RESUMO
BACKGROUND: Congenital anomalies of kidney and urinary tract (CAKUT) are the leading causes of chronic kidney disease (CKD) in childhood. Determining the clinical course, outcome, and prognostic factors of this heterogeneous disease group is important to provide appropriate management and follow-up. Therefore, we aimed to identify the risk factors of CKD in CAKUT and the differences in clinical courses between disease subgroups. METHODS: Three hundred patients (M/F: 203/97) divided into 16 CAKUT categories were enrolled in the study. Logistic regression and survival analyses were performed to determine the risk factors for CKD that is defined as estimated GFR (eGFR) lower than 90 ml/min/1.73 m2 for at least 6 months. RESULTS: The median age of the study population at the time of the diagnosis was 0.6 years (IQR; 0.1-4.0 years). Among available prenatal diagnoses (n= 138), hydronephrosis (HN) (n= 83; 60.1%) and multicystic dysplastic kidney (MCDK) (n= 39; 28.2%) were the most frequently encountered ones. A total of 24 patients had CKD, and 13 of them (54.1%) progressed to end stage renal disease (ESRD). Patients with posterior urethral valve (PUV) had CKD and ESRD more frequently when compared to the other diagnostic groups (p < 0.001 for CKD, and p < 0.001 for ESRD). Furthermore, the PUV subgroup progressed to ESRD (median 3.63 years) earlier than the other subgroups. The diagnosis of PUV, proteinuria on the first admission, vesicoureteral reflux, and oligohydramnios were identified as independent predictors for CKD in the multivariate logistic regression analysis. CONCLUSIONS: Knowing predictive factors for CKD in patients with CAKUT is valuable for physicians in order to determine appropriate treatment strategies and prognosis.
Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Refluxo Vesicoureteral , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Rim , Gravidez , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de RiscoRESUMO
Düzova A, Gülhan B, Topaloglu R, Özaltin F, Cengiz AB, Yetimakman AF, Dogru D, Güçer S, Besbas N. BK virus associated nephropathy and severe pneumonia in a kidney transplanted adolescent with Schimke immune-osseous-dysplasia. Turk J Pediatr 2019; 61: 111-116. Patients with juvenile onset Schimke immune-osseous-dysplasia (SIOD) have less severe symptoms and can survive in the second and third decade of life. We present an 18 year-old adolescent with juvenile onset SIOD who was diagnosed after renal transplantation and developed BK virus associated nephropathy (BKVAN) and severe pneumonia during follow-up. The patient developed nephrotic syndrome, unresponsive to immunosuppressives, at the age of 8 years. He had a history of meningitis, short stature, microcephaly, prominent ears, and bilateral cryptorchidism. A renal transplantation was performed at the age of 15 years. During follow-up, he suffered from leucopenia, urinary tract infections, herpes labialis, and candida esophagitis. Sanger sequencing of SMARCAL1 revealed a missense mutation on exon 11 (R586W). A renal biopsy performed after a sharp increase in serum creatinine (without significant viremia) revealed BKVAN which responded to sirolimus monotherapy and cidofovir. Three months later, he suffered from productive cough and dyspnea with diffuse ground glass pulmonary infiltrates. His clinical situation deteriorated and non-invasive mechanical ventilation was started. Cidofovir (2 mg/kg) was re-started weekly for a possible BKV pneumonia with intravenous immunoglobulin. After 5 doses of cidofovir and intense antibiotic regime, his dyspnea resolved with stable graft functions. In our case; BKVAN, which developed without significant viremia, and possibly associated pneumonia were treated successfully with cidofovir and sirolimus monotherapy.
Assuntos
Síndrome Nefrótica/virologia , Pneumonia Viral/complicações , Infecções por Polyomavirus/complicações , Transplantados , Adolescente , Arteriosclerose/complicações , Vírus BK , DNA Helicases/genética , Humanos , Transplante de Rim , Masculino , Mutação de Sentido Incorreto , Síndrome Nefrótica/complicações , Osteocondrodisplasias/complicações , Doenças da Imunodeficiência Primária/complicações , Embolia Pulmonar/complicaçõesRESUMO
AIM: Familial Mediterranean fever (FMF) results from MEFV gene mutations. E148Q is a variant of unknown significance in MEFV. We aimed to define characteristics of FMF patients homozygous for E148Q, check for other MEFV variants in a subgroup, and compare the characteristics with FMF patients carrying other mutations. METHODS: Thirty FMF patients homozygous for E148Q were reviewed. MEFV variant analysis was performed with strip assay. All MEFV exons were screened by direct DNA sequencing in 14 randomly selected E148Q/E148Q patients. E148Q was also checked in 100 healthy adolescents. We compared the characteristics of FMF patients between three groups: E148Q/E148Q (n = 30), M694V/E148Q (n = 19) and exon 10/exon 10 MEFV mutations (n = 48). RESULTS: Among 30 FMF patients (E148Q/E148Q), the median age at disease onset and diagnosis were 60 (12-168) and 94 (41-196) months, respectively. Fifteen (50%) patients had mild, 14 (46.7%) moderate and one (3.3%) had severe disease. Twenty-two (73.3%) patients had complete, seven (23.3%) had incomplete response to colchicine, while only one was unresponsive. The detected MEFV variants in 14 E148Q/E148Q FMF patients were as follows: R314R (n = 9; 64.3%), E474E (n = 13; 92.9%), Q476Q (n = 13; 92.9%), D510D (n = 13; 92.9%), and P588P (n = 8; 57.1%). The E148Q allele frequency was 6.5% in healthy adolescents. When compared to FMF patients with other MEFV mutations, disease onset was later, disease was less severe and the ratio of patients responding completely to colchicine was higher in E148Q/E148Q patients. CONCLUSION: Patients homozygous for E148Q and negative for other pathogenic MEFV variants may display FMF phenotype and may experience moderate/severe disease activity, although the disease may be milder when compared to FMF patients with other mutations.
Assuntos
Febre Familiar do Mediterrâneo/genética , Homozigoto , Mutação , Pirina/genética , Adolescente , Criança , Pré-Escolar , Colchicina/uso terapêutico , Análise Mutacional de DNA , Éxons , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Humanos , Masculino , Fenótipo , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration. METHODS: A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation. RESULTS: Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m2, proteinuria was 1,008 (IQR 281-1,567) mg/m2/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m2, P=0.61). CONCLUSIONS: ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective.
Assuntos
Albuminúria/diagnóstico , Falência Renal Crônica/diagnóstico , Síndrome Nefrótica/diagnóstico , Proteínas Quinases/genética , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Adolescente , Adulto , Albuminúria/tratamento farmacológico , Albuminúria/genética , Albuminúria/urina , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Diferencial , Resistência a Medicamentos , Feminino , Seguimentos , Testes Genéticos , Taxa de Filtração Glomerular , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/genética , Masculino , Mutação , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/genética , Fatores de Tempo , Resultado do Tratamento , Turquia , Ubiquinona/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant morbidity and mortality. Its genetic heterogeneity impacts its clinical presentation, progress, and outcome, and there is no consensus on its clinical management. METHODS: To identify the characteristics of aHUS in Turkish children, an industry-independent registry was established for data collection that includes both retrospective and prospective patients. RESULTS: In total, 146 patients (62 boys, 84 girls) were enrolled; 53 patients (36.3%) were less than 2 years old at initial presentation. Among the 42 patients (37.1%) whose mutation screening was complete for CFH, CFI, MCP, CFB, C3, DGKE, and CHFR5 genes, underlying genetic abnormalities were uncovered in 34 patients (80.9%). Sixty-one patients (41.7%) had extrarenal involvement. During the acute stage, 33 patients (22.6%) received plasma therapy alone, among them 17 patients (51.5%) required dialysis, and 4 patients (12.1%) were still on dialysis at the time of discharge. In total, 103 patients (70.5%) received eculizumab therapy, 16 of whom (15.5%) received eculizumab as a first-line therapy. Plasma therapy was administered to 84.5% of the patients prior to eculizumab. In this group, renal replacement therapy was administered to 80 patients (77.7%) during the acute period. A total of 3 patients died during the acute stage. A total of 101 patients (77.7%) had a glomerular filtration rate >90 mL/min/1.73 m2 at the 2-year follow-up. CONCLUSIONS: The Turkish aHUS registry will increase our knowledge of patients with aHUS who have different genetic backgrounds and will enable evaluation of the different treatment options and outcomes.
Assuntos
Síndrome Hemolítico-Urêmica Atípica/mortalidade , Síndrome Hemolítico-Urêmica Atípica/terapia , Transfusão de Sangue/mortalidade , Imunossupressores/uso terapêutico , Sistema de Registros , Diálise Renal/mortalidade , Adolescente , Síndrome Hemolítico-Urêmica Atípica/genética , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Comorbidade , Feminino , Predisposição Genética para Doença/genética , Humanos , Lactente , Masculino , Projetos Piloto , Prevalência , Diálise Renal/estatística & dados numéricos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
OBJECTIVES: The aim of this study was to present the genetic and clinical data of the largest cohort of Turkish cryopyrin-associated periodic syndromes (CAPS) patients. METHODS: This is a two-centre descriptive study of Turkish children with clinical diagnosis of CAPS. NLRP3 analyses were performed by Sanger sequencing and by massively parallel sequencing. ASC dependent NF-κB activation and transfection-induced THP-1 cell death assays determined the functional consequences of the detected variants. Disease activity and response to anti interleukin 1 (anti-IL-1) treatment was also assessed. RESULTS: Heterozygous germline NLRP3 mutation was detected in 8 of 14 enrolled patients (57.1%). Two novel somatic mutations Y560H and G307D were found which induced both THP-1 cell death and ASC dependent NF-kB activation. With anti-IL-1 treatment the disease activity was improved in all patients except one. Except two patients with macrophage activation syndrome (MAS) attack, there were no serious adverse events requiring hospitalisation. CONCLUSIONS: CAPS should be considered in all patients with typical symptoms even if Sanger-based genetic analysis is negative, since a considerable number of patients have mosaicism. Treatment should be patient-tailored and MAS should be considered as a rare complication.
Assuntos
Síndromes Periódicas Associadas à Criopirina/genética , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Adolescente , Fatores Etários , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Proteínas Adaptadoras de Sinalização CARD , Linhagem Celular , Criança , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Análise Mutacional de DNA , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Heterozigoto , Humanos , Imunossupressores/uso terapêutico , Síndrome de Ativação Macrofágica/genética , Masculino , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fenótipo , Fatores de Risco , Transfecção , Resultado do Tratamento , TurquiaRESUMO
Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.
Assuntos
Síndrome Hemolítico-Urêmica Atípica/terapia , Nefrologia/normas , Adolescente , Fatores Etários , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/imunologia , Criança , Pré-Escolar , Terapia Combinada , Ativação do Complemento/efeitos dos fármacos , Consenso , Comportamento Cooperativo , Monitoramento de Medicamentos , Humanos , Fatores Imunológicos/uso terapêutico , Lactente , Recém-Nascido , Cooperação Internacional , Transplante de Rim , Transplante de Fígado , Monitorização Imunológica , Seleção de Pacientes , Troca Plasmática , Valor Preditivo dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Amyloidosis may complicate autoinflammatory diseases (AID). We aimed to evaluate the renal biopsy findings, and clinical and laboratory parameters in patients with AID-associated amyloidosis who have responded to anti-interleukin 1(IL1) treatment. METHODS: Two children with systemic juvenile idiopathic arthritis and one with cryopyrin-associated periodic syndrome diagnosed as having reactive amyloidosis were treated with anti-IL1 drugs. The renal histopathological findings at the time of diagnosis of amyloidosis and after the onset of anti-IL1 were evaluated according to the amyloid scoring/grading system. RESULTS: The median age of disease onset and diagnosis of amyloidosis were 3 and 12 years, respectively. Anakinra was started in all; however, anakinra caused a local cutaneous reaction in one, thus canakinumab was commenced. Proteinuria improved in all. Control renal biopsies were performed a median of 3 years after the first biopsies. The renal amyloid prognostic score did not improve in patient 1, and progressed in patients 2 and 3. The renal amyloid grade progressed in patient 2. CONCLUSIONS: This is the first series demonstrating progression of renal tissue damage after the improvement of proteinuria with anti-IL 1 in AID-associated amyloidosis. Anti-IL1 drugs are important to prevent further amyloid accumulation; however, new treatment strategies are needed to target the amyloid deposits.
Assuntos
Amiloidose/tratamento farmacológico , Artrite Juvenil/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Adolescente , Amiloidose/diagnóstico , Amiloidose/imunologia , Artrite Juvenil/diagnóstico , Artrite Juvenil/imunologia , Biópsia , Criança , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/imunologia , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Rim/imunologia , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/imunologia , Masculino , Proteinúria/tratamento farmacológico , Proteinúria/imunologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Our purpose was to assess the relationship between serum fibroblast growth factor 23 (FGF23) and left ventricular function, carotid intima-media thickness (CIMT) and laboratory features in children on peritoneal dialysis (PD). The study population consisted of 17 patients (11 female; median age 7.83 years, range 0.66-17.75) undergoing PD for 22 months (range 2-98). Serum FGF23, serum phosphorus, calcium, intact parathyroid hormone (iPTH), 25(OH) vitamin D, 1,25(OH)2 vitamin D and Kt/V urea, left ventricular mass (LVM) and LVM index (LVMI) were assessed. Median FGF23 level was 29.92 pg/ml (22.7-74.76), phosphorus was 5.2 mg/dl (3.1-9.9), iPTH was 438 pg/ml (16-1446), 25(OH) vitamin D was 11 ng/ml (5-35), 1,25(OH)2 vitamin D was 11 pg/ml (2-106), Kt/V urea was 2.33 (1.01-3.84). FGF23 level was independently associated with Kt/V urea (p<0.001). We found that effective dialysis may be the leading determinant of FGF level, independent from the calcium-phosphorus-PTH axis, in pediatric PD patients.
Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Diálise Peritoneal/métodos , Adolescente , Cálcio/sangue , Espessura Intima-Media Carotídea , Criança , Pré-Escolar , Estudos Transversais , Ecocardiografia , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Lactente , Masculino , Hormônio Paratireóideo/sangue , Diálise Peritoneal/efeitos adversos , Fósforo/sangue , Função Ventricular Esquerda/fisiologia , Vitamina D/sangueRESUMO
Monocyte chemoattractant protein-1 (MCP-1) is a highly specific chemokine for monocytes and plays roles in pathogenesis of various renal diseases. The aim of this study is to investigate the effect of MCP1 2518 A/G polymorphism on the incidence and clinical course of focal segmental glomerulosclerosis (FSGS) in children. MCP1 2518 A/G genotype was identified by PCR-RFLP in 60 biopsy-proven FSGS patients, 76 steroid sensitive nephrotic syndrome (SSNS) patients, and 96 healthy children. MCP-1 levels in urine and serum were measured by ELISA in all patients and the correlations of genotype with MCP-1 levels and clinical outcome were evaluated. The genotype frequencies for MCP1 were similar in all groups. The percentage of patients who develop chronic renal failure was higher in patients with AA allele compared to GA or GG alleles (46% vs. 35% respectively, p < 0.01, Odds ratio: 1.59). Serum MCP-1 levels were similar in all groups, whereas urinary MCP-1 levels of the patients with FSGS (1680 pg/mg creatinine) were significantly higher than that of patients with SSNS (365 pg/mg creatinine, p < 0.05) and healthy controls (348 pg/mg creatinine; p < 0.05). Urinary MCP-1 levels were correlated with the degree of proteinuria in FSGS group (r = 0.529, p = 0.016). Our results suggest that the AA genotype might be a risk factor for the progression of renal disease in FSGS and MCP1 genotyping may help the physicians to predict prognosis in these patients.
Assuntos
Quimiocina CCL2/genética , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Falência Renal Crônica/genética , Síndrome Nefrótica/genética , Adolescente , Alelos , Biópsia , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Quimiocina CCL2/urina , Criança , Pré-Escolar , Progressão da Doença , Feminino , Genótipo , Humanos , Lactente , Masculino , Polimorfismo Genético , Prognóstico , Proteinúria/urinaRESUMO
Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. Approximately 5-10 % of patients are unresponsive to colchicine. Aim of this study was to determine the short- and long-term efficacy and safety of anti-interleukin 1 (anti-IL1) and anti-tumor necrosis factor agents in colchicine-resistant FMF cases in Turkish children and adolescents. This is a single-center retrospective case series of colchicine-resistant FMF patients. The included patients were treated with biologics for either colchicine resistance or because of one of the following: (1) amyloidosis, (2) recurrent prolonged febrile myalgia and frequent need of steroid and (3) persistent arthritis. Colchicine resistance was defined as at least one attack per month for three consecutive months and elevated erythrocyte sedimentation rate or C-reactive protein or serum amyloid A in-between attacks despite taking adequate dose of colchicine. Response to biologicals was evaluated by the Autoinflammatory Diseases Activity Index (AIDAI) score sheet, patients/parents'/physicians' global assessment of disease severity and laboratory parameters every 3-6 months. Fourteen patients were included in the study. Three patients were treated with etanercept for median 7 months (range 3-11 months), and all patients had to be switched to anti-IL1 treatment because of adverse effects and/or partial response. Eleven patients were treated with anakinra with a median duration of 8 months (4-60 months). Nine patients responded to treatment at the third month, but four of them switched to canakinumab because of noncompliance, local side effects and active arthritis. Nine patients were treated with canakinumab, all responded. At follow-up, in two patients the dose had to be increased, and on the other hand, in three patients the interval was increased to every 12-16 weeks. In three patients, anti-IL1 treatment could be stopped and they are fine with colchicine. This case series describes the largest cohort of colchicine-resistant FMF patients in childhood and adolescence. Anti-IL1 treatment is a safe and effective therapy to control inflammation. The treatment should be modified and decided for each patient on an individual basis.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Colchicina/uso terapêutico , Etanercepte/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Adolescente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Criança , Pré-Escolar , Etanercepte/efeitos adversos , Febre Familiar do Mediterrâneo/diagnóstico , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) are caused primarily by mutations in genes that encode structural and regulatory proteins of the glomerular filtration barrier. The aim of this study was to determine genotype-phenotype correlations and prognosis in patients with CNS and INS. METHODS: NPHS1, NPHS2, LAMB2 and the eighth and ninth exons of WT1 were sequenced in 80 and 22 patients with CNS and INS, respectively. Genotype-phenotype correlations and survival were evaluated. RESULTS: Causative mutations were identified in 64.7 % of patients, of which NPHS1 mutations were the most common (37.4 %). The mutation detection rate was twofold higher in CNS patients than in INS patients (72.5 vs. 36.2 %). The most commonly mutated gene in CNS patients was NPHS1 (46.3 %) versus NPHS2 (13.6 %) and WT1 (13.6 %) in INS patients. NPHS2 mutations, female patients with NPHS1 mutations, and NPHS1 mutations affecting the transmembrane or intracellular domains of nephrin were associated with longer survival. CONCLUSIONS: Based on our present findings, the likelihood of identification of a genetic cause decreases with increasing age at diagnosis. The underlying genetic abnormality should be identified as early as possible, as this knowledge will facilitate clinicians in their prognostic prediction and enable patients to receive appropriate genetic counseling.
Assuntos
Estudos de Associação Genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Laminina/genética , Proteínas de Membrana/genética , Síndrome Nefrótica/genética , Idade de Início , Análise Mutacional de DNA , Feminino , Genes do Tumor de Wilms , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Síndrome Nefrótica/mortalidade , PrognósticoRESUMO
BACKGROUND: Immunoglobulin A vasculitis (IgA-V), formerly known as Henoch-Schönlein purpura (HSP), is the most common small vessel vasculitis in children. In recent years, the role of T cells in the pathogenesis of HSP/IgA-V has become a focus of research. METHODS: Renal biopsy specimens from 22 pediatric patients diagnosed with Henoch-Schönlein nephritis (patient group) were compared to normal renal tissue in nephrectomy specimens from 20 pediatric patients diagnosed with Wilms tumor (control group). All renal specimens were scored according to International Study of Kidney Disease in Children (ISKDC) and Oxford classification. Immunohistochemical analyses of interferon-gamma (IFN-γ), interleukin (IL)-4, IL-17 and FOXP3 expression were performed. RESULTS: All glomeruli and tubules of the HSP/IgA-V patients showed significantly higher IFN-γ and IL-17 expression than those of the control group. Glomerular IFN-γ and IL-17 staining grades correlated with the urinary protein/creatinine ratio (r = 0.62, p = 0.02 and r = 0.507, p = 0.016, respectively). IL-17 expression also correlated with the percentage of crescents (r = 0.518, p = 0.014). IL-4 staining was present in only nine of the 22 patient biopsies and did not correlate with any of the parameters studied. Interstitial areas of patient biopsies had more FOXP3+ cells/µm(2) than those of the control group (p < 0.001), but differences in glomerular and tubular FOXP3+ levels (cells/µm(2)) between the two groups were not statistically different. The ISKDC and Oxford scores did not correlate with any parameter studied. However, endocapillary hypercellularity did correlate with IFN-γ expression. CONCLUSIONS: Based on these results, we conclude that IFN-γ and IL-17 contribute to HSP/IgA-V in children.
Assuntos
Citocinas/imunologia , Vasculite por IgA/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , MasculinoRESUMO
This study was performed to evaluate the role of postnatal ultrasonography (US) in predicting the final diagnosis and need of surgery of antenatal hydronephrosis patients. One hundred and twenty six renal units (RUs) of 76 patients with diagnosis of antenatal hydronephrosis (ANH) were studied. An early postnatal US no later than the first week of life was requested. Voiding cystourethrography (VCUG) and/or diuretic renogram (MAG3) was performed in children who had persistent or worsening hydronephrosis to make a certain diagnose of etiology. US findings of different etiologies, and operated/nonoperated groups are compared. Regarding the renal pelvic anteroposterior diameter in the first week postnatal US; mild, moderate, severe, and no HN was detected in 48 (38.1%), 31 (24.6%), 24 (19.0%), and 23 (18.3%) RUs respectively. Eight RUs with a normal first postnatal US were found to have renal anomaly during follow up and 63% of these were vesicoureteral reflux (VUR). Kidneys with mild or moderate HN were likely to have transient dilatation while severe HN was likely to have obstruction. Postpartum follow-up of AHN is a dynamic process. Follow-up must be planned with optimum period of intervals according to clinic and US findings, to select the right patient for surgery or close follow-up.
Assuntos
Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Instituições de Assistência Ambulatorial , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Rim/patologia , Masculino , Cuidado Pós-Natal/métodos , GravidezRESUMO
Tacrolimus is a potent immunosuppressive agent widely used after organ transplantation. In this present study we present eight patients who complained of palpitation after kidney transplantation. Eight out of 31 patients who received tacrolimus after kidney transplantation suffered from tachycardia. Resting electrocardiography, 24 hours Holter monitorization, echocardiography were performed, and serum levels of cardiac troponin T, creatine kinase, CKMB, brain natriuretic peptide and tacrolimus were measured. The median time to palpitation after kidney transplantation was 30 days in seven patients, and one patient complained of palpitation five years after transplantation. Cardiovascular assessment revealed sinus tachycardia in all patients. Beta-blocker was instituted in five patients. After two months all patients were asymptomatic and their pulse rates were within normal limits. Transient sinus tachycardia is a frequent adverse event during tacrolimus therapy in children and young adults, at therapeutic levels. Patients may benefit from beta-blockers.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Taquicardia Sinusal/induzido quimicamente , Tacrolimo/efeitos adversos , Adulto , Criança , Creatina Quinase/sangue , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Peptídeo Natriurético Encefálico/sangue , Taquicardia Sinusal/diagnóstico , Taquicardia Sinusal/tratamento farmacológico , Tacrolimo/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to describe the incidence and contributory risk factors for thromboembolic complications in children with nephrotic syndrome (NS) and thrombosis. METHODS: Among 188 children with the diagnosis of NS (80 girls; mean age: 12.6 ± 5.4 years) followed up in our hospital for the last 5 years, 17 (9.0 %) children (16 boys) identified as having thromboembolic complications. All 17 children with NS and thrombosis were screened for laboratory risk factors for thrombosis. The diagnosis was confirmed by cranial magnetic resonance imaging, doppler ultrasonography, and echocardiography. RESULTS: Among 17 children with thrombosis, 14 (82.3 %) were found to have focal segmental glomerulosclerosis (FSGS) as underlying pathology by renal biopsy. The mean age of the thrombotic children was 4.5 ± 3.2 years at the diagnosis of NS and that was 7.1 ± 4.9 years at the time of thrombosis. The mean time from NS diagnosis to the first thrombosis development was 2.6 ± 2.3 years. Thrombosis occurred during the first year of NS in 9/17 (52.9 %) children. Most of the children (88.2 %) had venous thrombosis. Among the screened risk factors, high factor VIII level (64.7 %) was the leading factor followed by decreased antithrombin III level (29.4 %). Furthermore, 4 children had central venous catheters and 2 had infection as clinical risk factors for thrombosis. CONCLUSION: In this case series, subtype of FSGS, active disease state of NS, central venous catheters, and some inherited and acquired thrombotic risk factors have been identified as contributory factors for the development of thrombosis in children with NS.
Assuntos
Síndrome Nefrótica/complicações , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Adolescente , Idade de Início , Antitrombina III/metabolismo , Aspirina/uso terapêutico , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Cateteres Venosos Centrais/efeitos adversos , Criança , Pré-Escolar , Fator VIII/metabolismo , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Glomerulosclerose Segmentar e Focal/complicações , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Incidência , Lactente , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Síndrome Nefrótica/sangue , Síndrome Nefrótica/diagnóstico , Fatores de Risco , Trombectomia , Fatores de Tempo , Turquia/epidemiologia , Trombose Venosa/sangue , Trombose Venosa/terapiaRESUMO
BACKGROUND: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome. METHODS: Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010. Comprehensive, anonymous demographic and clinical data were collected. RESULTS: Seventy-one children were reported with an episode of aHUS during the audit period. Six cases occurred on a background of influenza A H1N1 infection. Of 71 patients, 59 (83 %) received plasma therapy within the first 33 days, of whom ten received plasma infusion only. Complications of central venous catheters occurred in 16 out of 51 patients with a catheter in-situ (31 %). Median time to enter hematological remission was 11.5 days, and eight of 71 (11 %) patients did not enter hematological remission by day 33. Twelve patients (17 %) remained dialysis dependent at day 33. CONCLUSIONS: This audit provides a snapshot of the early outcome of a group of children with aHUS in the months prior to more widespread use of eculizumab.
Assuntos
Síndrome Hemolítico-Urêmica Atípica/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Auditoria Clínica , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Guias de Prática Clínica como Assunto , Inquéritos e QuestionáriosRESUMO
BACKGROUND: We studied the cytokines secreted by the inflammatory T cell subgroups (IFN-γ and IL-17) and FOXP3 expression in lupus nephritis (LN) and analyzed associations with clinical and histopathological parameters. METHODS: Renal tissue samples of 39 LN patients were studied. Immunohistochemical staining was carried out with antibodies against IFN-γ, IL-17, and FOXP3. RESULTS: Both IFN-γ (+) and IL-17+ cells were statistically higher in LN tissues when compared with controls (p < 0.01). The cells in the tubulointerstitium were CD3 + CD4+ displaying a Th1 and Th17 phenotype, whereas the less intense population in the glomeruli was CD3-CD4-. Interstitial CD3 + CD4+ FOXP3+ cells were also significantly higher in LN biopsies than in control tissues (p < 0.01). IFN-γ (+) and IL-17+ cells were more intense among class IV LN as compared to class II, III LN (p < 0.01 and p = 0.001, respectively). Subsequently, when IL-17 and IFN-γ staining was compared between the proliferative LN classes, class III and IV patients had more intense staining compared to class II (all p < 0.05). IFN-γ immunostaining correlated positively with serum creatinine and negatively with albumin levels and glomerular filtration rate (GFR). IL-17 immunostaining correlated with proteinuria, requirement for pulse steroids, and SLEDAI renal score, and negatively with GFR. Furthermore, glomerular and interstitial IL-17 and IFN-γ stainings were significantly associated with various parameters of histological activity (p < 0.05). CONCLUSION: We suggest that IFN-gamma and IL-17 could have a role in the pathogenesis and progression of LN. The Th1 and Th17 cells may be imperative in the severity of LN. Recognizing the complexity of the immune pathways involved in lupus reminds us that targeting B cells only may not suffice to control the progression of the inflammation.
Assuntos
Fatores de Transcrição Forkhead/metabolismo , Interferon gama/metabolismo , Interleucina-17/metabolismo , Nefrite Lúpica/metabolismo , Adolescente , Idade de Início , Biópsia , Criança , Feminino , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/genética , Humanos , Imuno-Histoquímica , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-17/biossíntese , Interleucina-17/genética , Nefrite Lúpica/genética , Nefrite Lúpica/patologia , MasculinoRESUMO
OBJECTIVES: Enthesitis-related arthritis (ERA), is a complex genetic disease. Although HLA-B27 is well established, it does not explain all the genetic load in ERA. Familial Mediterranean fever (FMF), caused by mutations in the MEFV gene, is a frequent autoinflammatory disorder in the eastern Mediterranean. METHODS: We investigated the clinical and imaging features of 53 ERA patients, as well as the frequency of MEFV gene mutations in those who were HLA-B27 negative. RESULTS: The mean age of the patients was 13.3±2.2 years and 49 were boys. Peripheral arthritis was present in all and sacroiletis in 26 patients. Ultrasonography showed enthesitis in 6 patients of the tendons, whereas these were assessed to be normal by physical examination. Forty patients (75.5%) were positive for HLA-B27. MEFV analysis was performed for patients who were HLA-B27 negative. One patient refused MEFV analysis. 9 patients carried MEFV mutations: 2 patients were homozygous for M694V (both patients were subsequently started colchicine along with ERA treatment), 5 patients were heterozygous for M694V mutation, 1 patient was heterozygous for E148Q, and 1 patient was heterozygous for K695R mutation. None of the patients had features suggesting FMF at diagnosis of ERA; 1 patient subsequently developed typical FMF attacks. CONCLUSIONS: Our findings suggest that MEFV mutations may represent a susceptibility factor for ERA in the populations of the eastern Mediterranean.
Assuntos
Artrite Juvenil/genética , Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Predisposição Genética para Doença/genética , Adolescente , Criança , Feminino , Antígeno HLA-B27/genética , Heterozigoto , Homozigoto , Humanos , Masculino , Região do Mediterrâneo , Mutação Puntual , Pirina , TurquiaRESUMO
C3 glomerulopathy defines a subgroup of membranoproliferative glomerulonephritis (MPGN) characterized by complement 3 (C3)-positive, immunoglobulin-negative deposits in immunofluorescence microscopy. It comprises 3 clinical conditions: dense deposit disease, C3 glomerulonephritis, and complement factor H-related 5 (CFHR5) nephropathy. Mutations in genes encoding regulatory proteins of the alternative complement pathway have been described. A 16-year-old girl was admitted to the hospital due to periorbital edema. Nephrotic syndrome accompanied by low C3 level was diagnosed. Renal biopsy showed MPGN in light microscopy, only C3 deposits in immunofluorescence microscopy, and subendothelial electron dense deposits and capillary basement membrane thickening with double contour formation in electron microscopy. C3 nephritic factor and anti complement factor H antibody were negative. Complement factor H level was normal. Genetic screening showed a novel heterozygous p.Cys269Arg variation in the CFHR5 gene without any mutation in CFH and CFI genes. Eculizumab therapy was started but was unsuccessful at 10 months of follow-up. We have identified a novel heterozygous variation in CFHR5-related nephropathy presenting with nephrotic syndrome and persistently low C3 level, thus expanding the genetic and phenotypic spectrum of the disease. Eculizumab seems to be ineffective in this subtype.