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Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. Methods: In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. Results: The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Conclusion: Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.
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OBJECTIVE: IgA vasculitis (IgAV) (formerly Henoch-Schönlein Purpura, HSP) rarely causes severe skin lesions in children. The purpose of the research was to determine whether severe skin manifestations were associated with a more severe disease course. METHODS: Severe cutaneous manifestations were defined as presence of hemorrhagic vesicles, bullae, ulcerations and/or necroses. Data were collected retrospectively from 12 international tertiary university medical centers. RESULTS: A total of 64 patients with the most severe skin changes in IgAV/HSP and median (Q1, Q3) age of 8.08 (5.08, 11.92) years at the disease onset were compared with 596 IgAV/HSP patients without these manfiestations and median (Q1, Q3) age of 6.33 (4.50, 8.92) years. The patients with severe cutaneous manifestations were older in comparison to other patients with IgAV/HSP (p<0.001), they developed nephritis more frequently (40.6% vs. 20.6%, p = 0.001) with worse outcome of renal disease (p = 0.001). This group of patients also had higher frequencies of severe gastrointestinal complications like hematochezia, massive bleeding and/or intussusception (29.3% vs. 14.8%, p<0.001). d-dimer concentrations were significantly higher in these patients (4.60 mg/L vs. 2.72 mg/L, p = 0.003) and they had more frequent need for treatment with systemic glucocorticoids (84.4% vs. 37.2%, p<0.001) in comparison with the control group. Further multivariate analysis showed that severe cutaneous changes were associated with higher risk of developing nephritis [OR=3.1 (95%CI 1.04-9.21), p = 0.042] and severe gastrointestinal complications [OR=3.65 (95%CI 1.08-12.37), p = 0.038]. CONCLUSION: Patients with IgAV/HSP and severe skin manifestations had a more severe clinical course and more frequently required glucocorticoids compared to classic IgAV/HSP patients.
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Enfermedades Gastrointestinales , Vasculitis por IgA , Nefritis , Humanos , Niño , Vasculitis por IgA/complicaciones , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/patología , Estudios Retrospectivos , Glucocorticoides/uso terapéutico , Nefritis/complicaciones , Nefritis/tratamiento farmacológico , Enfermedades Gastrointestinales/tratamiento farmacológico , Resultado del Tratamiento , Inmunoglobulina A/uso terapéuticoRESUMEN
BACKGROUND: Only a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU. METHODS: All patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively. RESULTS: Fifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8-16.9) years and median follow-up time was 5.7 (1.1-21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 µmol/l (47-1,016) and that of eGFR 47 ml/min/1.73m2 (8-124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2 (median 83; 61-89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted. CONCLUSIONS: Our study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Nefritis Intersticial , Uveítis , Adolescente , Biopsia , Niño , Preescolar , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Lactante , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/epidemiología , Nefritis Intersticial/patología , Estudios Retrospectivos , Resultado del Tratamiento , Uveítis/tratamiento farmacológico , Uveítis/epidemiología , Uveítis/patologíaRESUMEN
OBJECTIVES: To describe school performance in pediatric intensive care survivors, as well as the influence of chronic diseases, psychological well-being, and family socioeconomic status on poor school performance. DESIGN: Register-based observational descriptive follow-up study. SETTING: A multicenter national study. PATIENTS: All pediatric patients who were admitted to an ICU in Finland in 2009-2010. Children and adolescents of or beyond school age. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Questionnaires regarding the child's coping in school classes, chronic illnesses, as well as family socioeconomic factors were sent to every child alive 6 years after discharge from intensive care in Finland. Mental well-being was measured with the Strengths and Difficulties Questionnaire. There were 1,109 responders in an ICU group of 3,674 children. Seven-hundred fifty-three of the respondents were of school age or older. Of these, 13% (101/753) demonstrated poor school performance. Children with difficulties in school more often had a need for regular medication (71.3% vs 32.4%; p < 0.001), healthcare visits (91.1% vs 80.6%; p = 0.01), some regular therapy (60.4% vs 13.7%; p < 0.001), chronic illnesses (86.3% vs 48.4%; p < 0.001), or additional ICU admissions (36.5% vs 14.9%; p = 0.003). Schooling difficulties were reported more often in children with abnormal Strengths and Difficulties Questionnaire scores compared to those with normal or borderline scores (24.8% vs 5.4%; p < 0.001). In an adjusted logistic regression model, which included age, number of chronic diseases, and need for therapy, poor school performance was predicted by abnormal Strengths and Difficulties Questionnaire scores, nonacademic parental education, and paternal manual labor status. CONCLUSIONS: Difficulties in school were more frequent when the child had chronic comorbid illnesses, especially neurologic or chromosomal abnormalities, had poor mental health, father was employed in manual labor, or parents were uneducated.
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Salud Mental , Clase Social , Adolescente , Niño , Enfermedad Crónica , Cuidados Críticos , Finlandia/epidemiología , Estudios de Seguimiento , Humanos , Instituciones AcadémicasRESUMEN
BACKGROUND: Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome. METHODS: The data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis. RESULTS: Fifty-eight out of 262 culture-positive cases developed verified (n = 58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n = 37, 66%). Age under 3 years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0 years of follow-up. Age under 3 years, leukocyte count over 20 × 109/L, and need for dialysis were predictive factors for poor renal outcome. CONCLUSIONS: Age under 3 years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.
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Síndrome Hemolítico-Urémico/epidemiología , Adolescente , Factores de Edad , Niño , Preescolar , Creatinina/sangre , Femenino , Síndrome Hemolítico-Urémico/microbiología , Síndrome Hemolítico-Urémico/terapia , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Diálisis Renal/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Escherichia coli Shiga-Toxigénica/aislamiento & purificaciónRESUMEN
Blood myxovirus resistance protein A (MxA) has broad antiviral activity, and it is a potential biomarker for symptomatic virus infections. Limited data is available of MxA in coinciding viral and bacterial infections. We investigated blood MxA levels in children hospitalized with a febrile urinary tract infection (UTI) with or without simultaneous respiratory virus infection. We conducted a prospective observational study of 43 children hospitalized with febrile UTI. Nasopharyngeal swab samples were collected at admission and tested for 16 respiratory viruses by nucleic acid detection methods. Respiratory symptoms were recorded, and blood MxA levels were determined. The median age of study children was 4 months (interquartile range, 2-14 months). A respiratory virus was detected in 17 (40%) children with febrile UTI. Of the virus-positive children with febrile UTI, 7 (41%) had simultaneous respiratory symptoms. Blood MxA levels were higher in virus-positive children with respiratory symptoms (median, 778 [interquartile range, 535-2538] µg/L) compared to either virus-negative (155 [94-301] µg/L, P < 0.001) or virus-positive (171 [112-331] µg/L, P = 0.006) children without respiratory symptoms at presentation with febrile UTI. MxA differentiated virus-positive children with respiratory symptoms from virus-negative without symptoms by an area under the receiver operating characteristic curve of 0.96. Respiratory viruses were frequently detected in children with febrile UTI. In UTI with simultaneous respiratory symptoms, host antiviral immune response was demonstrated by elevated blood MxA protein levels. MxA protein could be a robust biomarker of symptomatic viral infection in children with febrile UTI.
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Proteínas de Resistencia a Mixovirus/sangre , Infecciones del Sistema Respiratorio/sangre , Infecciones del Sistema Respiratorio/epidemiología , Infecciones Urinarias/epidemiología , Infecciones Urinarias/virología , Biomarcadores/sangre , Femenino , Fiebre , Humanos , Lactante , Masculino , Prevalencia , Estudios Prospectivos , Curva ROC , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Infecciones Urinarias/microbiología , Infecciones Urinarias/patologíaRESUMEN
OBJECTIVES: We investigated the long-term psychologic symptoms of patients who survived pediatric intensive care admission. DESIGN: Longitudinal follow-up study. SETTING: Nationwide cohort study based on a national ICU register and a questionnaire survey. PATIENTS: All pediatric patients (0-16 yr old) who were admitted to an ICU in Finland in 2009-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six years after ICU admission, all surviving patients were sent the Strengths and Difficulties Questionnaire, and questionnaires regarding chronic diseases and need for medication and therapy. At the end of the follow-up period, there were 3,674 surviving children who had been admitted to an ICU in 2009-2010. Of these children, 1,105 completed the Strengths and Difficulties Questionnaire 6 years after admission. Strengths and Difficulties Questionnaire scores were abnormal for 84 children (7.6%), borderline for 80 (7.2%), and normal for 941 (85.2%). Participants with abnormal scores were younger at admission to the ICU (3.06 vs 4.70 yr; p = 0.02), and more commonly had a chronic disease (79.5% vs 47.4%; p < 0.001), a need for continuous medication (49.4% vs 31.7%; p < 0.001), a need for therapy (58.5% vs 15.9%; p < 0.001), and a need for annual healthcare visits (91.4% vs 85.2%; p = 0.05). Abnormal Strengths and Difficulties Questionnaire scores were associated with higher rates of neurologic (32.1% vs 10.2%), gastrointestinal (7.1% vs 3.9%), psychiatric (3.6% vs 0.5%), and chromosomal disorders (9.5% vs 1.3%), as well as with long-term pain (1.2% vs 0.6%). CONCLUSIONS: Participants with abnormal Strengths and Difficulties Questionnaire scores (poor psychologic outcome) at 6 years after childhood ICU admission more commonly suffered neurologic, chromosomal, or psychiatric diagnoses or long-term pain, and generally required higher levels of healthcare services, therapies, and medication.
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Niño Hospitalizado/psicología , Cuidados Críticos/psicología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Sobrevivientes/psicología , Adolescente , Niño , Preescolar , Enfermedad Crónica/psicología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Optimal treatment of Henoch-Schönlein purpura nephritis (HSN) remains unclear. We evaluated outcome of pediatric HSN patients treated initially with either methylprednisolone (MP) or cyclosporine A (CyA) in Finland between 1996 and 2011. METHODS: Outcome of 62 HSN patients was evaluated by screening urine and blood samples (n = 51) or by collecting clinical parameters from medical charts until last follow-up visit (n = 11). Sixty (97%) patients had nephrotic-range proteinuria and/or ISKDC grade ≥ III before initial treatment. Patients were initially treated with either MP pulses (n = 42) followed by oral prednisone or with CyA (n = 20). Fifty-nine (95%) patients received angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. RESULTS: Mean follow-up time was 10.8 years (range 3.2-21.2 years). One patient developed end-stage renal disease and another had decreased renal function (eGFR < 60 mL/min/1.73m2), both initially treated with MP (3%). Six patients (5 MP, 1 CyA) had eGFR between 60 and 89 mL/min/1.73m2 (10%). Eighteen patients (13 MP, 5 CyA) had proteinuria and/or hematuria (29%) and four of them had proteinuria > 0.5 g/day at end of follow-up. Sixteen (38%) MP-treated and two (10%) CyA-treated patients needed additional immunosuppressive treatment (RR 3.81, 95% CI 1.16-14.3, p = 0.035). Late initiation of treatment was associated with an increased risk for persistent proteinuria. CONCLUSIONS: Long-term outcome was relatively good in both treatment groups. However, since urinary abnormalities may persist or develop, long-term follow-up of HSN patients is mandatory. Early initiation of treatment had a favorable effect on proteinuria.
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Ciclosporina/uso terapéutico , Glomerulonefritis/tratamiento farmacológico , Vasculitis por IgA/complicaciones , Inmunosupresores/uso terapéutico , Metilprednisolona/uso terapéutico , Adolescente , Niño , Femenino , Finlandia/epidemiología , Estudios de Seguimiento , Tasa de Filtración Glomerular , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Humanos , Vasculitis por IgA/tratamiento farmacológico , Vasculitis por IgA/inmunología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/prevención & control , Glomérulos Renales/irrigación sanguínea , Glomérulos Renales/patología , Masculino , Proteinuria/epidemiología , Proteinuria/etiología , Proteinuria/prevención & control , Estudios Retrospectivos , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoAsunto(s)
Dinaminas/genética , Músculo Esquelético/patología , Mutación/genética , Miopatías Estructurales Congénitas/genética , Miopatías Estructurales Congénitas/patología , Dinamina II , Femenino , Humanos , Lactante , Masculino , Modelos Moleculares , Fenotipo , Proteínas Tirosina Fosfatasas no Receptoras/genéticaRESUMEN
PURPOSE: Long-term data are urgently needed in children after intensive care. The aim of this study was to measure health-related quality of life 6 years after intensive care in a paediatric intensive care population. METHODS: This national, multicentre study enrolled all children and young people admitted to intensive care units (ICUs) in Finland in 2009 and 2010. The data concerning ICU stay were collected retrospectively from the ICU data registries and combined with prospective data from Paediatric Quality of Life Inventory (PedsQL 4.0) questionnaires, the generic 15D, 16D or 17D instrument, and data regarding children's chronic diagnoses and need for healthcare support. RESULTS: The questionnaires were answered by 1109 of 3682 living children and adolescents admitted to an ICU, response rate was 30.1%. Among the responders, 90 children (8.4%) had poor (under - 2 SD) PedsQL scores. Children with low scores had a higher rate of chronic diagnoses (94.4% vs. 47.6%), medication on a daily basis (78.7% vs. 29.4%) and a greater need for healthcare services (97.7% vs. 82.2%) than those with normal scores. Diagnoses associated with poor quality of life were asthma, epilepsy, cerebral palsy and other neurological diseases, chromosomal alterations, cancer and long-term pain. These children were mostly admitted electively, and less frequently on an emergency basis, but no other significant differences were found during the intensive care stay. CONCLUSIONS: The long-term quality of life after paediatric intensive care is good for the majority of children and young people, and it is dependent on the number of chronic diagnoses and the burden of the chronic disease, especially neurological diseases.
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Cuidados Críticos , Enfermedad Crítica/psicología , Estado de Salud , Calidad de Vida , Adolescente , Distribución por Edad , Niño , Preescolar , Enfermedad Crítica/epidemiología , Enfermedad Crítica/terapia , Femenino , Finlandia/epidemiología , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Estudios Longitudinales , Masculino , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenAsunto(s)
Fluidoterapia/métodos , Glucosa/administración & dosificación , Hiponatremia/prevención & control , Adolescente , Niño , Preescolar , Fluidoterapia/efectos adversos , Gluconatos/administración & dosificación , Humanos , Hiponatremia/etiología , Lactante , Soluciones Isotónicas , Cloruro de Magnesio/administración & dosificación , Cloruro de Potasio/administración & dosificación , Acetato de Sodio/administración & dosificación , Cloruro de Sodio/administración & dosificaciónRESUMEN
BACKGROUND: Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3+ T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. METHODS: A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4+, FOXP3+ and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. RESULTS: FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3+ cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4+ staining was successful in 23 patients. The density of all lymphocytes (CD4+, CD4+FOXP3+ and FOXP3+ cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. CONCLUSIONS: FOXP3+ T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3+ T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.
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Nefritis Intersticial/inmunología , Linfocitos T Reguladores/inmunología , Uveítis/inmunología , Adolescente , Biopsia , Niño , Femenino , Factores de Transcripción Forkhead/inmunología , Humanos , MasculinoRESUMEN
OBJECTIVES: The aim of the study was to compare long-term mortality and causes of death in children post admission to an ICU with a control population of same age. DESIGN: Longitudinal follow-up study. SETTING: Registry study of a national ICU register and hospital registries. PATIENTS: Children admitted to an ICU in the years 2009 and 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mortality and causes of death following ICU discharge were analyzed retrospectively. The median follow-up period was 4.9 years (25-75th percentiles, 4.4-5.5 yr). The causes of death in survivors 30 days after ICU discharge were compared with a cohort of 1 million children of the general population of same age. In total, 2,792 children were admitted to an ICU during the study period. Of those, 53 (1.9%) died in the ICU and 2,739 were discharged. Thirteen children died within 30 days of discharge, and 68 died between 30 days and the end of follow-up (December 31, 2014). In the control population (n = 1,020,407 children), there were 1,037 deaths (0.10%) from 2009 to 2014. The standardized mortality rate for the children admitted to the ICU during the study period was 53.4 (95% CI, 44.7-63.2). The standardized mortality rate for those children alive 1 year after discharge was 16.7 (12.1-22.6). One-year cumulative mortality was 3.3%. The most common causes of death in subjects alive 30 days post ICU were cancer (35.3%), neurologic (17.6%), and metabolic diseases (11.7%), whereas trauma was the most common cause in the control group (45.3%). CONCLUSIONS: There was an increased risk of death in a cohort of ICU-admitted children even 3 years after discharge. In those who survived 30 days after discharge, medical causes of death were dominant, whereas deaths due to trauma were most common in the control group.
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Causas de Muerte , Mortalidad del Niño , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Finlandia , Estudios de Seguimiento , Hospitales Pediátricos/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Alta del Paciente/estadística & datos numéricos , Sistema de Registros , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a common cause of end-stage renal disease in children but also occurs as an adult-onset condition. In a subset of SRNS patients, pathogenic variants are found in genes coding for podocyte foot process proteins. The aim of this study was to define the role of pathogenic variants in Finnish patients with familial and sporadic SRNS. METHODS: We analyzed SRNS-related genes NPHS1, NPHS2, NEPH1, ACTN4, TRPC6, INF2, WT1, CD2AP, LAMB2, and PLCE1 for disease-causing variants using direct sequencing of exons and intron/exon boundaries in all members of a family with dominant SRNS with early onset and slow progression to end-stage renal disease. We carried out a whole genome sequencing in two affected and two healthy family members. The function of found podocin variant was studied using co-immunoprecipitation and immunohistochemistry. Podocyte gene sequences were analyzed in a cohort of Finnish non-familial SRNS patients. RESULTS: A heterozygous de novo deletion, c.988_989delCT in NPHS2, was found in all affected family members and in none of their healthy relatives, non-familial patients or controls. No other SRNS-related gene variant, coding or non-coding co-segregated with the disease phenotype in the family. While the truncated podocin remained able to bind nephrin, the expression of nephrin was fragmented and podocin expression reduced. The gene analysis of the non-familial SRNS patients revealed few variants. CONCLUSION: The role of podocin variants in nephrotic syndrome may be more varied than previously thought.
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Resistencia a Medicamentos/genética , Genes Dominantes , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Síndrome Nefrótico/genética , Eliminación de Secuencia , Esteroides/uso terapéutico , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , Progresión de la Enfermedad , Finlandia , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia , Heterocigoto , Humanos , Lactante , Recién Nacido , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/genética , Fallo Renal Crónico/terapia , Trasplante de Riñón , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/terapia , Linaje , Fenotipo , Diálisis Renal , Factores de Tiempo , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
OBJECTIVES: To investigate the association between the type of ICU and mortality for children treated at PICUs and adult ICUs. DESIGN: This was a national multicenter cohort study. Data were collected from electronic critical care data management systems at 3 units and from national intensive care registries at 26 units. SETTING: We assessed the incidence of admissions, length of stay at ICUs, main diagnoses, and mortality for children at ICUs. Units were categorized as PICUs or as adult ICUs located at university hospitals or at non-academic central hospitals. PATIENTS: Children younger than 17 years of age treated at ICUs in Finland. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: There were 4,876 admissions from 2009 to 2010, and 98.9% of patients survived until unit discharge. The mean length of stay was 3.0 ± 7.4 days; 1,395 patients (35%) required mechanical ventilation at PICUs versus 167 (35%) at adult university hospital ICUs versus 79 (19%) at central hospital ICUs (p < 0.001). The odds for mortality in univariate regression analysis were emergency admission (odds ratio, 3.99; 95% CI, 1.82-8.76), cardiovascular (odds ratio, 7.84; 95% CI, 3.49-22.88), gastrointestinal (odds ratio, 5.37; 95% CI, 1.45-19.88), acute infections (odds ratio, 2.83; 95% CI, 1.23-6.48), hematologic/oncologic disease (odds ratio, 10.32; 95% CI, 3.14-33.86), and nonsurgical trauma (odds ratio, 3.53; 95% CI, 1.19-10.41). Treatment at adult ICUs had higher odds of mortality compared with PICUs (university hospital: odds ratio, 3.93; 95% CI, 1.85-8.35 and central hospital: odds ratio, 3.91; 95% CI, 1.69-9.05), adjusted for readmission less than 48 hours after discharge, emergency admission, mechanical ventilation, and diagnostic group. CONCLUSIONS: Pediatric patients treated at PICUs showed lower mortality. Requirement of mechanical ventilation, emergency admission, and readmission less than 48 hours after discharge and cardiovascular, gastrointestinal, acute infections, hematologic/oncologic disease, and nonsurgical trauma were associated with higher risk of mortality.
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Mortalidad del Niño , Mortalidad Hospitalaria , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Finlandia/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Lactante , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Masculino , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Autoimmune tubulo-interstitial nephritis (TIN) is a rare complication of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Previous data on TIN and other renal or urologic manifestations of APECED are sparse. METHODS: We performed a retrospective study on the urinary and renal tract diseases in a cohort of 30 Finnish patients with APECED (mean age 40 years), with special emphasis on the clinical presentation and the immunologic characteristics of TIN. Clinical and laboratory findings, specific anticytokine and kidney-specific antibodies were analysed. RESULTS: Five of the 30 (17%) patients had moderate-to-severe renal failure, including 3 (10%) with TIN, leading to either transplantation, haemodialysis or immunosuppressive treatment. No other cause other than APECED was found for the TIN. All three patients with TIN had circulating antibodies against the distal part of the nephron, as did 30% of all cohort cases. Two had nephrocalcinosis, and two had renal tubular acidosis type 1. Immunosuppressive therapy with mycophenolate mofetil or rituximab in one pediatric case did not revert the TIN, however. CONCLUSIONS: Renal failure should raise concern for TIN in APECED. It discloses some specific features: no uveitis, no glycosuria and inconstant urinalysis anomalies. Regular renal monitoring for any APECED patient should be performed. Circulating antibodies against the distal part of the nephron are frequent and present in all TIN patients, but their pathologic significance is not yet known. Future studies will be needed to understand the triggers leading to overt clinical disease in these patients.
Asunto(s)
Nefritis Intersticial/etiología , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/fisiopatología , Adolescente , Adulto , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Niño , Creatinina/sangre , Femenino , Finlandia , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/tratamiento farmacológico , Estudios Retrospectivos , Rituximab , Adulto JovenRESUMEN
Acute idiopathic tubulointerstitial nephritis (TIN) is considered a condition with a good long-term prognosis. However, there is evidence that some patients develop permanent renal impairment. The aim of this study was to evaluate the clinical characteristics of TIN at the time of diagnosis in children and determine whether the findings upon presentation predict renal outcome. The clinical data and biopsy findings from 26 children with idiopathic TIN admitted to four Finnish university hospitals were analyzed retrospectively. Twenty-five patients (96%) manifested renal insufficiency. After the mean follow-up time of 2.75 years (SD 2.5; 0.9-13.5), 4 patients (15%) had permanent renal insufficiency and 8 patients (31%) had persistent low-molecular weight proteinuria. Uveitis was found in 12 patients (46%). Four of these patients (33%) developed chronic uveitis. Our analysis showed that none of the laboratory or biopsy findings upon presentation prognosticated renal outcome. No correlation between renal disease and uveitis could be found either. The occurrence of uveitis among TIN patients was higher than previously reported. Uveitis may develop late and without recurrence of renal dysfunction. Therefore, follow-up by a pediatrician and by an ophthalmologist is warranted in children with acute TIN for at least 12 months from diagnosis.