = 6). The typical outcome themes were potential biomarkers, disease phenotype, risk of progression and treatment response. CONCLUSION: This review shows the potential of metabolomic and proteomic analysis to discover new disease biomarkers that may influence diagnostics and disease management. Further larger-scale research is required to establish the validity of the study outcomes, including the several proposed biomarkers.

5.
J Clin Lab Anal ; 38(7): e25032, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525922

RESUMO

BACKGROUND: Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research. METHODS: A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability. RESULTS: In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring. CONCLUSION: There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.


Assuntos
Teste em Amostras de Sangue Seco , Nefropatias , Humanos , Teste em Amostras de Sangue Seco/métodos , Nefropatias/sangue , Nefropatias/diagnóstico
7.
Artigo em Inglês | MEDLINE | ID: mdl-38211969

RESUMO

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38273659

RESUMO

OBJECTIVES: IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes. METHODS: We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. RESULTS: We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression. CONCLUSIONS: Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.

9.
Clin Kidney J ; 16(12): 2703-2711, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046006

RESUMO

Background: IgA vasculitis (IgAV) is the most common form of childhood vasculitis. Nephritis (IgAVN) occurs in 50% of patients and 1-2% progress to chronic kidney disease stage 5. The pathophysiology of nephritis remains largely unknown, but recent evidence suggests that the complement system may be involved. The aim of this cross-sectional study was to explore whether there is evidence of alternative and/or lectin complement pathway activation in children with IgAVN. Methods: Children with IgAV were recruited and grouped according to proteinuria: IgAVN or IgAV without nephritis (IgAVwoN). Age and sex-matched healthy controls (HCs) were also recruited. Cross-sectional urine and plasma concentrations of complement factor D (CFD), factor B (CFB), and MBL-associated protease 1 (MASP-1) were performed using commercially available enzyme-linked immunoassays. Results: A total of 50 children were included (IgAVN, n = 15; IgAVwoN, n = 20, HCs, n = 15). The mean age was 8.5 ± 3.7 years old, male:female ratio was 1:1. Urinary CFD and CFB concentrations were statistically significantly increased in children with IgAVN (3.5 ± 5.4 µg/mmol; 25.9 ± 26.5 µg/mmol, respectively) compared to both IgAVwoN (0.4 ± 0.4 µg/mmol, P = 0.002; 9.2 ± 11.5 µg/mmol, P = 0.004) and HCs (0.3 ± 0.2 µg/mmol, P < 0.001; 5.1 ± 6.0 µg/mmol, P < 0.001). No statistically significant difference was reported for the plasma concentrations of CFD and CFB. Urinary MASP-1 concentrations were statistically significantly increased in IgAVN (116.9 ± 116.7 ng/mmol) compared to HCs (41.4 ± 56.1 ng/mmol, P = 0.006) and plasma MASP-1 concentrations were increased in IgAVwoN (254.2 ± 23.3 ng/mL) compared to HCs (233.4 ± 6.6 ng/mL, P = 0.046). Conclusion: There is evidence of complement pathway products in the urine of children with IgAVN that warrants further investigation.

10.
Clin Rheumatol ; 42(12): 3189-3200, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37755547

RESUMO

Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.


Assuntos
Vasculite por IgA , Nefrite , Vasculite , Humanos , Criança , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Imunoglobulina A , Nefrite/etiologia , Vasculite/complicações , Vasculite/tratamento farmacológico , Budesonida/uso terapêutico
11.
Pediatr Rheumatol Online J ; 21(1): 85, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580746

RESUMO

BACKGROUND: IgA vasculitis (IgAV) is a small vessel vasculitis that is more common in childhood. Very limited evidence exists on patients who experience an atypical disease course. The aim of this study was to describe a cohort of children diagnosed with recurrent or persisting IgAV to identify any themes associated with their disease course and areas of unmet needs. METHODS: A single centre retrospective study of children diagnosed with recurrent or persisting IgAV at Alder Hey Children's Hospital (Liverpool, UK). Clinical data, including features at presentation and during follow up, potential triggers, abnormal laboratory and histology results, treatment and outcome at last clinical review were retrospectively collected. Key themes were identified. RESULTS: A total of 13 children met the inclusion criteria (recurrent disease, n = 4; persisting disease, n = 9). Median age at first presentation was 10.2 years [2.6-15.5], female:male ratio 1.2:1. Children in the atypical cohort were significantly older than a larger cohort of children who followed a non-complicated disease course (median age 5.5 years (range [0.6-16.7], p = 0.003)). All children re-presented with a purpuric rash (either recurring or persisting), accompanied by joint involvement in 92% of patients (12/13). Disease-modifying anti-rheumatic drugs (DMARDs) were used in 8/13 (62%) children. The median time from first presentation to diagnosis of atypical disease was 18.4 months [5.3-150.8] and the time from first presentation to treatment was 24.1 months [1.8-95.4]. Use of corticosteroids was significantly higher in children with renal involvement (p = 0.026). During follow up, 8/13 (62%) children were admitted at least once, whilst 10/13 (77%) had re-presented at least once to the emergency department. Five (38%) children were referred to psychology services and 7 (54%) children reported feelings of frustration. CONCLUSIONS: This series describes some characteristics of a small cohort of children with atypical IgAV. It also identifies unmet needs in children with atypical IgAV, which includes delays in diagnosis and lengthy waits for treatment, lack of high-quality evidence regarding treatment choices and a high unrecognised disease burden. Further research is needed to study this subgroup of children as evidence is lacking.


Assuntos
Vasculite por IgA , Vasculite , Humanos , Masculino , Criança , Feminino , Lactente , Pré-Escolar , Adolescente , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico , Vasculite por IgA/tratamento farmacológico , Estudos Retrospectivos , Vasculite/diagnóstico , Vasculite/terapia , Progressão da Doença , Doença Crônica , Imunoglobulina A
13.
Pediatr Res ; 94(3): 1166-1171, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37120650

RESUMO

BACKGROUND: Poor literacy can impact achieving optimal health outcomes. The aim of this project was to assess the readability of parent information leaflets (PILs). METHODS: A single-centre study using paediatric PILs. Five readability tests were applied (Gunning Fog Index (GFI), Simple Measure of Gobbledygook (SMOG), Flesch Kincaid Grade Level (FKGL), Coleman-Liau Index (CLI) and Automated Readability Index (ARI)). Results were compared to standards and by subtype. RESULTS: A total of 109 PILs were obtained; mean (±SD) number of characters was 14,365 (±12,055), total words 3066 (±2541), number of sentences 153 (±112), lexical density 49 (±3), number of characters per word 4.7 (±0.1), number of syllables per word 1.6 (±0.1) and number of words per sentence 19.1 (±2.5). The Flesch reading ease score was 51.1 (±5.6), equating to reading age 16-17 years. The mean PIL readability scores were GFI (12.18), SMOG (11.94), FKGL (10.89), CLI (10.08) and ARI (10.1). There were 0 (0%) PILs classed as easy (score <6), 21 (19%) mid-range (6-10) and 88 (81%) were difficult (>10). They were significantly above the recommended reading age (p < 0.0001) and commercial studies were least accessible (p < 0.01). CONCLUSION: Existing PILs are above the national reading level. Researchers should use readability tools to ensure that they are accessible. IMPACT: Poor literacy is a barrier to accessing research and achieving good health outcomes. Current parent information leaflets are pitched far higher than the national reading age. This study provides data to demonstrate the reading age of a large portfolio of research studies. This work raises awareness of literacy as a barrier to research participation and provides tips on how to improve the readability of patient information leaflets to guide investigators.


Assuntos
Compreensão , Letramento em Saúde , Criança , Humanos , Adolescente , Smog , Idioma , Publicações
14.
Pediatr Nephrol ; 38(5): 1491-1498, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36227437

RESUMO

BACKGROUND: Children with immunoglobulin A vasculitis (IgAV Henoch-Schönlein purpura) frequently encounter nephritis (IgAV-N) with 1-2% risk of kidney failure. The pathophysiology of IgAV-N is not fully understood with speculation that complement may contribute. The aim of this study was to identify whether urinary complement proteins are increased in children with IgAV-N. METHODS: A cross-sectional prospective cohort of children with IgAV were recruited together with controls including healthy children and children with systemic lupus erythematosus (SLE). Patients were subdivided according to the presence of nephritis. Urinary C3, C4, C5, and C5a were measured by enzyme-linked immunosorbent assay (ELISA) and corrected for urinary creatinine. RESULTS: The study included 103 children; 47 with IgAV (37 IgAV without nephritis, IgAVwoN; 10 IgAV-N), 30 SLE and 26 healthy children. Urinary complement C3, C4, and C5 were all statistically significantly increased in all children with IgAV compared to SLE patients (all p < 0.05). In patients with IgAV-N, urinary complement C3, C4, C5, C5a were all statistically significantly increased compared to IgAVwoN (C3 14.65 µg/mmol [2.26-20.21] vs. 2.26 µg/mmol [0.15-3.14], p = 0.007; C4 6.52 µg/mmol [1.30-9.72] vs. 1.37 µg/mmol [0.38-2.43], p = 0.04; C5 1.36 µg/mmol [0.65-2.85] vs. 0.38 µg/mmol [0.03-0.72], p = 0.005; C5a 101.9 ng/mmol [15.36-230.0] vs. 18.33 ng/mmol [4.27-33.30], p = 0.01). Using logistic regression, the urinary complement components produced an outstanding ability to discriminate between patients with and without nephritis in IgAV (AUC 0.92, p < 0.001). CONCLUSIONS: Children with IgAV-N have evidence of increased complement proteins present in their urine that may indicate a pathological role and may allow treatment stratification. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Glomerulonefrite , Vasculite por IgA , Lúpus Eritematoso Sistêmico , Nefrite , Vasculite , Humanos , Criança , Vasculite por IgA/complicações , Complemento C3 , Estudos Prospectivos , Estudos Transversais , Imunoglobulina A , Nefrite/diagnóstico , Nefrite/etiologia
15.
Int J Mol Sci ; 23(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36498876

RESUMO

IgA vasculitis (IgAV) is the most common form of paediatric vasculitis, with up to 50% of patients experiencing kidney inflammation. Much remains unknown about IgAV, but it is believed to arise due to galactose-deficient IgA1 promoting an auto-inflammatory response. This study assesses whether urinary IgA can be detected in children with IgAV to allow further evaluation of IgA1 and whether it has any relationship with nephritis. Urinary and serum IgA concentrations were measured using commercially available ELISA kits. Patients were grouped into IgAV nephritis (IgAVN) or IgAV without nephritis (IgAVwoN). Fifty-nine children were included: IgAVN n = 12, IgAVwoN n = 35, and healthy controls (HC) n = 12, with a mean age of 8.2 ± 4.1 years. Urinary IgA concentrations were statistically significantly higher in patients with IgAV (107.1 ± 136.3 µg/mmol) compared to HC (50.6 ± 26.3 µg/mmol; p = 0.027) and IgAVN (229.8 ± 226.3 µg/mmol) compared to both IgAVwoN (65.0 ± 37.8 µg/mmol; p = 0.002) and HC (p < 0.001). Urinary IgA concentrations were able to distinguish between renal status (AUC 0.838, 95%CI [0.704−0.973], p < 0.001) and did not correlate with proteinuria (r = 0.124; p = 0.407). Urinary IgA concentrations are increased in children with IgAVN, and it has the potential to act as a non-invasive biofluid to further evaluate nephritis in this disease.


Assuntos
Vasculite por IgA , Nefrite , Vasculite , Humanos , Criança , Pré-Escolar , Vasculite por IgA/diagnóstico , Imunoglobulina A , Vasculite/diagnóstico
16.
Children (Basel) ; 9(5)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35626799

RESUMO

Chronic kidney disease is a recognised complication of immunoglobulin A vasculitis, (IgAV; formerly Henoch-Schonlein purpura-HSP). The pathophysiology of IgAV and why some patients develop significant renal involvement remains largely unknown. Identifying urinary inflammatory markers could direct targets for earlier intervention. The aim of this cross-sectional exploratory study was to perform a large protein array analysis to identify urinary markers to provide insight into the mechanisms of kidney inflammation in children with established IgAV nephritis (IgAVN). Determination of the relative levels of 124 key proteins was performed using commercially available proteome profiler array kits. Twelve children were recruited: IgAVN, n = 4; IgAV without nephritis (IgAVwoN), n = 4; healthy controls (HCs), n = 4. The urinary concentrations of twenty proteins were significantly different in IgAVN compared to IgAVwoN. The largest fold changes were reported for B-cell activating factor (BAFF), Cripto-1, sex-hormone-binding globulin and angiotensinogen. The urinary levels of complement components C5/C5a and factor D were also significantly elevated in patients with IgAVN. A total of 69 urinary proteins significantly raised levels in comparisons made between IgAVN vs. HCs and nine proteins in IgAVwoN vs. HCs, respectively. This study identified key urinary proteins potentially involved in IgAVN providing new insight into the pathophysiology. Further longitudinal studies with larger cohorts are needed to quantitatively analyse these biomarkers.

17.
Arch Dis Child ; 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35210220

RESUMO

INTRODUCTION: Vancomycin is a recognised cause of drug-induced acute kidney injury (AKI). OBJECTIVE: The aim of this systematic review was to summarise the incidence of, and the risk factors for, vancomycin-associated AKI (v-AKI) in children. DESIGN: A systematic search was performed in November 2020 on the search engines PubMed, Web of Science and Medline, using predefined search terms. The inclusion criteria were primary paediatric studies, intervention with vancomycin and studies that included AKI as an outcome. Study quality was assessed using the relevant Critical Appraisal Skills Programme checklist. The data are reported using descriptive statistics. RESULTS: 890 studies were identified and screened with 25 studies suitable for inclusion. A cohort of 12 730 patients with v-AKI were included and the incidence of v-AKI in children was found to be 11.8% (1.6%-27.2%). The median age of the cohort was 2.5 years (range 0-23) and 57% were male patients. Risk factors that increased the likelihood of v-AKI were concomitant use of nephrotoxic medications, increased trough concentrations and, to a lesser extent, increased dose, longer duration of treatment, impaired renal function and if the patient required paediatric intensive care. CONCLUSIONS: The incidence of v-AKI in children is significant and methods to reduce this risk should be considered. Further prospective interventional studies to understand the mechanisms of nephrotoxicity from vancomycin are needed and targeting risk factors may make vancomycin administration safer.

18.
Pediatr Nephrol ; 37(8): 1713-1719, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34767075

RESUMO

Anti-glomerular basement membrane disease (Anti-GBM), previously known as Goodpasture syndrome, is an extremely rare cause of rapidly progressive glomerulonephritis and chronic kidney disease stage 5 (CKD5) in children. It is associated with acute pulmonary haemorrhage and it has a poor prognosis. It is classified as an autoimmune, small-vessel vasculitis caused by autoantibody formation against the alpha-3 chain in type IV collagen found in the glomerular basement membrane. Evidence of anti-GBM antibodies in serum or histologically are required for diagnosis. Treatment in children is based on very limited adult data and often involves the use of acute apheresis to rapidly remove circulating factors coupled with intensive immunosuppression such as cyclophosphamide and intravenous corticosteroids. There is also an emerging role for the use of biologic agents such as B cell depletion. The evidence base in children with anti-GBM disease is extremely limited. Multi-centre international collaboration is required to provide insight into this disease, better describe its prognosis and work towards improving outcomes. This review article summarises the key features of this disease in children, highlights treatment options and considers areas of unmet need.


Assuntos
Doença Antimembrana Basal Glomerular , Nefrite , Corticosteroides , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Autoanticorpos , Criança , Colágeno Tipo IV , Membrana Basal Glomerular/patologia , Hemorragia , Humanos
19.
Curr Opin Pediatr ; 34(2): 203-208, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34930883

RESUMO

PURPOSE OF REVIEW: Systemic lupus erythematosus is a lifelong, multisystemic disease. Around a fifth of patients present during childhood. Children are recognized to have a more active disease course with more renal involvement (lupus nephritis) when compared with adults. This review article summarizes the current literature surrounding the management of paediatric lupus nephritis. RECENT FINDINGS: International recommendations agree that active, proliferative forms of lupus nephritis are treated with a period of intense induction therapy aimed at inducing remission followed by maintenance immunosuppressive therapy for at least 3 years. Complete response rates in lupus nephritis remain inadequate, in the region of 40-60%, and disease flares are common. Revised histological classification have been proposed but they are yet to be adopted in clinical practice. Lupus nephritis progresses to chronic kidney disease (CKD) stage 5 (kidney failure) in more than 10% of patients within 10 years however the rates of CKD stages 1-4 remain largely unknown. Current trials are focused on the use of biologic agents as adjuncts to current therapy. SUMMARY: There is an urgent need for better outcomes in paediatric lupus nephritis. The use of biomarkers to monitor lupus nephritis and scientific studies to improve our understanding of the pathogenesis offer hope of improved outcomes.


Assuntos
Falência Renal Crônica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Adulto , Criança , Feminino , Humanos , Imunossupressores/uso terapêutico , Rim , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/terapia , Masculino
20.
Pediatr Nephrol ; 36(10): 3033-3044, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33993342

RESUMO

BACKGROUND: Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1-2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N). OBJECTIVE: The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity. METHODS: A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values. RESULTS: One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81-0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-ß-glucosaminidase (NAG) (0.76-0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity. CONCLUSIONS: Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.


Assuntos
Vasculite por IgA , Falência Renal Crônica , Nefrite , Área Sob a Curva , Biomarcadores , Criança , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico , Imunoglobulina A , Falência Renal Crônica/complicações , Masculino , Nefrite/diagnóstico , Nefrite/etiologia
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