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BACKGROUND: Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding. METHODS: The study population comprised children aged < 18 years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression. RESULTS: A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding. CONCLUSIONS: Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.
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BACKGROUND: Primary membranoproliferative GN, including complement 3 (C3) glomerulopathy, is a rare, untreatable kidney disease characterized by glomerular complement deposition. Complement gene mutations can cause familial C3 glomerulopathy, and studies have reported rare variants in complement genes in nonfamilial primary membranoproliferative GN. METHODS: We analyzed whole-genome sequence data from 165 primary membranoproliferative GN cases and 10,250 individuals without the condition (controls) as part of the National Institutes of Health Research BioResource-Rare Diseases Study. We examined copy number, rare, and common variants. RESULTS: Our analysis included 146 primary membranoproliferative GN cases and 6442 controls who were unrelated and of European ancestry. We observed no significant enrichment of rare variants in candidate genes (genes encoding components of the complement alternative pathway and other genes associated with the related disease atypical hemolytic uremic syndrome; 6.8% in cases versus 5.9% in controls) or exome-wide. However, a significant common variant locus was identified at 6p21.32 (rs35406322) (P=3.29×10-8; odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.53 to 2.44), overlapping the HLA locus. Imputation of HLA types mapped this signal to a haplotype incorporating DQA1*05:01, DQB1*02:01, and DRB1*03:01 (P=1.21×10-8; OR, 2.19; 95% CI, 1.66 to 2.89). This finding was replicated by analysis of HLA serotypes in 338 individuals with membranoproliferative GN and 15,614 individuals with nonimmune renal failure. CONCLUSIONS: We found that HLA type, but not rare complement gene variation, is associated with primary membranoproliferative GN. These findings challenge the paradigm of complement gene mutations typically causing primary membranoproliferative GN and implicate an underlying autoimmune mechanism in most cases.
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Complemento C3/inmunología , Glomerulonefritis Membranoproliferativa/genética , Secuenciación Completa del Genoma , Factor Nefrítico del Complemento 3/análisis , Femenino , Glomerulonefritis Membranoproliferativa/etiología , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Masculino , SerogrupoRESUMEN
This review reports the outcomes of paediatric renal transplantation in the United Kingdom over the last 25 years. UK Transplant Registry data on 3236 paediatric renal transplants performed between 1 January 1992 and 31 December 2016 were analysed. Significant improvements in human leucocyte antigen (HLA) matching have been achieved; 84% of recipients received 000 or favourable (0 DR and 0 or 1 B) mismatched kidneys in 2016 compared with 27% in 1992. The median waiting time has increased from 126 days in 1999 to 351 days in 2016. Tacrolimus replaced ciclosporin in most immunosuppressive regimens after 2002. Renal transplant outcome has improved significantly, mainly because of a reduction in early graft loss. One-year donation after brain death renal allograft survival for those transplanted from 2012 to 2016 was 98%, compared with 72% for those transplanted from 1987 to 1991. Renal allograft survival for first kidney only transplants at 1, 5, 10, 20 and 25 years were 89%, 79%, 65%, 42% and 33% respectively. Superior survival with living donor was maintained throughout the study period with 25-year graft survival at 33% compared with 31% from deceased donor (P < 0.0001). Changes in immunosuppression regimens, improvements in HLA matching and a reduction of cold ischaemia time may in part explain the improvements in graft survival.
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Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Trasplante de Riñón/tendencias , Donadores Vivos , Adolescente , Incompatibilidad de Grupos Sanguíneos , Niño , Preescolar , Ciclosporina/administración & dosificación , Citomegalovirus , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Humanos , Inmunosupresores/administración & dosificación , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/mortalidad , Masculino , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Obtención de Tejidos y Órganos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. METHODS: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). RESULTS: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. CONCLUSIONS: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.
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Fallo Renal Crónico/terapia , Trasplante de Riñón/estadística & datos numéricos , Síndrome del Abdomen en Ciruela Pasa/complicaciones , Terapia de Reemplazo Renal/estadística & datos numéricos , Adolescente , Niño , Preescolar , Estudios de Cohortes , Europa (Continente) , Humanos , Riñón/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Masculino , Síndrome del Abdomen en Ciruela Pasa/mortalidad , Sistema de Registros , Terapia de Reemplazo Renal/métodos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug treatments of IC have a limited effect in improving walking distance. Padma 28, a Tibetan herbal preparation, has been used to treat IC, but there is debate as to whether Padma 28 produces a clinical benefit beyond the placebo effect. This is an update of a review first published in 2013. OBJECTIVES: To determine whether Padma 28 is effective, compared with placebo or other medications, in increasing pain-free and maximum walking distance for patients with intermittent claudication. SEARCH METHODS: For this update the Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (September 2015), the Cochrane Register of Studies ((CENTRAL) (2015, Issue 8)) and clinical trials databases. SELECTION CRITERIA: Randomised controlled trials of Padma 28 compared with placebo or other pharmacological treatments in people suffering from IC. DATA COLLECTION AND ANALYSIS: All review authors independently assessed the selected studies and extracted the data. Risk of bias was evaluated independently by two review authors. Depending on the data provided in the individual trials, we extracted mean or median walking distance at the end of the trial, or change in walking distance over the course of the trial, or both. Where not provided, and whenever possible, the statistical significance of differences in these parameters between treatment and placebo groups in individual trials was calculated. Where possible, data were combined by meta-analysis. MAIN RESULTS: No new trials were identified in the search for this review update. In total five trials involving 365 participants were included in this review. All trials compared Padma 28 with placebo for at least 16 weeks of follow-up. Pain-free and maximum walking distances both increased significantly in the groups treated with Padma 28, with no significant change in the placebo group. In general, the studies presented results comparing the treatment arms before and after treatment but made no comparisons between the Padma 28 and placebo groups. Pooled data of maximum walking distance after treatment with Padma 28 and placebo from two studies (193 participants) indicated a higher maximum walking distance (mean difference (MD) 95.97 m, 95% confidence interval (CI) 79.07 m to 112.88 m, P < 0.00001, very low quality evidence) in the Padma 28 group compared with placebo. The clinical importance of these observed changes in walking distance is unclear as no quality of life data were reported. There was no effect on ankle brachial index (ABI): change in ABI values between baseline and six months follow up MD -0.01, 95% CI -0.07 to 0.05, 1 study, 56 participants, P = 0.72, very low quality evidence). Mild side effects, especially gastrointestinal discomfort, tiredness and skin eruption, were reported but this outcome was not different between the Padma 28 and placebo groups (odds ratio 1.09, 95% CI 0.42 to 2.83, four studies, 231 participants, P = 0.86, very low quality evidence). AUTHORS' CONCLUSIONS: Some evidence exists from individual trials to suggest that Padma 28 may be effective in increasing walking distances, at least in the short term (four months), in people with IC. Side effects do not appear to be a problem. However, the longer term effects of treatment are unknown and the clinical significance of the improvements in walking distance are questionable. Moreover, the quality of the evidence is limited by the small sample size of the available trials, limited reporting of statistical analyses that compared treatment groups, and relatively high withdrawal rates that were linked to the outcome. That is, patients were withdrawn if they failed to improve walking distance. There was also evidence of publication bias. We therefore feel there is currently insufficient evidence to draw conclusions regards the effectiveness of Padma 28 in the routine management of IC. Further well-designed research would be required to determine the true effects of this herbal preparation.
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Claudicación Intermitente/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Caminata , Humanos , Efecto Placebo , Extractos Vegetales/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
BACKGROUND: Peripheral arterial disease (PAD) may cause occlusions (blockages) in the main arteries of lower limbs. One treatment option is bypass surgery using autologous (the patient's own tissue) vein graft or prosthetic (artificial) graft. A number of factors influence occlusion rates in these patients, including the material used. To prevent graft occlusion patients are usually treated with antiplatelet, antithrombotic drugs, or a combination of both. OBJECTIVES: To determine the effects of antiplatelet agents for the prevention of thrombosis in people with lower limb atherosclerosis who were undergoing femoropopliteal or femorodistal bypass grafting. Outcomes included the overall success of therapy (graft patency and limb salvage rates) and complications of treatment. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched June 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 5). We sought additional trials through screening the reference lists of relevant papers. SELECTION CRITERIA: Two review authors, RB and AL, independently reviewed studies found in the search and evaluated them based on the inclusion and exclusion criteria, resolving disagreements through discussion. DATA COLLECTION AND ANALYSIS: RB and AL independently extracted details of the selected studies for the update. We compared the treatment and control groups for important prognostic factors and differences described. If any data were unavailable, we sought further information from study authors. We synthesised data by comparing group results. We addressed unit of analysis issues by subgroup analysis. MAIN RESULTS: We include 16 studies with 5683 randomised participants. Nine different treatment groups were evaluated: aspirin (ASA) or aspirin and dipyridamole (ASA/DIP) versus placebo or nothing (six studies); ASA or ASA/DIP versus pentoxifylline (two studies); ASA/DIP versus indobufen (one study); ASA or ASA/DIP versus vitamin K antagonists (two studies); ASA/DIP versus low molecular weight heparin (one study); ticlopidine versus placebo (one study); ASA versus prostaglandin E1 (one study); ASA versus naftidrofuryl (one study); and clopidogrel and ASA versus ASA alone (one study). The treatment comparisons were evaluated separately, and, where possible, we performed subgroup analysis for venous grafts and prosthetic grafts and at different follow-up time points. The quality of evidence was low to moderate as many of the treatment comparisons had very few studies to contribute data, several of the included studies had unit of analysis issues, the treatment dosages varied between studies, and data for many outcomes important to this review were not given in any of the studies, or differed greatly between studies. Overall study quality was moderate, with the largest problem being that the majority of studies did not describe their methods of randomisation, allocation concealment or blinding of outcome assessors, leading to risk ratings of 'unclear'. The other main issue with study quality was studies not blinding participants or personnel.The treatment comparison with the most number of included studies, which allowed for robust conclusions, was that of aspirin (ASA) or ASA and dipyridamole (ASA/DIP) versus placebo or nothing, covered by six studies. For this treatment group, there was improved graft patency in the ASA or ASA/DIP treatment group, odds ratio (OR) 0.42 (95% confidence interval (CI) 0.22 to 0.83; P = 0.01; 952 participants). This effect was not seen for venous grafts alone at any of the time points, but was observed for all time points in prosthetic grafts, including the final time point of 12 months (OR 0.19, 95% CI 0.10 to 0.36; P < 0.00001; 222 participants). Only a single study evaluated secondary patency, for which there was no difference between treatment groups. For the comparison ASA or ASA/DIP versus placebo or nothing there was no difference for any of the side effects, including general, gastrointestinal, bleeding and wound/graft infection. Amputations, cardiovascular events and mortality were also similar between the treatment groups. The comparison of ASA or ASA/DIP versus vitamin K antagonists included two studies, one of which was very large, with over 2000 participants. There were no differences between treatment for primary graft patency at three, six, 12 or 24 months, and there was also no evidence of a difference for limb amputation, cardiovascular events or mortality. One large study (851 participants) evaluated clopidogrel and ASA versus ASA alone, and for all grafts there was no evidence of a difference of primary patency at 24 months. There was evidence of increased total bleeding in the clopidogrel and ASA group (OR 2.65, 95% CI 1.69 to 4.15) from an increase in mild (OR 2.34, 95% CI 1.37 to 4.00), and moderate bleeding (OR 4.13, 95% CI 1.37 to 12.45), but no difference in severe or fatal bleeding. There was no difference between the treatment groups for limb amputation or mortality. For the remaining treatment comparisons there is not currently enough evidence to draw any robust conclusions about the efficacy or safety of the treatment on graft patency after peripheral bypass. AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin or with aspirin plus dipyridamole had a beneficial effect on primary patency of peripheral bypass grafts compared to placebo or no treatment. This effect was not evident when evaluating venous grafts alone, but antiplatelet therapy did have a beneficial effect on patency in those who had prosthetic grafts. There was no evidence of differences in side effects (including general, gastrointestinal, bleeding or infection), amputation, cardiovascular events or mortality between the treatment groups. However, the number of participants included in this analysis might be too small to detect a statistically significant effect for side effects, amputation, cardiovascular morbidity or mortality. We found no difference in primary graft patency when aspirin or aspirin with dipyridamole was compared to a vitamin K antagonist or when clopidogrel with aspirin was compared to aspirin alone. However, there was evidence of increase bleeding in the clopidogrel with aspirin group for the latter comparison. The remaining six treatment comparisons did not include enough data to draw any robust conclusions about their efficacy or safety at this time.
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Oclusión de Injerto Vascular/prevención & control , Enfermedades Vasculares Periféricas/cirugía , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis/prevención & control , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Anticoagulantes/uso terapéutico , Arteriosclerosis/cirugía , Aspirina/uso terapéutico , Dipiridamol/uso terapéutico , Oclusión de Injerto Vascular/etiología , Humanos , Claudicación Intermitente/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Grado de Desobstrucción VascularRESUMEN
INTRODUCTION: Adults with childhood-onset chronic kidney disease (CKD) have an increased risk of cardiovascular disease. First-phase ejection fraction (EF1), a novel measure of early systolic function, may be a more sensitive marker of left ventricular dysfunction than other markers in children with CKD. OBJECTIVE: To examine whether EF1 is reduced in children with CKD. METHODS: Children from the 4C and HOT-KID studies were stratified according to estimated glomerular filtration rate (eGFR). The EF1 was calculated from the fraction of left ventricular (LV) volume ejected up to the time of peak aortic flow velocity. RESULTS: The EF1 was measured in children ages 10.9 ± 3.7 (mean ± SD) years, 312 with CKD and 63 healthy controls. The EF1 was lower, while overall ejection fraction was similar, in those with CKD compared with controls and decreased across stages of CKD (29.3% ± 3.7%, 23.5% ± 4.5%, 19.8% ± 4.0%, 18.5% ± 5.1%, and 16.7% ± 6.6% in controls, CKD 1, 2, 3, and ≥ 4, respectively, P < .001). The relationship of EF1 to eGFR persisted after adjustment for relevant confounders (P < .001). The effect size for association of measures of LV structure or function with eGFR (SD change per unit change in eGFR) was greater for EF1 (ß = 0.365, P < .001) than for other measures: LV mass index (ß = -0.311), relative wall thickness (ß = -0.223), E/e' (ß = -0.147), and e' (ß = 0.141) after adjustment for confounders in children with CKD. CONCLUSIONS: Children with CKD exhibit a marked and progressive decline in EF1 with falling eGFR. This suggests that EF1 is a more sensitive marker of LV dysfunction when compared to other structural or functional measures and that early LV systolic function is a key feature in the pathophysiology of cardiac dysfunction in CKD.
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Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Adulto , Niño , Humanos , Función Ventricular Izquierda/fisiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/complicaciones , Ventrículos Cardíacos/diagnóstico por imagen , RiñónRESUMEN
OBJECTIVES: Remdesivir decreases the risk of SARS-CoV-2 infection progressing to severe disease in adults. This study evaluated remdesivir safety and pharmacokinetics in infants and children. METHODS: This was a phase 2/3, open-label trial in children aged 28 days to 17 years hospitalized for polymerase chain reaction-confirmed SARS-CoV-2 infection. Participants received for ≤10 days once-daily intravenous remdesivir doses defined using physiologically based pharmacokinetic modeling (for ≥40 kg, 200 mg day 1, then 100 mg/day; for age ≥28 days and ≥3 to <40 kg, 5 mg/kg day 1, then 2.5 mg/kg/day). Sparse pharmacokinetic samples were analyzed using population-pharmacokinetic approaches for remdesivir and metabolites GS-704277 and GS-441524. RESULTS: Among 53 participants, at enrollment the median (Q1, Q3) number of days of COVID-19 symptoms was 5 (3, 7) and hospitalization was 1 (1, 3). Underlying conditions included obesity in 19 (37%), asthma in 11 (21%), and cardiac disorders in 11 (21%). Median duration of remdesivir treatment was 5 days (range, 1-10). Remdesivir treatment had no new apparent safety trends. Two participants discontinued treatment because of adverse events including elevated transaminases; both had elevated transaminases at baseline. Three deaths occurred during treatment (and 1 after). When compared with phase 3 adult data, estimated mean pediatric parameters (area under the concentration-time curve over 1 dosing interval, AUCτ, Cmax, and Cτ) were largely overlapping but modestly increased (remdesivir, 33%-129%; GS-704277, 37%-124%; GS-441524, 0%-60%). Recovery occurred for 62% of participants on day 10 and 83% at last assessment. CONCLUSIONS: In infants and children with COVID-19, the doses of remdesivir evaluated provided drug exposure similar to adult dosing. In this study with a small sample size, no new safety concerns were observed.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , COVID-19 , Niño Hospitalizado , Adulto , Lactante , Humanos , Niño , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Pirroles , TransaminasasRESUMEN
INTRODUCTION: To describe the demographics of the paediatric renal replacement therapy (RRT) population under the age of 18 years in the UK and to analyse changes in demography with time. METHODS: Data were collected from all 13 paediatric renal centres within the UK. A series of crosssectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients. RESULTS: A total of 861 children and young people under 18 with established renal failure (ERF) were receiving treatment at paediatric nephrology centres in 2012. At the census date, 80.2% had a functioning transplant, 10.6% were receiving haemodialysis (HD) and 9.2% were receiving peritoneal dialysis (PD). In patients aged <16 years the prevalence of ERF was 56.7 pmarp and the incidence 9.0 pmarp. A third of the prevalent patients had one or more reported comorbidities. At transfer to adult services, 81.5% of patients had a functioning renal transplant. Preemptive transplantation was seen to occur in a third of children starting RRT under 16 years, with lower rates seen in girls and ethnic minorities. Over the past 15 years for those referred early, there has been a rise in pre-emptive transplantation rates, rising from 26.2% in 1998-2002 to 36.3% in 2008-2012. Over the same period there has also been an increase in living donation from 7.1% to 18%. Survival in childhood amongst children starting RRT was the lowest in those aged less than two years. CONCLUSIONS: The findings of this report are similar to last year with continued improvement in data quality and electronic submission of data returns. The data provided in this report show slowly increasing trends of incidence and prevalence in children with established renal failure.
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Informes Anuales como Asunto , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Trasplante de Riñón/tendencias , Sistema de Registros/estadística & datos numéricos , Adolescente , Factores de Edad , Áreas de Influencia de Salud/estadística & datos numéricos , Niño , Preescolar , Comorbilidad , Estudios Transversales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Donadores Vivos/estadística & datos numéricos , Estudios Longitudinales , Masculino , Diálisis Peritoneal/estadística & datos numéricos , Prevalencia , Tasa de Supervivencia , Obtención de Tejidos y Órganos/tendencias , Reino Unido/epidemiologíaRESUMEN
INTRODUCTION: The British Association for Paediatric Nephrology Registry (BAPN) was established to analyse data related to renal replacement therapy (RRT) in children. The registry receives data from the 13 paediatric nephrology centres in the UK. This chapter aims to provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure (ERF). METHODS: Data returns included a mixture of electronic (92%) and paper (8%) returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence. RESULTS: Anthropometric data confirmed that children receiving RRT were short compared to healthy peers. Amongst patients with a height of <2SD between 2001 and 2012, 29.2%were receiving growth hormone if they were on dialysis compared to 11.9% if they had a functioning transplant. Prevalence rates of overweight and obese status in children with ERF remain concerningly high. Blood pressure control remained challenging with wide inter-centre variation although this was significantly better in children with a functioning transplant. Over a quarter of haemodialysis patients and 17.3% of peritoneal dialysis patients were anaemic, compared to only 8.3% of transplanted patients. ESA use in the dialysis population exceeded 90% amongst anaemic patients. The control of renal bone disease remained challenging. CONCLUSIONS: Optimising growth and reducing prevalent excess weight in children on RRT remains challenging. The likelihood of complete electronic reporting in the near future with plans for quarterly reporting in the format of the recently finalised NEW paediatric dataset will hopefully improve quality of data and their reporting, allowing improvements in patient care.
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Informes Anuales como Asunto , Fallo Renal Crónico/terapia , Trasplante de Riñón/estadística & datos numéricos , Obesidad/epidemiología , Sistema de Registros/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Adolescente , Anemia/epidemiología , Bicarbonatos/sangre , Presión Sanguínea , Estatura , Índice de Masa Corporal , Calcio/sangre , Áreas de Influencia de Salud/estadística & datos numéricos , Niño , Preescolar , Estudios Transversales , Eritropoyetina/sangre , Tasa de Filtración Glomerular , Hormona del Crecimiento/uso terapéutico , Adhesión a Directriz/estadística & datos numéricos , Hematínicos/uso terapéutico , Hemoglobinas/metabolismo , Humanos , Lactante , Recién Nacido , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Trasplante de Riñón/normas , Estudios Longitudinales , Hormona Paratiroidea/sangre , Fosfatos/sangre , Guías de Práctica Clínica como Asunto , Prevalencia , Diálisis Renal/normas , Reino Unido/epidemiologíaRESUMEN
AIMS: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time. METHODS: Data were collected from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of paediatric RRT patients. RESULTS: A total of 856 children and young people under 18 with ERF were receiving treatment at paediatric nephrology centres in 2011. At the census date, 80.1% had a functioning transplant, 10.5% were receiving peritoneal dialysis (PD) and 9.4% were receiving haemodialysis (HD). In patients aged <16 years the prevalence of ERF was 56.8 pmarp and the incidence 8.3 pmarp. Analysis of trends over the last 15 years shows that both incidence and prevalence are increasing. A third of the prevalent patients had one or more reported comorbidities. At transfer to adult services, 86% of patients had a functioning renal transplant. Pre-emptive transplantation was seen to occur in 31% of children starting RRT under 16 years, with lower rates seen in girls and ethnic minorities. Survival in childhood amongst children starting RRT was the lowest in those aged less than 2 years. CONCLUSIONS: The data provided in this report show increasing trends over 15 years in the incidence and prevalence of established renal failure. This is important for the planning of the provision of care for children needing renal replacement therapy. Further research is required to understand the gender and ethnic differences in pre-emptive transplantation rates and the reduced survival amongst children aged less than 2 years.
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Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/rehabilitación , Sistema de Registros , Terapia de Reemplazo Renal/mortalidad , Terapia de Reemplazo Renal/tendencias , Adolescente , Distribución por Edad , Informes Anuales como Asunto , Niño , Preescolar , Femenino , Encuestas Epidemiológicas , Humanos , Lactante , Recién Nacido , Masculino , Nefrología/estadística & datos numéricos , Nefrología/tendencias , Prevalencia , Factores de Riesgo , Distribución por Sexo , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The British Association for Paediatric Nephrology Registry was established to analyse data related to renal replacement therapy (RRT) in children. The registry receives data from the 13 paediatric nephrology centres in the UK. AIMS: To provide centre speciï¬c data so that individual centres can reï¬ect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure. METHODS: Data returns have been a mixture of electronic and paper returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence. RESULTS: Anthropometric data conï¬rmed that children receiving RRT were short compared to healthy peers. Amongst patients with a height of <2 SD between 2001 and 2011, 31% were receiving growth hormone if they were on dialysis compared to 10% if they had a functioning transplant. Blood pressure control remained challenging with wide inter-centre variation although this was signiï¬cantly better in children with a functioning transplant. Over a third of haemodialysis patients and a quarter of peritoneal dialysis patients were anaemic, compared to only 7% of transplanted patients. ESA use in the dialysis population exceeded 90% amongst anaemic patients. The control of renal bone disease remained challenging. CONCLUSIONS: Optimizing growth in children on RRT remained challenging and the control of bone biochemistry in children on dialysis was imperfect. The likelihood of complete electronic reporting in the near future with plans for quarterly reporting in the format of the recently ï¬nalised NEW paediatric dataset will hopefully improve quality of data and their reporting, allowing improvements in patient care.
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Hemoglobinas/análisis , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/rehabilitación , Sistema de Registros , Terapia de Reemplazo Renal/estadística & datos numéricos , Adolescente , Informes Anuales como Asunto , Causalidad , Niño , Preescolar , Femenino , Encuestas Epidemiológicas , Humanos , Lactante , Recién Nacido , Fallo Renal Crónico/diagnóstico , Masculino , Nefrología/estadística & datos numéricos , Nefrología/tendencias , Prevalencia , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Intermittent claudication is pain caused by chronic occlusive arterial disease that develops in a limb during exercise and is relieved with rest. Most drug treatments of intermittent claudication have a limited effect in improving walking distance. Padma 28, a Tibetan herbal preparation, has been used to treat intermittent claudication, but there is debate as to whether Padma 28 produces a clinical benefit beyond the placebo effect. OBJECTIVES: To determine whether Padma 28 is effective, compared with placebo or other medications, in increasing pain-free and maximum walking distance for patients with intermittent claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched April 2013), CENTRAL (2013, Issue 3) and clinical trials databases. In addition, a pharmaceutical company was contacted. SELECTION CRITERIA: Randomised controlled trials of Padma 28 compared with placebo or other pharmacological treatments in people suffering from intermittent claudication. DATA COLLECTION AND ANALYSIS: All review authors independently assessed the selected studies and extracted the data. Risk of bias was evaluated independently by two review authors. Depending on the data provided in the individual trials, we extracted mean or median walking distance at the end of the trial, or change in walking distance over the course of the trial, or both. Where not provided, and whenever possible, the statistical significance of differences in these parameters between treatment and placebo groups in individual trials was calculated. Where possible, data were combined by meta-analysis. MAIN RESULTS: Five trials involving 365 participants were identified. All trials compared Padma 28 with placebo for at least 16 weeks of follow-up. Pain-free and maximum walking distances both increased significantly in the groups treated with Padma 28, with no significant change in the placebo group. In general, the studies presented results comparing the treatment arms before and after treatment but made no comparisons between the Padma 28 and placebo groups. Pooled data of maximum walking distance after treatment with Padma 28 and placebo from two studies indicated a statistically significant difference in maximum walking distance (mean difference (MD) 95.97 m, 95% confidence interval (CI) 79.07 m to 112.88 m, P < 0.00001). The clinical importance of these observed changes in walking distance is unclear as no quality of life data were reported. There was no effect on ankle brachial index. Mild side effects, especially gastrointestinal discomfort, tiredness and skin eruption, were reported but this outcome was not statistically significantly different between the groups (odds ratio (OR) 1.09, 95% CI 0.42 to 2.83, P = 0.86). AUTHORS' CONCLUSIONS: Some evidence exists from individual trials to suggest that Padma 28 may be effective in increasing walking distances, at least in the short term (four months), in people with intermittent claudication. Side effects do not appear to be a problem. However, the longer term effects of treatment are unknown and the clinical significance of the improvements in walking distance are questionable. Moreover, the quality of the evidence is limited by the small sample size of the available trials, lack of detail on key elements required to assess sources of bias, such as around randomisation and blinding, limited reporting of statistical analyses that compared treatment groups, and relatively high withdrawal rates that were linked to the outcome that is patients were withdrawn if they failed to improve walking distance. There was also evidence of publication bias. We therefore feel there is currently insufficient evidence to support the use of Padma 28 in the routine management of intermittent claudication. Further well-designed research would be required to determine the true effects of this herbal preparation.
Asunto(s)
Claudicación Intermitente/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Caminata , Humanos , Efecto Placebo , Extractos Vegetales/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
Loss-of-function mutations in the CYP24A1 protein-coding region causing reduced 25 hydroxyvitamin D (25OHD) and 1,25 dihydroxyvitamin D (1,25(OH)2 D) catabolism have been observed in some cases of infantile hypercalcemia type 1 (HCINF1), which can manifest as nephrocalcinosis, hypercalcemia and adult-onset hypercalciuria, and renal stone formation. Some cases present with apparent CYP24A1 phenotypes but do not exhibit pathogenic mutations. Here, we assessed the molecular mechanisms driving apparent HCINF1 where there was a lack of CYP24A1 mutation. We obtained blood samples from 47 patients with either a single abnormality of no obvious cause or a combination of hypercalcemia, hypercalciuria, and nephrolithiasis as part of our metabolic and stone clinics. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine serum vitamin D metabolites and direct sequencing to confirm CYP24A1 genotype. Six patients presented with profiles characteristic of altered CYP24A1 function but lacked protein-coding mutations in CYP24A1. Analysis upstream and downstream of the coding sequence showed single nucleotide variants (SNVs) in the CYP24A1 3' untranslated region (UTR). Bioinformatics approaches revealed that these 3' UTR abnormalities did not result in microRNA silencing but altered the CYP24A1 messenger RNA (mRNA) secondary structure, which negatively impacted translation. Our experiments showed that mRNA misfolding driven by these 3' UTR sequence-dependent structural elements was associated with normal 25OHD but abnormal 1,25(OH)2 D catabolism. Using CRISPR-Cas9 gene editing, we developed an in vitro mutant model for future CYP24A1 studies. Our results form a basis for future studies investigating structure-function relationships and novel CYP24A1 mutations producing a semifunctional protein. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Regiones no Traducidas 3' , Hipercalcemia , Vitamina D3 24-Hidroxilasa , Humanos , Regiones no Traducidas 3'/genética , Cromatografía Liquida , Hipercalcemia/genética , Hipercalciuria/genética , Mutación/genética , Espectrometría de Masas en Tándem , Vitamina D , Vitamina D3 24-Hidroxilasa/genéticaRESUMEN
BACKGROUND: Optimal target blood pressure to reduce adverse cardiac remodelling in children with chronic kidney disease is uncertain. We hypothesised that lower blood pressure would reduce adverse cardiac remodelling. METHODS: HOT-KID, a parallel-group, open-label, multicentre, randomised, controlled trial, was done in 14 clinical centres across England and Scotland. We included children aged 2-15 years with stage 1-4 chronic kidney disease-ie, an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1·73 m2-and who could be followed up for 2 years. Children on antihypertensive medication were eligible as long as it could be changed to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) if they were not already receiving these therapies. Participants were randomly assigned (1:1) to standard treatment (auscultatory office systolic blood pressure target between the 50th and 75th percentiles) or intensive treatment (systolic target <40th percentile) by the chief investigator using a rapid, secure, web-based randomisation system. ACE inhibitors or ARBs were used as first-line agents, with the dose titrated every 2-4 weeks to achieve the target blood pressure levels. The primary outcome was mean annual difference in left ventricular mass index (LVMI) by echocardiography measured by a masked observer and was assessed in the intention-to-treat population, defined as all the children who underwent randomisation irrespective of the blood pressure reached. Secondary and safety outcomes were the differences between groups in mean left ventricular relative wall thickness, renal function, and adverse effects and were also assessed in the intention-to-treat population. This trial is registered with ISRCTN, ISRCTN25006406. FINDINGS: Between Oct 30, 2012, and Jan 5, 2017, 64 participants were randomly assigned to the intensive treatment group and 60 to the standard treatment group (median age of participants was 10·0 years [IQR 6·8-12·6], 69 [56%] were male and 107 [86%] were of white ethnicity). Median follow-up was 38·7 months (IQR 28·1-52·2). Blood pressure was lower in the intensive treatment group compared with standard treatment group (mean systolic pressure lower by 4 mm Hg, p=0·0012) but in both groups was close to the 50th percentile. The mean annual reduction in LVMI was similar for intensive and standard treatments (-1·9 g/m2·7 [95% CI -2·4 to -1·3] vs -1·2 g/m2·7 [-1·5 to 0·8], with a treatment effect of -0·7 g/m2·7 [95% CI -1·9 to 2·6] per year; p=0·76) and mean value in both groups at the end of follow-up within the normal range. At baseline, elevated relative wall thickness was more marked than increased LVMI and a reduction in relative wall thickness was greater for the intensive treatment group than for the standard treatment group (-0·010 [95% CI 0·015 to -0·006] vs -0·004 [-0·008 to 0·001], treatment effect -0·020 [95% CI -0·039 to -0·009] per year, p=0·0019). Six (5%) participants reached end-stage kidney disease (ie, an eGFR of <15 mL/min per 1·73 m2; three in each group) during the course of the study. The risk difference between treatment groups was 0·02 (95% CI -0·15 to 0·19, p=0·82) for overall adverse events and 0·07 (-0·05 to 0·19, p=0·25) for serious adverse events. Intensive treatment was not associated with worse renal outcomes or greater adverse effects than standard treatment. INTERPRETATION: These results suggest that cardiac remodelling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass. FUNDING: British Heart Foundation.
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Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Renal Crónica , Masculino , Niño , Humanos , Femenino , Presión Sanguínea , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Remodelación Ventricular , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
BACKGROUND: The British Association for Paediatric Nephrology Registry was established to analyse data related to renal replacement therapy (RRT) for children. The registry receives data from the 13 paediatric nephrology centres in the UK. AIM: To provide centre specific data so that individual centres can reflect on the contribution that their data makes to the national picture and to determine the extent to which their patient parameters meet nationally agreed audit standards for the management of children with established renal failure. METHOD: Data returns have been a mixture of electronic and paper returns. Data were analysed to calculate summary statistics and where applicable the percentage achieving an audit standard. The standards used were those set out by the Renal Association and the National Institute for Health and Clinical Excellence. RESULTS: Anthropometric data confirmed that children receiving RRT are short compared to healthy peers. Amongst patients with a height z-score of <2SD between 2000 and 2010, 27% were receiving growth hormone if they were on dialysis compared to 10% if they had a functioning transplant. Blood pressure was higher in children receiving RRT than in healthy children with wide inter-centre variation. The percentage of patients achieving the treatment standards for haemoglobin and ferritin has gradually increased over the last decade, more noticeably in dialysis patients. Analysis by age showed that the proportion of children with a haemoglobin below the standard was greatest for the under 5 years age group irrespective of RRT modality. The control of renal bone disease remained challenging. CONCLUSIONS: Optimizing growth in children on RRT remains challenging and the control of bone biochemistry in children on dialysis is imperfect. However there is some room for optimism as this year's data shows an improving trend in the control of anaemia and systolic blood pressure.
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Fallo Renal Crónico/terapia , Sistema de Registros/estadística & datos numéricos , Terapia de Reemplazo Renal/estadística & datos numéricos , Adolescente , Anemia/sangre , Anemia/etiología , Anemia/prevención & control , Antropometría , Presión Sanguínea , Calcio/sangre , Áreas de Influencia de Salud , Niño , Preescolar , Registros Electrónicos de Salud , Femenino , Ferritinas/sangre , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/prevención & control , Adhesión a Directriz , Unidades de Hemodiálisis en Hospital/estadística & datos numéricos , Hemoglobinas/análisis , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Hipertensión/etiología , Hipertensión/prevención & control , Lactante , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/fisiopatología , Masculino , Fosfatos/sangre , Guías de Práctica Clínica como Asunto , Terapia de Reemplazo Renal/normas , Centros de Atención Terciaria/estadística & datos numéricos , Reino Unido/epidemiologíaRESUMEN
AIMS: To describe the demographics of the paediatric RRT population under the age of 16 years in the UK and to analyse changes in demography with time. METHODS: Data were collected from all 13 paediatric renal centres within the UK. A series of cross-sectional and longitudinal analyses were performed to describe the demographics of prevalent paediatric RRT patients. RESULTS: A total of 870 children and young people under 18 with ERF were receiving treatment at paediatric nephrology centres in 2010. At the census date, 76.7% had a functioning transplant, 14.3% were receiving peritoneal dialysis (PD) and 9.0% were receiving haemodialysis (HD). In patients aged <16 years the prevalence of ERF was 59.3 pmarp and the incidence 8.1 pmarp. Analysis of trends over the last 15 years shows that both incidence and prevalence are increasing with the most marked increases in children aged 12-16 years and in ethnic minority groups. A third of the patients have one or more reported comorbidities. At transfer to adult services, 84.9% of patients had a functioning renal transplant. CONCLUSIONS: The data provided in this report show increasing trends over 15 years in the incidence and prevalence of established renal failure. This is important for the planning of the provision of care for children needing renal replacement therapy. The inclusion this year of an analysis of the patients transferring to adult services may assist in developing care pathways for this vulnerable group.
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Sistema de Registros/estadística & datos numéricos , Terapia de Reemplazo Renal/estadística & datos numéricos , Adolescente , Distribución por Edad , Áreas de Influencia de Salud , Niño , Preescolar , Comorbilidad , Estudios Transversales , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/terapia , Etnicidad/estadística & datos numéricos , Femenino , Tasa de Filtración Glomerular , Unidades de Hemodiálisis en Hospital/estadística & datos numéricos , Humanos , Incidencia , Lactante , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Trasplante de Riñón/estadística & datos numéricos , Estudios Longitudinales , Masculino , Morbilidad/tendencias , Prevalencia , Distribución por Sexo , Centros de Atención Terciaria/estadística & datos numéricos , Reino Unido/epidemiologíaRESUMEN
IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection-related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, -0.02; 95% CI, -0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39.
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Síndrome Nefrótico , Infecciones del Sistema Respiratorio , Corticoesteroides/uso terapéutico , Niño , Humanos , Masculino , Síndrome Nefrótico/complicaciones , Síndrome Nefrótico/tratamiento farmacológico , Prednisolona/uso terapéutico , Calidad de Vida , Recurrencia , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/prevención & controlRESUMEN
BACKGROUND: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5-7 days during an upper respiratory tract infection reduces the risk of relapse. OBJECTIVES: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. DESIGN: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. SETTING: A total of 122 UK paediatric departments, of which 91 recruited patients. PARTICIPANTS: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. MAIN OUTCOME MEASURES: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. RESULTS: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference -0.024, 95% confidence interval -0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. LIMITATIONS: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. CONCLUSIONS: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. FUTURE WORK: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 3. See the NIHR Journals Library website for further project information.
Steroid-sensitive nephrotic syndrome is a kidney condition in which protein leaks into the urine, causing generalised swelling. In most children, the condition recurs or relapses. Relapses often occur following an upper respiratory tract infection (i.e. a cough, cold or sore throat). Research in tropical countries suggests that if children have a small dose of daily steroids for a week at the time of an upper respiratory tract infection then they are less likely to relapse. The selection of children for these studies and the different patterns of infection mean that we are not certain if this treatment would work in the UK. A total of 365 children with relapsing nephrotic syndrome took part. Half of the children took a steroid and the other half took dummy tablets (placebo) for 6 days at the start of an upper respiratory tract infection. We followed up the children for 12 months and collected information on relapses and other treatments and information from questionnaires about behaviour and quality of life. We also investigated whether or not there were cost savings with this treatment. There were 271 children who had an upper respiratory tract infection in the 12 months of the study and so only these children were included in the analyses. Giving 6 days of a low-dose steroid at the time of an upper respiratory tract infection did not reduce the risk of a relapse. There was also no effect on the overall number of relapses, the number of children needing to start extra preventative treatments or side effects of steroids. Although there was no clinical effect, the economic evaluation found that giving prednisolone led to lower treatment costs overall and higher quality of life and might, therefore, offer better value for money, but this has to be interpreted against the clinical evidence of no significant effect. Our conclusion is that there is no clinical benefit to giving children low-dose prednisolone at the time of an upper respiratory tract infection.
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Síndrome Nefrótico , Infecciones del Sistema Respiratorio , Niño , Preescolar , Análisis Costo-Beneficio , Humanos , Recurrencia Local de Neoplasia , Síndrome Nefrótico/tratamiento farmacológico , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Calidad de Vida , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
BACKGROUND: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. OBJECTIVE: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. METHODS: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. RESULTS: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. CONCLUSION: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.