Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Pediatr Nephrol ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993782

RESUMO

OBJECTIVES: Crescentic IgA nephropathy (C-IgAN) is defined as IgAN with more than 50% of glomeruli showing crescents. C-IgAN in children is rare; we investigate in detail for the first time. METHODS: We retrospectively analyzed the 515 consecutive children who were newly diagnosed with biopsy-proven IgAN between June 1976 and May 2010. We compared clinical and pathological findings between C-IgAN and non-C-IgAN. RESULTS: Among 515 cases of childhood IgAN, 25 children (4.9%) had C-IgAN. Of these 25, 16 children (64%) were referred to hospitals by annual school screening. Clinical findings showed significant differences in gross hematuria (76 vs. 50%, p = .03), excretion of proteinuria (1.9 vs. 0.5 g/day/m2, p < .0001), eGFR (102 vs. 108 ml/min/1.73 m2, p = .03), and duration from onset to renal biopsy (4.0 vs. 8.0 months, p = .04) between groups. Pathological findings showed significant differences in M1 (88 vs. 55%, p = .02), E1 (83 vs. 53%, p = .008), and presence of tubular atrophy/interstitial fibrosis (88 vs. 53%, p < .0001) between groups. The 16 children with C-IgAN were treated with prednisolone and immunosuppressant. Four cases (16%) reached chronic renal failure (eGFR < 60) at the latest observation (mean observation period: 6.0 ± 3.6 years). Patients with C-IgAN had significantly lower renal survival curve than non-C-IgAN patients according to Kaplan-Meier analysis (77.1% vs. 92.6% at 13 years, p < .0001). Compared with previous reports, however, they had better renal outcome. CONCLUSIONS: We confirmed the importance of school screening to find C-IgAN. Although most crescents (mean: 98.1%) of C-IgAN were cellular/fibrocellular, and acute lesions were well modified with combination therapy, the presence of tubular atrophy in C-IgAN may be the reason for poorer prognosis.

2.
Clin Exp Nephrol ; 24(1): 82-87, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541336

RESUMO

BACKGROUND: Although there is debate regarding the timing of initiation of renal replacement therapy (RRT) in adults with end-stage renal disease, there is a paucity of reliable epidemiological data on pediatric patients. The present study was performed to investigate current practice in Japan with regard to the timing of initiation of RRT in children based on estimated glomerular filtration rate (eGFR). METHODS: A total of 649 pediatric patients < 20 years old with eGFR at the initiation of RRT between 1 January 2006 and 31 December 2013 were included in the study. Baseline eGFR was calculated for each patient using the Schwartz formula. RESULTS: eGFR at the start of RRT was 12.1 mL/min/1.73 m2 [interquartile range (IQR) 8.4-16.3]. A total of 209 children (32.2%) had high eGFR (eGFR > 15 mL/min/1.73 m2) at the initiation of RRT. Initiation of RRT was more likely in those undergoing preemptive transplantation (PEKT) with high eGFR [odds ratio (OR) 4.16; 95% confidence interval (CI) 1.95-8.90, P < 0.001]. There were 31 deaths of various causes during follow-up, with infections representing the leading causes of death. CONCLUSIONS: The median eGFR at the initiation of RRT in children showed a wide range of variation. Further studies are needed to investigate the impact of the decision regarding when to initiate RRT in individual pediatric patients.

3.
Pediatr Nephrol ; 35(1): 17-24, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30564879

RESUMO

Patients with steroid-resistant nephrotic syndrome (SRNS) who develop resistance to immunosuppressive agents, defined as refractory SRNS, have poor renal outcomes. Although the chimeric anti-CD20 monoclonal antibody rituximab has shown efficacy for frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome, its efficacy for refractory SRNS remains uncertain due to limited data. According to previous case reports, 50.4% of patients with refractory SRNS showed clinical improvements after rituximab treatment. Remission rates in patients with initial steroid resistance and late steroid resistance were 43.9 and 57.7%, respectively, and 41.5 and 63.6% in patients with focal segmental glomerulosclerosis and minor glomerular abnormalities, respectively. However, various factors (race, disease severity, number of rituximab doses, concomitant treatments, and observation period) differed among these observational studies and their consensus may also have been affected by potential publication bias. Rituximab monotherapy may have some degree of efficacy and lead to satisfactory outcomes in a subset of patients with refractory SRNS. However, administration of concomitant treatments during rituximab-mediated B cell depletion, such as methylprednisolone pulse therapy, daily oral prednisolone therapy, and immunosuppressive agents, may lead to better outcomes in these patients. Large-scale, multi-center prospective studies are needed to evaluate the efficacy and safety of such regimens.

4.
J Matern Fetal Neonatal Med ; 33(1): 142-148, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29890876

RESUMO

Background: Neonatal hemochromatosis (NH) is a rare but serious disease causing fulminant hepatic failure. The recurrence rate of NH in a subsequent infant of a mother with an affected infant is 70-90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) treatment has been reported to be effective for preventing NH recurrence. However, data on the IgG concentrations during this treatment are limited.Objective: We report a Japanese experience and present a pharmacokinetic simulation model of IgG during IVIG treatment.Methods: Women with histories of pregnancy diagnosed with NH were treated with IVIG weekly from the second trimester until the end of gestation. Serum IgG levels during treatment were collected frequently and pharmacokinetics were simulated by a two-compartment model.Results: Six women were included during eight pregnancies. None experienced severe adverse events. Three out of eight infants showed temporary liver dysfunction, but none required any treatment. A simulation study showed that the estimated trough and peak levels of IgG concentrations during IVIG were 2000-3000 and 4000-5000 mg/dl, respectively.Conclusion: This treatment prevented the recurrence of NH in siblings in Japanese women. We examined the details of serum IgG concentrations and introduced a new pharmacokinetic simulation model of IgG concentrations during IVIG treatment.


Assuntos
Hemocromatose/prevenção & controle , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/farmacocinética , Cuidado Pré-Natal/métodos , Prevenção Secundária/métodos , Adulto , Quimioprevenção/métodos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunoglobulinas Intravenosas/efeitos adversos , Recém-Nascido , Infusões Intravenosas , Japão , Gravidez , Resultado da Gravidez , Recidiva , História Reprodutiva , Estudos Retrospectivos , Irmãos , Resultado do Tratamento
5.
BMC Nephrol ; 20(1): 293, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375087

RESUMO

BACKGROUND: Eighty percent of children with idiopathic nephrotic syndrome respond well to steroid therapy, but up to 50% of patients with steroid-sensitive nephrotic syndrome exhibit frequently relapsing (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Several studies identified the chimeric anti-CD20 monoclonal antibody rituximab as an effective treatment for patients with complicated FRNS/SDNS. Recent studies suggested that rituximab could also be a first-line treatment for early-stage uncomplicated FRNS/SDNS, although further studies are required to confirm its efficacy and safety. METHODS/DESIGN: We are conducting a multicenter, double-blind, randomized placebo controlled trial to investigate the efficacy and safety of rituximab for the treatment of childhood-onset early-stage uncomplicated FRNS/SDNS. Patients will be allocated to receive two 375 mg/m2 doses (maximum dose: 500 mg) of either rituximab or placebo. Investigators are permitted to request the disclosure of a subject's allocation code if he or she exhibits treatment failure. Additionally, if placebo-treated subjects display early relapse (a sign of treatment failure), they have the option to receive rituximab in an unblinded phase. The primary endpoint is relapse-free survival during the observation period. DISCUSSION: The results will provide important data on the use of rituximab for patients with uncomplicated FRNS/SDNS. In the future, rituximab treatment will enable most patients with uncomplicated FRNS/SDNS to discontinue or reduce steroid therapy without relapse, and it is possible that rituximab could represent an immunosuppressive therapy for these diseases. TRIAL REGISTRATION: This trial was prospectively registered to the JMACCT Clinical Trials Registry on September 6, 2018 (Trial ID: JMA-IIA00380 ).

6.
Pediatr Nephrol ; 34(8): 1457-1464, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30937553

RESUMO

BACKGROUND: The association between the clinical presentation of congenital anomalies of the kidney and urinary tract (CAKUT) and gene mutations has yet to be fully explored. METHODS: In this retrospective cohort study, we examined patients with CAKUT who underwent gene analysis. The analysis was performed in patients with bilateral renal lesions, extrarenal complications, or a family history of renal disease. The data from the diagnosis, gene mutations, and other complications were analyzed. RESULTS: In total, 66 patients with CAKUT were included. Of these, gene mutations were detected in 14 patients. Bilateral renal lesions were significantly related to the identification of gene mutations (p = 0.02), and no gene mutations were observed in patients with lower urinary tract obstruction (six patients). There was no significant difference in the rate of gene mutations between those with or without extrarenal complications (p = 0.76). The HNF1ß gene mutation was identified in most of the patients with hypodysplastic kidney with multicystic dysplastic kidney (six of seven patients). There was no significant difference in the presence or absence of gene mutations with respect to the renal survival rate (log-rank test p = 0.53). The renal prognosis varied, but the differences were not statistically significant for any of the gene mutations. CONCLUSIONS: CAKUT with bilateral renal lesions were significantly related to gene mutations. We recommend that CAKUT-related gene analysis be considered in cases of bilateral renal lesions. No gene mutations were observed in patients with lower urinary tract obstruction. The renal prognosis varied for each gene mutation.

7.
Allergol Int ; 68(3): 335-341, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30846304

RESUMO

BACKGROUND: Although the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial. METHODS: Hospitalized patients aged 1-17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 µg/kg/h) or salbutamol (500 µg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991. RESULTS: From December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were -2.9 (2.5) in the l-isoproterenol group and -0.9 (2.3) in the salbutamol group (difference -2.0, 95% confidence interval -3.1 to -0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group. CONCLUSIONS: Low-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.


Assuntos
Albuterol/uso terapêutico , Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/uso terapêutico , Isoproterenol/uso terapêutico , Administração por Inalação , Albuterol/administração & dosagem , Albuterol/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lactente , Isoproterenol/administração & dosagem , Isoproterenol/efeitos adversos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Resultado do Tratamento
9.
Pediatr Nephrol ; 34(5): 837-846, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30284023

RESUMO

BACKGROUND: Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. METHODS: This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. RESULTS: There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. CONCLUSIONS: We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. CLINICAL TRIAL REGISTRATION: Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .

10.
BMC Nephrol ; 19(1): 302, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382824

RESUMO

BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most common chronic glomerular disease in children. Approximately 80-90% of patients with childhood INS have steroid-sensitive nephrotic syndrome (SSNS), and can obtain remission with steroid therapy, while the remainder have steroid-resistant nephrotic syndrome (SRNS). Furthermore, approximately 50% of children with SSNS develop frequently-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS/SDNS are usually treated with immunosuppressive agents such as cyclosporine, cyclophosphamide, or mizoribine in Japan. However, 10-20% of children receiving immunosuppressive agents still show frequent relapse and/or steroid dependence during or after treatment, which is defined as complicated FRNS/SDNS. Furthermore, 30% of SRNS patients who obtain remission after additional treatments such as cyclosporine also turn out to be complicated FRNS/SDNS. For such complicated FRNS/SDNS patients, rituximab (RTX) is currently used; however, recurrence after RTX treatment also remains an open issue. Because long-term use of existing immunosuppressive drugs has limitations, development of a novel treatment for maintenance therapy after RTX is desirable. Mycophenolate mofetil (MMF) is an immunosuppressive drug with fewer side effects than cyclosporine or cyclophosphamide. Importantly, recent studies have reported the efficacy of MMF in children with nephrotic syndrome. METHODS: We conduct a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of MMF after RTX therapy in children with complicated FRNS/SDNS. Patients are allocated to either RTX plus MMF treatment group, or RTX plus placebo treatment group. For the former group, MMF is administered at a dose of 1000-1200 mg/m2/day (maximum 2 g/day) twice daily for 17 months after RTX treatment. The primary endpoint is time-to-treatment failure (development of frequent relapses, steroid dependence or steroid resistance). DISCUSSION: The results will provide important data on the use of MMF as maintenance therapy after RTX to prevent complicated FRNS/SDNS patients from declining into treatment failure. In future, MMF in conjunction with RTX treatment may permit increased duration of remission in 'complicated' FRNS/SDNS cases. TRIAL REGISTRATION: This trial was prospectively registered to UMIN Clinical Trials Registry on June 23, 2014 (UMIN Trial ID: UMIN000014347 ).


Assuntos
Fatores Imunológicos/administração & dosagem , Ácido Micofenólico/administração & dosagem , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/administração & dosagem , Esteroides/administração & dosagem , Criança , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Síndrome Nefrótica/fisiopatologia , Recidiva , Resultado do Tratamento
11.
BMC Nephrol ; 19(1): 223, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30200895

RESUMO

BACKGROUND: Eighty percent of children with steroid-sensitive nephrotic syndrome (SSNS) relapse within 2 years and 40-50% patients show frequently-relapsing nephrotic syndrome (FRNS). Patients showing a relapse within 6 months after initial remission are at high risk of FRNS. Since frequent prednisolone treatment for FRNS induces severe prednisolone side effects, development of a treatment to prevent patients from shifting to FRNS is desirable. Mizoribine is an immunosuppressive drug with fewer side effects than prednisolone. Recent studies reported the efficacy of high-dose mizoribine in children with FRNS. METHODS/DESIGN: We conduct a multicenter, open, randomized controlled trial to investigate the efficacy and safety of standard prednisolone plus high-dose mizoribine therapy in children with SSNS showing a relapse within 6 months after an initial remission. Patients are allocated to either standard prednisolone alone treatment group, or standard prednisolone plus high-dose mizoribine group. For the former group, mizoribine is administered at a dose of 10 mg/kg/day once daily and continued for 2 years. The primary endpoint is the duration to frequent relapse. DISCUSSION: The results provide important data on use of high-dose mizoribine to prevent SSNS patients from shifting to FRNS. Since blood concentrations of mizoribine have not been investigated in detail until now, there is a possibility that mizoribine is underestimated in favor of other immunosuppressive drugs. In future, high-dose mizoribine therapy may lead to prevention of relapse in children at high risk of FRNS, and to decreased total dose of prednisolone. TRIAL REGISTRATION: UMIN000005103 , (Prospectively registered 1st March 2011).


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Glucocorticoides/administração & dosagem , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Prednisolona/administração & dosagem , Ribonucleosídeos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Masculino , Recidiva , Esteroides/administração & dosagem
12.
Pediatr Nephrol ; 33(11): 2103-2112, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29987456

RESUMO

BACKGROUND: Two previous randomized controlled trials showed that treatment of severe childhood immunoglobulin A (IgA) nephropathy using prednisolone with azathioprine, heparin-warfarin, or dipyridamole prevented the increase of sclerosed glomeruli. Prednisolone alone, however, did not prevent further increase. These studies indicated the importance of immunosuppressants in the treatment. An additional pilot study using mizoribine instead of azathioprine enabled us to complete 2 years of combined regimen. It showed non-numerical inferior effectiveness compared with the azathioprine regimen. Further examination of the additional efficacy of warfarin and dipyridamole was required. METHODS: A randomized control trial of prednisolone and mizoribine with (group 1) or without (group 2) warfarin and dipyridamole was administered for treatment of 71 children with severe IgA nephropathy to evaluate the efficacy of additional warfarin and dipyridamole. RESULTS: Thirty of 34 patients (88.2%) in group 1, and 27 of 36 patients (75.0%) showed the disappearance of proteinuria as defined by early morning urinary protein to creatinine ratio of < 0.2 during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by the Kaplan-Meier method showed that the disappearance rate of proteinuria was significantly higher in group 1 than in group 2 (log-rank P = 0.04). There was no significant difference in pathological findings, but there was a tendency of increase of global sclerosis in group1 which might be related to warfarin. Most of the adverse effects were related to prednisolone, but fortunately transient. CONCLUSIONS: The balance between minimal benefits of warfarin/dipyridamole and potential adverse effects may be in favor of avoiding them in children with IgA nephropathy.


Assuntos
Dipiridamol/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Proteinúria/tratamento farmacológico , Varfarina/administração & dosagem , Adolescente , Biópsia , Criança , Dipiridamol/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/urina , Humanos , Imunossupressores/efeitos adversos , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/patologia , Proteinúria/urina , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento , Varfarina/efeitos adversos
14.
Pediatr Nephrol ; 33(9): 1449-1455, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28717938

RESUMO

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. A total of 80-90% of patients with childhood idiopathic nephrotic syndrome achieve remission with steroid therapy [steroid-sensitive nephrotic syndrome (SSNS)]. However, approximately 50% of children with SSNS develop frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Children with FRNS or SDNS are usually treated with immunosuppressive agents, but 10-20% of children receiving immunosuppressive agents still show frequent relapses or steroid dependence during or after treatment, defined as complicated FRNS or SDNS. Rituximab, a chimeric anti-CD20 monoclonal antibody that was originally developed to treat patients with B-cell non-Hodgkin's lymphoma, is currently used for treating SSNS. In this review we highlight recent studies, mainly randomized controlled trials of rituximab for SSNS, including complicated and uncomplicated forms of FRNS or SDNS in children. We also discuss the effects of these studies on the management of patients suffering from these conditions.


Assuntos
Glucocorticoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Antígenos CD20/imunologia , Antígenos CD20/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Criança , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do Tratamento
15.
Nephrology (Carlton) ; 23(6): 592-596, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28976051

RESUMO

Children with systemic lupus erythematosus (SLE) generally undergo a pretreatment kidney biopsy. However, some of these patients, especially those with antiphospholipid syndrome (APS), may experience serious coagulopathic complications. We report herein two cases of paediatric SLE with APS in which, despite normal blood test results, the disparate coagulopathic complications of haemorrhage and embolism developed following a kidney biopsy. Case 1 was, an 8-year-old male in whom, primary APS was initially diagnosed. Fourteen months later SLE was diagnosed. Based on a percutaneous kidney biopsy, International Society of Nephrology and the Renal Pathology Society (ISN/RPS) class III-A lupus nephritis was histologically diagnosed. On post-biopsy Day 9, a giant haematoma in the fascia of the left kidney developed and was accompanied by changes in the vital signs. Case 2, a 13-year-old male, initially received the diagnosis of SLE with APS and underwent two courses of pulse methylprednisolone therapy. His coagulation abnormalities improved, and a percutaneous needle kidney biopsy was performed, leading to the histological diagnosis of ISN/RPS class III-A lupus nephritis. Furthermore, thrombotic microangiopathy was also detected in the renal histopathology. On post biopsy Day 6, the patient experienced right leg pain. A contrast CT and lower extremity ultrasonography detected a massive deep vein thrombosis and partial left pulmonary artery thrombosis. A kidney biopsy in children with SLE and APS can cause lethal coagulopathic complications, and the risks to such patients should be weighed carefully before the procedure is performed.


Assuntos
Síndrome Antifosfolipídica/complicações , Arteriopatias Oclusivas/etiologia , Biópsia/efeitos adversos , Hematoma/etiologia , Rim/patologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/etiologia , Trombose Venosa/etiologia , Adolescente , Idade de Início , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/tratamento farmacológico , Coagulação Sanguínea , Criança , Glucocorticoides/uso terapêutico , Hematoma/sangue , Hematoma/diagnóstico , Hematoma/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/patologia , Masculino , Fatores de Risco , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico
16.
Am J Physiol Renal Physiol ; 313(6): F1223-F1231, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28877884

RESUMO

Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-ß/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-ß/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-ß, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-ß/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention.


Assuntos
Células Epiteliais/metabolismo , Rim/metabolismo , Rim Policístico Autossômico Recessivo/metabolismo , Proteína Smad3/metabolismo , Animais , Quinase 4 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Células Epiteliais/patologia , Predisposição Genética para Doença , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Rim/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Fosforilação , Rim Policístico Autossômico Recessivo/genética , Rim Policístico Autossômico Recessivo/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Proteína Smad3/deficiência , Proteína Smad3/genética
17.
Pediatr Nephrol ; 32(11): 2071-2078, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28664242

RESUMO

BACKGROUND: Although rituximab effectively prevents relapses of complicated frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS), data of long-term outcomes and safety are limited. METHODS: Fifty-one patients (age, 3-38 years) with childhood-onset complicated FRNS or SDNS, who received rituximab in investigator-initiated multicenter prospective trials were enrolled. Rituximab was administered at 375 mg/m2 once weekly for 4 weeks, and immunosuppressive agents were discontinued according to the study protocol. We investigated relapses, re-administration of immunosuppressive agents, additional rituximab treatment, body height, renal function, and late adverse events during the observation period. RESULTS: Forty-eight patients (94%) developed relapses during the observation period (median, 59 months) and the 50% relapse-free survival was 261 days. Thirty patients (59%) developed SDNS, 44 (86%) required re-administration of immunosuppressive agents, and 22 (43%) received additional rituximab treatment. All patients who were receiving immunosuppressive agents at rituximab treatment required either immunosuppressive agents or additional rituximab treatment. On the contrary, 5 of the 13 patients without immunosuppressive agents at rituximab treatment required neither immunosuppressive agents nor additional rituximab treatment and 3 of them did not develop relapse during observation period. Growth failure due to steroid toxicity did not progress and none of the patients developed chronic renal insufficiency. None of the patients suffered from rituximab-related late adverse events. CONCLUSIONS: As most patients suffer from relapses after B-cell recovery, long-term immunosuppressive agents or additional rituximab treatment is necessary. However, some patients who can discontinue immunosuppressive agents before rituximab treatment may achieve long-term remission after rituximab treatment without immunosuppressive agents.


Assuntos
Fatores Imunológicos/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Masculino , Síndrome Nefrótica/complicações , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Rituximab/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Clin Exp Nephrol ; 21(2): 193-202, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27422620

RESUMO

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.


Assuntos
Imunossupressores/uso terapêutico , Síndrome Nefrótica/congênito , Rituximab/uso terapêutico , Adolescente , Fatores Etários , Criança , Progressão da Doença , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/imunologia , Falência Renal Crônica/prevenção & controle , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/imunologia , Fatores de Risco , Rituximab/efeitos adversos , Resultado do Tratamento
19.
Pediatr Nephrol ; 32(3): 457-465, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27714465

RESUMO

BACKGROUND: Despite a low incidence, nephrotic syndrome (NS) can present with IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of pediatric patients with IgAN presenting with NS (NS-IgAN) at onset have not been fully elucidated. METHODS: We retrospectively analyzed 426 patients, and compared clinical and pathological (Oxford) findings between those with NS-IgAN and those with non-NS-IgAN. RESULTS: Among 426 patients, 30 (7.0 %) had NS-IgAN. Logistic analyses showed that male sex (OR: 7.6, p = 0.0002), M1 (OR: 10.3, p = 0.002), and E1 (OR: 15.2, p = 0.0001) were significantly related to NS. The mean observation period was 6.2 ± 3.2 years. Although NS-IgAN was associated with significantly lower renal survival than non-NS-IgAN according to Kaplan-Meier analysis (p = 0.02), renal survival of NS-IgAN was good (92.4 % at 10 years). The most significant prognostic factor for renal survival was remission of proteinuria after treatment, and NS at onset is also a significant prognostic factor for renal survival after adjusting for remission of proteinuria. Twenty children with NS-IgAN were treated with prednisolone alone, or prednisolone and immunosuppressant. Remission of proteinuria occurred in 21 patients. Three cases of NS-IgAN progressed to stage III-V chronic kidney disease at the most recent observation. They all demonstrated heavy proteinuria after the 2-year initial treatment. The significant factor for persistent proteinuria at 5 years was S1 in NS-IgAN. CONCLUSIONS: The most significant factor for renal survival was responsiveness to treatment, not NS itself. As modifiable acute lesions are the dominant pathological findings in NS-IgAN, histological improvements achieved by appropriate treatments can result in a favorable prognosis.


Assuntos
Glomerulonefrite por IGA/complicações , Síndrome Nefrótica/complicações , Idade de Início , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Rim/patologia , Falência Renal Crônica/etiologia , Masculino , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/patologia , Prednisolona/uso terapêutico , Prognóstico , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
Clin Exp Nephrol ; 20(6): 918-925, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26780894

RESUMO

BACKGROUND: Transition of adolescent and young adult (AYA) patients with childhood-onset chronic kidney diseases (C-CKD) from pediatric to adult renal services has received increasing attention. However, information on transition of Japanese patients with C-CKD is limited. METHODS: The Transition Medicine Working Group, in collaboration with the Japanese Society for Nephrology, the Japanese Society for Pediatric Nephrology and the Japanese Society of Pediatric Urology, conducted a retrospective cross-sectional study in 2014 on issues concerning the transition of Japanese patients with C-CKD. RESULTS: Few institutions in Japan had transition programs and/or transition coordinators for patients with C-CKD. Refusal to transfer by patients or their families, lack of concern about transition and inability to decide on transfer were common reasons for non-transfer of patients still followed by pediatric renal services. Around 25 % of patients who had ended or interrupted follow-up by pediatric renal services presented to adult renal services because of symptoms associated with C-CKD. Patients with various types of childhood-onset nephrourological diseases were transferred from pediatric to adult renal services. IgA nephropathy, minimal change nephrotic syndrome and congenital anomalies of the kidney and urinary tract were the most frequent primary kidney diseases in adult patients with C-CKD. CONCLUSION: These survey results indicate the need for introduction of transitional care for Japanese AYA patients with C-CKD. Consensus guidelines for the optimal clinical management of AYA patients with C-CKD are required to ensure the continuity of care from child to adult renal services.


Assuntos
Nefrologia , Pediatria , Insuficiência Renal Crônica/terapia , Adolescente , Adulto , Fatores Etários , Continuidade da Assistência ao Paciente , Estudos Transversais , Emprego , Humanos , Japão/epidemiologia , Educação de Pacientes como Assunto , Estudos Retrospectivos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA