RESUMO
BACKGROUND: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Due to a lack of evidence, treatment recommendations are based on expert opinion, resulting in variation. The aim of this study was to describe the clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy-proven IgAVN in order to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy-proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analysed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow-up. RESULTS: The median follow-up was 3.7 years (interquartile range 2-6.2). At last follow-up, 29% of patients had an eGFR <90 mL/min/1.73 m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second-line immunosuppressive regimen being superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow-up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly, there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.
Assuntos
Taxa de Filtração Glomerular , Imunossupressores , Humanos , Masculino , Criança , Feminino , Estudos Retrospectivos , Adolescente , Imunossupressores/uso terapêutico , Pré-Escolar , Prognóstico , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Seguimentos , Terapia de Imunossupressão/métodos , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/complicações , Vasculite por IgA/diagnóstico , Resultado do Tratamento , Vasculite/tratamento farmacológicoRESUMO
BACKGROUND: Vitamin C is a potent scavenger of reactive oxygen species, which induce neutrophil extracellular trap (NET) formation. NETs are a major source of autoantigens and are involved in systemic lupus erythematosus (SLE) pathogenesis. We determined vitamin C status and evaluated NET formation and inflammatory cytokines in children with lupus nephritis. METHODS: Serum vitamin C was measured in 46 patients (82.6% females, mean age 14.5 ± 0.3 years). Vitamin C levels < 0.3 mg/dL indicated vitamin C deficiency. Patients were divided into two groups according to serum vitamin C levels: normal and low (< 0.3 mg/dL). We compared NET formation and levels of SLE-related cytokines, including interleukin (IL)-8, IL-10, and tumor necrosis factor-α (TNF-α), between groups. NET formation was determined through measurement of serum citrullinated histone 3 levels and mRNA expression of peptidyl arginine deiminase-4 and assessment of the percentage of neutrophils with NETs by immunofluorescence. RESULTS: Nine patients (19.6%) had vitamin C deficiency. Kidney pathology assessment at disease onset revealed that histological activity index and number of kidney biopsies containing crescentic glomeruli were higher in vitamin C-deficient patients, but chronicity index was not. NET formation and serum IL-8 were more prominent in vitamin C-deficient patients. Serum IL-8 levels were 12.9 ± 5.2 pg/mL in low vitamin C group and 5.2 ± 0.9 pg/mL in normal vitamin C group (p = 0.03). Serum IL-10 and TNF-α were similar between groups. CONCLUSIONS: Our study demonstrated correlation among vitamin C deficiency, increased NET formation, and IL-8 upregulation in children with lupus nephritis. A prospective study is required to evaluate causeâeffect relationships of vitamin C status, NET formation and IL-8 expression.
Assuntos
Deficiência de Ácido Ascórbico , Armadilhas Extracelulares , Interleucina-8 , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Adolescente , Criança , Feminino , Humanos , Masculino , Ácido Ascórbico , Deficiência de Ácido Ascórbico/complicações , Citocinas/metabolismo , Armadilhas Extracelulares/metabolismo , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Lupus nephritis (LN) is a very severe manifestation of lupus. There is no consensus on which treatment goals should be achieved to protect kidney function in children with LN. METHODS: We retrospectively analyzed trends of commonly used laboratory biomarkers of 428 patients (≤ 18 years old) with biopsy-proven LN class ≥ III. We compared data of patients who developed stable kidney remission from 6 to 24 months with those who did not. RESULTS: Twenty-five percent of patients maintained kidney stable remission while 75% did not. More patients with stable kidney remission showed normal hemoglobin and erythrocyte sedimentation rate from 6 to 24 months compared to the group without stable kidney remission. eGFR ≥ 90 ml/min/1.73m2 at onset predicted the development of stable kidney remission (93.8%) compared to 64.7% in those without stable remission (P < 0.00001). At diagnosis, 5.9% and 20.2% of the patients showed no proteinuria in the group with and without stable kidney remission, respectively (P = 0.0001). dsDNA antibodies decreased from onset of treatment mainly during the first 3 months in all groups, but more than 50% of all patients in both groups never normalized after 6 months. Complement C3 and C4 increased mainly in the first 3 months in all patients without any significant difference. CONCLUSIONS: Normal eGFR and the absence of proteinuria at onset were predictors of stable kidney remission. Significantly more children showed normal levels of Hb and erythrocyte sedimentation rate (ESR) from 6 to 24 months in the group with stable kidney remission.
Assuntos
Biomarcadores , Taxa de Filtração Glomerular , Nefrite Lúpica , Humanos , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Criança , Feminino , Masculino , Estudos Retrospectivos , Biomarcadores/sangue , Adolescente , Sedimentação Sanguínea , Indução de Remissão , Rim/patologia , Rim/fisiopatologia , Complemento C3/análise , Complemento C3/metabolismo , Anticorpos Antinucleares/sangue , Proteinúria/etiologia , Proteinúria/urina , Proteinúria/sangue , Proteinúria/diagnóstico , Complemento C4/análise , Complemento C4/metabolismo , Pré-EscolarRESUMO
BACKGROUND: Immumoglobulin A (IgA) vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is a self-limiting systemic vasculitis in children. Kidney involvement is associated with a long-term unfavorable outcome and can lead to significant morbidity. This study was conducted to describe the clinical and laboratory characteristics of childhood IgAV with kidney involvement and to identify risk factors associated with IgAV nephritis (IgAVN). METHODS: This was an ambidirectional descriptive study of 77 children with IgAV. All demographic data, clinical features, and laboratory tests were collected from electronic medical records from January 2010 to December 2022. Risk factors for kidney involvement in IgAV were assessed using multivariate logistic regression. Kaplan-Meier survival analysis was used to calculate the time to commencement of kidney involvement. RESULTS: Twenty-five children (32.4% of the IgAV patients) developed IgAVN. The common findings in IgAV with kidney involvement were microscopic hematuria (100%), nephrotic range proteinuria (44%), and non-nephrotic range proteinuria (40%). Multivariate logistic regression showed that age greater than 10 years (adjusted hazard ratio, AHR 4.66; 95% confidence interval, CI, 1.91-11.41; p = 0.001), obesity (body mass index, BMI, z-score ≥ +2 standard deviations, SDs) (AHR 3.59; 95% CI 1.41-9.17; p = 0.007), and hypertension at onset (AHR 4.78; 95% CI 1.76-12.95; p = 0.002) were associated significantly with kidney involvement. During follow up, most IgAV patients developed nephritis within the first 9 months. CONCLUSION: Age greater than 10 years, obesity, and hypertension at presentation were predictive factors for IgAVN. Our study emphasized that IgAV patients with risk factors should be closely monitored for at least 1 year after the onset of the disease.
Assuntos
Vasculite por IgA , Humanos , Masculino , Feminino , Criança , Fatores de Risco , Vasculite por IgA/complicações , Vasculite por IgA/epidemiologia , Vasculite por IgA/diagnóstico , Pré-Escolar , Adolescente , Estudos Retrospectivos , Proteinúria/etiologia , Proteinúria/epidemiologia , Estimativa de Kaplan-Meier , Hematúria/etiologia , Hematúria/epidemiologia , Modelos Logísticos , Rim/patologia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/epidemiologiaRESUMO
BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Nefrite Lúpica , Adolescente , Criança , Feminino , Humanos , Masculino , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Rim/patologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Ácido Micofenólico/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.
Assuntos
Falência Renal Crônica , Nefrite Lúpica , Adolescente , Biópsia , Criança , Feminino , Humanos , Rim/patologia , Nefrite Lúpica/patologia , Masculino , Indução de Remissão , Estudos RetrospectivosRESUMO
PURPOSE: Adolescents with systemic lupus erythematosus (SLE) are susceptible to sleep impairments. We aimed to determine the prevalence and factors related to sleep impairments, and the associations of sleep impairments with health-related quality of life (HRQOL) in Thai adolescents with SLE. METHODS: Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire for Adolescents (PHQA), and Pediatric Quality of Life Inventory™ 4.0 Core Scales were administered to 57 participants with SLE aged 13-18 years to evaluate sleep, depression, and HRQOL, respectively. Participants were divided into "good sleep" (PSQI scores <5) and "poor sleep" groups (PSQI scores ≥5). Participants with body mass index (BMI) >23 kg/m2 were classified into the high BMI group. FINDINGS: Eighteen participants (31.6%) were in the poor sleep group. High BMI and PHQA scores were associated with sleep impairments with the odds ratio of 8.00 (95% CI 1.50-42.64; p = 0.02), and 1.25 (95% CI 1.01-1.54; p = 0.04), respectively. In terms of HRQOL, adolescents with SLE had the highest scores in social functioning and the lowest scores in school functioning. Good sleepers had better scores than poor sleepers across all sub-categories except for social functioning, and the difference was significant in emotional functioning (90% (IQR 75-100) vs. 70% (IQR 55-85); p = 0.03). CONCLUSIONS: A substantial number of adolescents with SLE had sleep impairments, which decreased HRQOL, particularly in emotional functioning. Sleep impairments were associated with obesity and depression. IMPLICATIONS: Proactive management in addressing weight, mood, and sleep problems should be included in the multidisciplinary care of adolescents with SLE to improve their health and well-being.
Assuntos
Lúpus Eritematoso Sistêmico , Qualidade de Vida , Adolescente , Humanos , Criança , Inquéritos e Questionários , Tailândia/epidemiologia , Estudos Transversais , Sono , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/psicologiaRESUMO
Patients with childhood-onset systemic lupus erythematosus (cSLE) are at risk of becoming short adults. To evaluate the growth patterns and risk factors of short final height, a retrospective study was conducted in 97 patients (87 females, 90%) with cSLE who grew from the time of diagnosis and reached their final height. The primary outcome was the final height. Participants were divided into participants with short final height (final height standard deviation score (HSDS) < - 2, n = 22, 23%) and participants with normal final height (final HSDS ≥ - 2, n = 75, 77%). At diagnosis, the mean age was 11.3 ± 2.4 years and HSDS was - 0.5 ± 1.3. The participants reached the final height of 1.51 ± 0.08 m (final HSDS - 1.3 ± 0.1) at mean age of 16.2 ± 2.3 years. The HSDS of participants with short final height steadily declined throughout the course of SLE (p = 0.02), and were significantly lower than participants with normal final height at any time point (p < 0.001). In participants with normal final height, HSDS significantly declined from baseline until 2 years after diagnosis (p = 0.01), and then became stable thereafter. The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.Conclusion: A substantial number of the participants with cSLE became short adults. Adequate nutrition and corticosteroid minimization should be emphasized in patients at high risk for short final height. What is known? ⢠Growth failure is common in SLE due to many risk factors including chronic inflammation, malnutrition, and long-term use of corticosteroids. ⢠In comparison to growth failure, final height is a better indicator of growth as the prevalence of growth failure is variable depending on definitions, patient age and pubertal status. What is new? ⢠Nearly one fourth of children with SLE have short final height. ⢠The independent risk factors for short final height were the male sex, short stature at diagnosis, low body weight at final height, and cumulative corticosteroid dose.
Assuntos
Lúpus Eritematoso Sistêmico , Adolescente , Adulto , Idade de Início , Estatura , Criança , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The administration of induction immunosuppressive therapy to children with newly diagnosed systemic lupus erythematosus (SLE) and concurrent infections can lead to unfavourable outcomes. This study was conducted to describe characteristics of infections occurring before the initiation of immunosuppressants in hospitalized children with newly diagnosed SLE in underresourced areas. METHODS: Medical records of paediatric patients with the diagnosis of SLE, who were admitted to a university-based hospital from 2002 to 2018, were reviewed. Only patients younger than 18 years of age with newly diagnosed SLE were included in the study. The primary outcome was infection before the administration of immunosuppressants. Logistic regression analysis was used to determine factors associated with infection and adjusted odds ratio (OR). The diagnostic accuracy of CRP was assessed. RESULTS: Infections were confirmed in 52/124 (41.9%) children. Pathogens were identified in 24 (46.2%) patients with bacterial predominance. The most common site was respiratory infections (36.5%). Fever and serosal involvement were more prevalent in patients with infection. Serum CRP levels were significantly higher in patients with infection than in those without infection (median 5.5 mg/L (interquartile range (IQR) 3.6-76.3 mg/L) vs. 3.5 mg/L (IQR 3.0-3.6 mg/L), p = 0.004). When a positive CRP level of >5 mg/L was used, positive CRP was found with a higher prevalence in patients with infection and was independently associated with infection (adjusted odds ratio (OR) = 28.6, 95% confidence interval (CI) 2.3-350.6; p = 0.009). Patients with infection had a longer hospital stay than patients without infection (median 20 days (IQR 13-25 days) vs. 15 days (IQR 9-24 days), p = 0.04). Sensitivity, specificity, positive predictive value and negative predictive value with 95% CI of CRP >5 mg/L were 62.5% (35.4-84.8%), 88.9% (65.3-98.6%), 80.3% (51.0-94.1%) and 76.6% (63.1-86.3%), respectively. CONCLUSIONS: Infections were common among hospitalized children with newly diagnosed SLE. Children with infections had a prolonged course of hospitalization. Positive CRP was associated with a predisposition towards infection. However, the diagnostic accuracy of CRP requires further validation in a larger study.
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Proteína C-Reativa/análise , Febre/diagnóstico , Infecções/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Adolescente , Criança , Feminino , Febre/sangue , Hospitais Universitários , Humanos , Infecções/sangue , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/sangue , Masculino , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , TailândiaRESUMO
BACKGROUND: Information on long-term renal outcome of pediatric glomerulonephritis associated with crescent formation is limited. A single center retrospective study was conducted to assess long-term renal survival and to determine whether the 2010 classification for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis can predict renal outcome in pediatric glomerulonephritis associated with crescent formation. METHODS: Biopsy and clinical data of children, aged ≤ 18 years with ≥ 10 glomeruli and ≥ 10% crescentic glomeruli during January 1998 to December 2015, were reviewed. Biopsies were classified according to the 2010 classification into focal, crescentic, mixed, and sclerotic classes. The clinical endpoint was end-stage renal disease (ESRD). RESULTS: Of 72 children, 14 patients (19.4%) had positive ANCA. The biopsy indication was rapidly progressive glomerulonephritis in 38 patients (52.8%) and 22 patients (30.6%) required dialysis at onset. Lupus nephritis was the most common diagnosis (43.1%), followed by IgA nephropathy/Henoch-Schoenlein purpura (HSP) (22.2%). ESRD occurred in 18 patients (25%) and the risk of ESRD differed among the histological classifications (p < 0.001). Dialysis at onset and sclerotic class was independent predictors of ESRD in an adjusted model. The risk of ESRD was four-fold higher in patients requiring dialysis at onset and 7.7-fold higher in sclerotic patients than in crescentic patients. CONCLUSIONS: The probability of ESRD was substantial in pediatric glomerulonephritis associated with crescent formation. The 2010 classification is useful for establishing long-term renal prognosis. Future research is required to validate whether histological classification could be a determinant in therapeutic guideline modification, since long-term renal prognosis is different in each class.
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Glomerulonefrite/patologia , Rim/patologia , Adolescente , Criança , Feminino , Glomerulonefrite/classificação , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Estudos Retrospectivos , Tailândia/epidemiologiaRESUMO
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.
Assuntos
Povo Asiático/genética , Cromossomos Humanos X/genética , Genes Ligados ao Cromossomo X , Lúpus Eritematoso Sistêmico/genética , Ribose-Fosfato Pirofosfoquinase/genética , China , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background: Up to >80% of sexually active adults will become infected with human papillomavirus (HPV) during their lifetime. Persistent HPV infection can result in cervical, vulvovaginal, penile and anogenital cancer. Clinical studies have shown the efficacy of three doses of quadrivalent HPV-6/11/16/18 L1 virus-like particle (VLP) vaccination, at Day 0, Month 2 and Month 6, to lower the occurrence of HPV infection and its complications. However, immunogenicity and safety of the HPV vaccine have not been proven in the chronic kidney disease (CKD) population. Methods: Sixty CKD stage IV, V and VD patients were enrolled for quadrivalent HPV-6/11/16/18 vaccination. A dose of vaccine was given at Day 0, Month 2 and Month 6. Each dose contained 20 µg HPV-6 L1 VLP, 40 µg HPV-11 L1 VLP, 40 µg HPV-16 L1 VLP and 20 µg HPV-18 L1 VLP, along with 225 µg of amorphous aluminum hydroxyphosphate sulfate adjuvant. HPV type-specific antibody response to neutralizing epitopes on HPV-6/11/16/18 was performed by multiplexed, competitive Luminex® immunoassays (cLIA) at Day 0 and Month 7. Results: At Day 0, anti-HPV seropositivity was 0-6.6% depending on HPV genotype. Patients who received three doses of vaccine had 98.2, 100, 100 and 98.2% seropositivity for genotypes 6/11/16/18, respectively. The average cLIA at Month 7 for genotypes 6/11/16/18 were 928.4 ± 231.1, 1136.1 ± 264.6, 6951.0 ± 1872.3 and 2196.3 ± 761.2 milliMerck units (mMu)/mL, respectively. No serious vaccine-related adverse events were observed. Conclusions: Quadrivalent HPV vaccine has been well tolerated, is safe and provides excellent immunogenicity in late-stage CKD.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Insuficiência Renal Crônica/prevenção & controle , Adolescente , Adulto , Anticorpos Antivirais/sangue , Criança , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Humanos , Imunoensaio , Masculino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Prevalência , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/virologia , Tailândia/epidemiologia , Vacinação , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P(_combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P(_combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P(_combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.
Assuntos
Cromossomos Humanos Par 11 , RNA Helicases DEAD-box/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lúpus Eritematoso Sistêmico/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Receptores CXCR5/genética , Povo Asiático/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
OBJECTIVES: Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility. METHODS: The study involved a total of 1â 659 cases and 3â 398 controls in the discovery stage and 2â 612 cases and 3â 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction. RESULTS: Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate<0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets. CONCLUSIONS: Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.
Assuntos
Proteínas Ativadoras de 5-Lipoxigenase/genética , Povo Asiático/genética , Antígeno B7-1/genética , Epistasia Genética/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Polimorfismo de Nucleotídeo Único , Tetraspaninas , Receptor fas/genéticaRESUMO
PURPOSE: We evaluated risk factors and assessed predicted probabilities for grade III or higher vesicoureteral reflux (dilating reflux) in children with a first simple febrile urinary tract infection and normal renal and bladder ultrasound. MATERIALS AND METHODS: Data for 167 children 2 to 72 months old with a first febrile urinary tract infection and normal ultrasound were compared between those who had dilating vesicoureteral reflux (12 patients, 7.2%) and those who did not. Exclusion criteria consisted of history of prenatal hydronephrosis or familial reflux and complicated urinary tract infection. The logistic regression model was used to identify independent variables associated with dilating reflux. Predicted probabilities for dilating reflux were assessed. RESULTS: Patient age and prevalence of nonEscherichia coli bacteria were greater in children who had dilating reflux compared to those who did not (p = 0.02 and p = 0.004, respectively). Gender distribution was similar between the 2 groups (p = 0.08). In multivariate analysis older age and nonE. coli bacteria independently predicted dilating reflux, with odds ratios of 1.04 (95% CI 1.01-1.07, p = 0.02) and 3.76 (95% CI 1.05-13.39, p = 0.04), respectively. The impact of nonE. coli bacteria on predicted probabilities of dilating reflux increased with patient age. CONCLUSIONS: We support the concept of selective voiding cystourethrogram in children with a first simple febrile urinary tract infection and normal ultrasound. Voiding cystourethrogram should be considered in children with late onset urinary tract infection due to nonE. coli bacteria since they are at risk for dilating reflux even if the ultrasound is normal.
Assuntos
Infecções Urinárias/complicações , Refluxo Vesicoureteral/complicações , Refluxo Vesicoureteral/patologia , Criança , Pré-Escolar , Dilatação Patológica , Feminino , Febre/complicações , Humanos , Lactente , Rim/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ultrassonografia , Bexiga Urinária/diagnóstico por imagemRESUMO
PURPOSE: To determine the diagnostic accuracy of anteroposterior renal pelvic diameter (APD) measurement and the society for fetal urology (SFU) grading in neonatal ultrasonography (USG) for detecting uropathy in newborns having antenatal isolated hydronephrosis (IH), characterized by hydronephrosis without ureter and bladder abnormalities, and to study time to resolution and factors predicting resolution of insignificant hydronephrosis. METHODS: Ninety-six healthy newborns (129 kidneys) with IH, who underwent USG at age 7-30 days and voiding cystourethrography (VCUG) in conjunction with diuretic renography (DR) if APD > 10 mm or SFU grade 3-4 in neonatal USG, and at least a 12-month follow-up were divided into significant and insignificant hydronephrosis using the combined data of sequential USG, VCUG, and DR as the reference standard. RESULTS: Areas under the receiver operating characteristic plots (95 % CI) were 0.86 (0.79-0.94) versus 0.81 (0.73-0.89); p = 0.08, and 87.6 versus 79.8 % of cases were correctly classified, for APD ≥ 16 mm versus SFU grade 4, respectively. Ureteropelvic junction obstruction (UPJO) was the most common uropathy diagnosed. Of 85 kidneys with insignificant hydronephrosis, 57 underwent spontaneous resolution. The resolution rates were 24, 40, and 68 % at age 6, 12, and 24 months, respectively. APD was the only independent factor predicting resolution with the hazard ratio of 0.83 (95 % CI 0.74-0.92; p = 0.001). CONCLUSIONS: In IH, neonatal USG was a useful diagnostic tool to detect uropathy, mainly UPJO. Further investigation should be recommended when APD ≥ 16 mm or SFU grade 4.
Assuntos
Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Recém-Nascido , Pelve Renal/diagnóstico por imagem , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Ultrassonografia , Ureter/anormalidades , Bexiga Urinária/anormalidadesRESUMO
BACKGROUND: Data on global (IV-G) and segmental (IV-S) diffuse proliferative lupus nephritis (DPLN) in children are lacking. METHODS: To determine the clinicopathology and prognosis of DPLN subclasses IV-G and IV-S, we analyzed the clinical, laboratory, and demographic data of 56 children aged <18 years diagnosed with DPLN [36 (64.3%) with IV-G; 20 (35.7%) with IV-S] between 2004 and 2013. Clinical endpoints were: (1) complete remission (CR), (2) chronic kidney disease [CKD; defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) or end-stage renal disease (ESRD)], and (3) death. RESULTS: Proteinuria and the activity index were higher in patients with IV-G (p < 0.05). Global endocapillary proliferation and leukocyte exudation were predominant in IV-G patients, whereas segmental endocapillary proliferation was predominant in patients with IV-S (p < 0.005). CR rates in IV-G and IV-S patients were 50 and 60%, respectively (p = 0.47). Renal survival rates, defined as an eGFR of ≥60 mL/min/1.73 m(2), were 93, 78, and 64% at 1, 5, and 10 years, respectively. Patient survival rates at 1, 5, and 10 years were 98, 96, and 91%, respectively. Patient and renal survival rates were similar in both subclasses. CONCLUSIONS: Although patients with IV-G and IV-S displayed some clinical and histopathological disparities, renal outcomes were similar. The majority of children with DPLN reached adulthood but accrued significant renal damage. Treatment regimens which can slow the progression of CKD are needed.
Assuntos
Nefrite Lúpica/complicações , Nefrite Lúpica/patologia , Adolescente , Criança , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Nefrite Lúpica/mortalidade , Masculino , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Estudos RetrospectivosRESUMO
UNLABELLED: Timely antibiotic initiation for acute pyelonephritis (APN) can prevent renal complications. We investigated whether urine heparin binding protein (UHBP), a cytokine released from activated neutrophils, was a useful diagnostic tool for APN. Febrile children with presumed APN were prospectively enrolled between January and September 2013, and divided into two groups based on urine cultures. UHBP levels were measured at enrollment in all children and 1 month after antibiotic treatment in children with APN. UHBP levels in children with APN at baseline and 1 month versus controls were 47.0 ± 8.4 and 16.6 ± 3.8 vs. 15.0 ± 2.9 ng/mL, respectively (p < 0.001). Test performance characteristics were calculated against a gold standard of positive urine cultures and compared with leukocyte esterase (LE) and nitrite measured by dipsticks and pyuria by microscopy. The sensitivity and specificity for UHBP levels ≥34 ng/mL were 100 and 100 %. Spearman's rank coefficient was used to assess the associations between routine laboratory tests and UHBP levels. Significant positive correlations were found with pyuria grade (Spearman's rho = 0.62; p < 0.001), neutrophil count (rho = 0.38; p = 0.03), and platelet count (rho = 0.39; p = 0.03). CONCLUSIONS: UHBP is a valid adjunctive diagnostic tool for aiding clinicians in making rapid treatment decisions for APN.