RESUMEN
INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by a defective mitochondrial fatty acid oxidation (FAO) enzyme. We recently reported that bezafibrate improved patient quality of life (QOL) based on the SF-36 questionnaire score in patients with FAODs during a 50-week, open-label, clinical trial. Herein we conducted further survey assessments of the trial patients to define the long-term efficacy and safety of bezafibrate. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in five patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and one patient with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 15.9â¯years; range, 5.8-26.4â¯years). The bezafibrate administration was continued for a further 102-174â¯weeks after the 24-week treatment described in our previous study. QOL was quantitated using the 36-Item Short Form Health Survey (SF-36) questionnaire, which constitutes eight components: physical functioning (PF), role limitation due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitation due to emotional problems, and mental health. RESULTS: PF was elevated in all patients and continued to rise during the study, with the total QOL scores increased from baseline in five of the six cases. In particular, three patients older than 20â¯years showed treatment efficacy, and all subcategories of QOL were elevated in two of these cases. CONCLUSION: Our findings supported one of the stated benefits of bezafibrate in improving QOL for patients with FAODs.
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Aldosterona/sangre , Seudohipoaldosteronismo , Receptores de Mineralocorticoides/genética , Factores de Edad , Preescolar , Insuficiencia de Crecimiento/genética , Estudios de Asociación Genética , Humanos , Japón , Riñón/metabolismo , Pruebas de Función Renal/métodos , Masculino , Anamnesis , Mutación , Seudohipoaldosteronismo/sangre , Seudohipoaldosteronismo/diagnóstico , Seudohipoaldosteronismo/genética , Seudohipoaldosteronismo/fisiopatologíaRESUMEN
INTRODUCTION: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. MATERIALS AND METHODS: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8.2â¯years; ranging from 5.8 to 26.4â¯years). Bezafibrate was administered for 6â¯months following a 6-month observation period. The primary endpoint was the frequency of myopathic attacks, and the secondary endpoints were serum acylcarnitines (ACs, C14:1 or C16â¯+â¯C18:1), creatine kinase (CK) levels, degree of muscle pain (VAS; visual analog scale) during myopathic attacks, and quality of life (QOL; evaluated using validated questionnaires). RESULTS: The frequency of myopathic attacks after bezafibrate administration decreased in 3 patients, increased in 3, and did not change in 2. The CK, AC, and VAS values during attacks could be estimated in only three or four patients, but a half of the patients did not experience attacks before or after treatment. Changes in CK, AC, and VAS values varied across individuals. In contrast, three components of QOL, namely, physical functioning, role limitation due to physical problems (role physical), and social functioning, were significantly elevated. No adverse drug reactions were observed. CONCLUSION: In this study, the frequency of myopathic attacks and CK, AC, and VAS values during the attacks could not be evaluated due to several limitations, such as a small trial population. Our findings indicate that bezafibrate improves the QOL of patients with FAODs, but its efficacy must be examined in future investigations.
RESUMEN
BACKGROUND: The optimal long-term treatment for lupus nephritis (LN) in pubertal patients remains to be determined. Tacrolimus (Tac) inhibits T cell activation, and is therefore expected to be effective in patients with LN. However, little has been published about the long-term efficacy and safety of Tac-based immunosuppressive treatment of young patients with LN in daily clinical practice. METHODS: Nineteen consecutive patients with biopsy-proven LN were recruited for an open-label, prospective, long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as induction- or reinduction-maintenance treatment. Four patients (21%) with new-onset LN received mizoribine at a dose of 150 mg once daily in addition to Tac. Treatment outcomes were defined by the European Consensus Lupus Activity Measurement (ECLAM) index, urinary protein/creatinine ratio (Up/cr), serum creatinine and serological lupus markers (complement C3, complement hemolytic activity, CH50, and anti-dsDNA antibody titer). Data on these parameters were collected prospectively. The median follow-up was 42 months. RESULTS: Baseline characteristics of the patients were as follows: mean age, 18 years; Up/cr, 0.89 ± 1.17; serum C3, 68.1 ± 23.2 mg/dl (normal, 79-152 mg/dl); serum CH50, 26.4 ± 10.5 U/ml (normal, 23-46 U/ml); serum anti-dsDNA antibody titer, 69.3 ± 67.5 IU/ml (normal, <12.0 IU/ml); serum creatinine, 0.55 ± 0.18 mg/dl, and ECLAM index, 4.6 ± 1.9. Despite gradually tapering the dose of concomitantly administered prednisolone, a marked improvement compared with baseline values was observed in all outcome measures as early as 3 months after the initiation of treatment, and the favorable changes persisted throughout the treatment period in most of the patients. Sustained improvements in the outcome measures compared with the baseline values were confirmed after a mean of 42 months of treatment: ECLAM index, 1.1 ± 1.1; serum CH50, 36.0 ± 12.8 U/ml, anti-dsDNA antibody titer, 22.5 ± 26.5 IU/ml (all p < 0.01); Up/cr ratio, 0.35 ± 0.58, and serum C3 level, 79.7 ± 17.6 mg/dl (both p < 0.05). Serum creatinine level remained within the normal range in all the study participants. Complete response was achieved in 12 patients (63%), and a partial response was achieved in 5 patients (26%). The remaining 2 patients showed no response. No serious adverse effects were observed. CONCLUSION: The data suggest that long-term, relatively low-dose Tac-based immunosuppressive treatment is beneficial and has low cytotoxicity, and therefore represents an attractive option for the treatment of young patients with LN in daily clinical practice. Further studies involving a larger number of patients are needed to confirm these results.
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Inmunosupresores/administración & dosificación , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Tacrolimus/administración & dosificación , Adolescente , Niño , Método Doble Ciego , Femenino , Humanos , Japón , Estudios Longitudinales , Masculino , Resultado del TratamientoRESUMEN
A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.
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Artritis Juvenil/tratamiento farmacológico , Resistencia a Medicamentos , Glucocorticoides/administración & dosificación , Inmunoglobulinas Intravenosas/uso terapéutico , Metilprednisolona/administración & dosificación , Pericarditis/tratamiento farmacológico , Artritis Juvenil/complicaciones , Artritis Juvenil/diagnóstico , Niño , Ecocardiografía , Humanos , Masculino , Derrame Pericárdico/tratamiento farmacológico , Derrame Pericárdico/etiología , Pericarditis/diagnóstico , Pericarditis/etiología , Quimioterapia por Pulso , Índice de Severidad de la EnfermedadRESUMEN
Although recent reports suggest a possible role for an imbalance in Th1 and Th2 proinflammatory cytokines in the development and progression of glomerulonephritis, there is little information on Th1 or Th2 predominance in Henoch-Schönlein purpura nephritis (HSPN). Since T-bet and GATA-3 are transcriptional factors that regulate the differentiation of helper T lymphocytes into Th1 and Th2, we examined the relative mRNA expression of T-bet and GATA-3 in the urinary sediment of children with proteinuric HSPN by real-time quantitative PCR. Eight consecutive patients with proteinuric HSPN (4 with grade IIIa and 4 with grade IIIb according to the International Study of Kidney Disease in Children criteria) and 20 healthy subjects were enrolled in this study. The relative expression level of T-bet was significantly higher in the urinary sediment of patients with HSPN at presentation than in that of the healthy controls (p = 0.021), while the relative expression of GATA-3 was significantly lower in the urinary sediment of patients than in that of controls (p = 0.002). Urinary mRNA expression of T-bet correlated with the urinary protein/creatinine ratio (r = 0.608, p = 0.013), and correlated inversely with serum level of total protein (r = -0.574, p = 0.020). Moreover, a significantly increased intensity of T-bet immunostaining was observed in the glomeruli in the biopsy specimen of all study patients. All patients received immunosuppressive therapy. Repeat measurements of urinary mRNA expression of T-bet and GATA-3 after treatment revealed that the expression of T-bet in patients had significantly decreased relative to the baseline (p = 0.003), while the expression of GATA-3 remained static. In a patient subjected to a post-treatment renal biopsy, the increased intensity of immunostaining of T-bet had clearly diminished following immunosuppressive treatment, in accordance with a significant decrease in urinary mRNA expression of T-bet. These observations suggest that patients with proteinuric HSPN demonstrate increased T-bet and depressed GATA-3 expression in the urinary sediment, indicating a possible shift in Th1/Th2 balance towards Th1 predominance.
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Factor de Transcripción GATA3/análisis , Vasculitis por IgA/inmunología , Nefritis/inmunología , Proteínas de Dominio T Box/análisis , Células TH1/inmunología , Adolescente , Niño , Preescolar , Femenino , Factor de Transcripción GATA3/biosíntesis , Factor de Transcripción GATA3/inmunología , Humanos , Vasculitis por IgA/complicaciones , Vasculitis por IgA/metabolismo , Masculino , Nefritis/etiología , Nefritis/metabolismo , Proteinuria/etiología , Proteinuria/inmunología , Proteinuria/metabolismo , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas de Dominio T Box/biosíntesis , Proteínas de Dominio T Box/inmunologíaRESUMEN
An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac), mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported. We successfully treated 14 consecutive children with refractory CsA-resistant or CsA-intolerant NS using combination therapy consisting of relatively low-dose Tac, mizoribine (MZR), which has a mechanism of action very similar to that of MMF, and PDN. There were no serious clinical toxicities. Of the 14 children, 9 with a mean age of 13.0 years had steroid-dependent NS (SDNS) and 5 with a mean age of 9.6 years had steroid-resistant NS (SRNS). All SDNS patients had minimal change disease (MCD), 4 with SRNS had focal segmental glomerulosclerosis (FSGS), and the remaining child had MCD on renal biopsy. All patients were in a prospective cohort, but were evaluated retrospectively. The mean follow-up from the initiation of multidrug therapy was 18.4 months in SDNS and 18.6 months in SRNS patients. At the last observation point, the calculated relapse rate and minimum dose of PDN required for maintenance of clinical remission after the start of multidrug therapy were significantly decreased compared with those prior to this therapy, while on CsA, in SDNS patients (0.4 ± 0.5 times/year vs 2.9 ± 1.5 times/year, P = 0.0077, and 0.3 ± 0.2 mg/kg on alternate days vs 0.5 ± 0.2 mg/kg on alternate days, P = 0.0184 respectively). All SDNS and two SRNS patients (40%) achieved complete remission, allowing further decreases in the minimal doses of PDN required for maintenance of clinical remission in most our patients. However, one patient with FSGS remained refractory to multidrug therapy and subsequently developed end-stage renal disease. These clinical observations, although preliminary and involving a small number of patients, suggest that multidrug therapy consisting of relatively low-dose Tac, MZR, and PDN might be effective and safe for treating children with refractory CsA-resistant or CsA-intolerant NS. However, further studies involving larger numbers of patients are needed.
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Inmunosupresores/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Prednisona/administración & dosificación , Ribonucleósidos/administración & dosificación , Tacrolimus/administración & dosificación , Adolescente , Niño , Ciclosporina/uso terapéutico , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Masculino , Proyectos Piloto , Adulto JovenAsunto(s)
Resistencia a Medicamentos , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ribonucleósidos/uso terapéutico , Esteroides/uso terapéutico , Adolescente , Biopsia , Femenino , Glomerulonefritis Membranoproliferativa/patología , Humanos , Resultado del TratamientoAsunto(s)
Antiinflamatorios/uso terapéutico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Diarrea/complicaciones , Síndrome Hemolítico-Urémico/tratamiento farmacológico , Inmunoglobulinas Intravenosas/administración & dosificación , Metilprednisolona/administración & dosificación , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/etiología , Enfermedades del Sistema Nervioso Central/inmunología , Preescolar , Trastornos de la Conciencia/tratamiento farmacológico , Trastornos de la Conciencia/etiología , Diarrea/microbiología , Escherichia coli/aislamiento & purificación , Femenino , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/etiología , Síndrome Hemolítico-Urémico/inmunología , Humanos , Mediadores de Inflamación/metabolismo , Imagen por Resonancia Magnética , Quimioterapia por Pulso , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase involved in immune reactions against RNA viruses and various inflammatory and autoimmune diseases. The purpose of the present study was to investigate the role of RIG-I in glomerular diseases. METHODS: We treated human mesangial cells in culture with polyinosinic-polycytidylic acid (poly IC), which is an authentic double-stranded RNA, and analysed the expression of RIG-I, CC chemokine ligand 5 (CCL5) and interferon (IFN)-ß by western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) or enzyme-linked immunosorbent assay (ELISA). To elucidate the poly IC-signalling pathway, we subjected the cells to RNA interference (RNAi) against RIG-I, IFN-ß or Toll-like receptor (TLR) 3. Furthermore, we studied the effects of IFN-ß receptor blocking and IFN-ß overexpression. RESULTS: Poly IC induced the expression of RIG-I and CCL5 in human mesangial cells, and RNAi against RIG-I inhibited this poly IC-induced CCL5 expression. Poly IC-induced RIG-I expression was also inhibited by RNAi against IFN-ß and by an antibody against the IFN-ß receptor. IFN-ß overexpression induced the expression of both RIG-I and CCL5. The knockdown of TLR3 abolished poly IC-induced RIG-I expression. CONCLUSIONS: The TLR3/IFN-ß/RIG-I/CCL5 signalling pathway may mediate immune and inflammatory responses against viral infection in mesangial cells, suggesting the role of this pathway in the aggravation of glomerulonephritis due to viral infection.
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Quimiocina CCL5/genética , ARN Helicasas DEAD-box/fisiología , Regulación de la Expresión Génica , Células Mesangiales/inmunología , ARN Bicatenario/farmacología , Células Cultivadas , Proteína 58 DEAD Box , ARN Helicasas DEAD-box/genética , Dexametasona/farmacología , Humanos , Interferón beta/fisiología , Poli I-C/farmacología , ARN Interferente Pequeño/genética , Receptores Inmunológicos , Receptor Toll-Like 3/fisiologíaRESUMEN
The purine synthesis inhibitor mizoribine (MZR) has been successfully used without serious adverse effects in the treatment of several renal diseases including lupus nephritis. Besides its immunosuppressive effects, MZR has recently been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration. However, there has been little information regarding the beneficial effects of MZR from the histologic standpoint in human lupus nephritis. Pre- and posttreatment renal biopsy specimens obtained from nine patients with diffuse proliferative lupus nephritis (DPLN) were divided into two groups (group A, five patients who received immunosuppressive treatment with MZR and group B, four patients who received immunosuppressive treatment without MZR) and histologically evaluated. Grading was done according to the 2003 classification system for lupus nephritis developed by the International Society of Nephrology/Renal Pathology Society, which considers the activity and chronicity indices, an immunohistologic study to assess intraglomerular and interstitial infiltration by macrophages, and the expression of osteopontin. Although in all the patients the posttreatment renal biopsy showed improvement of histologic grading and activity indices, group A patients showed a significant decrease of the chronicity indices and of intraglomerular infiltration by macrophages when compared to group B patients (2.6 +/- 0.5 vs 4.0 +/- 1.4 and 0.5 +/- 0.2 vs 2.4 +/- 1.9 cells per glomerulus, respectively; p < 0.05). Although this was a preliminary study in a small number of subjects, these histological observations may further confirm the beneficial effects of MZR for selected patients with DPLN.
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Movimiento Celular/efectos de los fármacos , Riñón/patología , Nefritis Lúpica/patología , Macrófagos/patología , Ribonucleósidos/farmacología , Índice de Severidad de la Enfermedad , Adolescente , Biopsia , Niño , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Nefritis Lúpica/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Masculino , Insuficiencia Renal/prevención & control , Ribonucleósidos/uso terapéuticoAsunto(s)
Glomerulonefritis por IGA/sangre , Adolescente , Niño , Femenino , Factor de Transcripción GATA3/orina , Glomerulonefritis por IGA/patología , Humanos , Riñón/patología , Glomérulos Renales/patología , Masculino , Proteínas de Dominio T Box/orina , Células TH1/metabolismo , Células Th2/metabolismoRESUMEN
Cyclosporine A (CsA) is an effective steroid-sparing agent for patients with steroid-dependent, relapsing nephrotic syndrome (SDRNS). The efficacy and safety of single-daily dose administration (SDD protocol) of CsA in selected patients with SDRNS has been reported. However, the efficacy of initial CsA treatment for children with SDRNS using the SDD protocol remains to be elucidated. The SDD protocol might be associated with lower clinical toxicity, compared to the conventional twice-daily dose administration (TDD protocol). Here we evaluated the efficacy and safety of the SDD protocol versus the TDD protocol in patients with SDRNS. The data from 19 patients (9.9 +/- 4.2 years old) were retrospectively collected and analyzed. Ten patients treated according to the SDD protocol for a mean of 27 months (SDD group), while 9 patients treated with the TDD protocol for a mean of 35 months (TDD group) as an initial CsA treatment. Although the mean daily CsA dose was significantly lower in the SDD group (1.5 +/- 0.4 mg/kg/day vs. 3.7 +/- 0.7 mg/kg/day, P < 0.01), there were no differences between the two groups in the mean minimum dose of prednisolone required for maintenance of clinical remission nor in the calculated relapse rate. One patient in the TDD group developed biopsy-proven mild CsA nephrotoxicity, whereas no patient in the SDD group showed nephrotoxicity. Despite a small number of patients, this study may support that the SDD protocol is at least as effective as the conventional TDD protocol, and is more cost-effective for selected children with SDRNS.
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Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Adolescente , Niño , Preescolar , Ciclosporina/farmacología , Esquema de Medicación , Femenino , Humanos , Inmunosupresores/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Albúminas/uso terapéutico , Síndrome Nefrótico/sangre , Albúminas/genética , Niño , Ensayos Clínicos como Asunto , Diuréticos/uso terapéutico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Furosemida/uso terapéutico , Humanos , Proyectos Piloto , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
A proportion of patients with refractory nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) often require long-term hospitalization, which results in the loss of quality of life (QOL) of the patients. An-11-year-old girl was brought to a regional hospital with an 8-day history of generalized edema. Laboratory studies revealed massive proteinuria without hematuria and marked hypoalbuminemia associated with hyperlipidemia. A percutaneous renal biopsy revealed lesions characteristic of FSGS. Although methylprednisolone pulse therapy was administered followed by oral prednisolone combined with cyclosporine A, heavy proteinuria persisted for the next 4 months. The patient was referred subsequenthy to our hospital for further examinations. High-dose intermittent mizoribine pulse therapy, LDL-apheresis, cyclosporine A, tacrolimus and intravenous cyclophosphamide pulse therapy proved to be partially effective. As a result, long-term hospitalization and intravenous administration of albumin, diuretics and immunoglobulin was required for this patient. Also, she developed severe steroid toxicity such as obesity, cataract and osteoporosis. A third renal biopsy revealed an advanced stage of FSGS lesions, suggesting subsequent development of end-stage renal disease (ESRD). Since the patient suffered from long-term hospitalization over 3 years and significant loss of QOL, we therefore proposed early initiation of peritoneal dialysis (PD), as in cases of congenital NS, in order to preserve the patient's general condition without intravenous drug administrations and for the preparation of a future renal transplantation. After obtaining informed consent from the patient and her family, the initiation of PD was performed at the age of 15 years before the ESRD state(serum creatinine level 2.0 mg/dL). The patient was successfully free from intravenous drug administrations and hospitalization, and the QOL was significantly improved thereafter. We, therefore, suggest that early initiation of PD might be a treatment of choice for elected patients with severe refractory nephrotic syndrome such as this presented case.
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Síndrome Nefrótico/terapia , Diálisis Peritoneal , Calidad de Vida , Adolescente , Femenino , Humanos , Fallo Renal Crónico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Resistencia a Medicamentos/efectos de los fármacos , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Prednisolona/uso terapéutico , Tacrolimus/uso terapéutico , Niño , Preescolar , Ciclosporina/farmacología , Quimioterapia Combinada , Glomeruloesclerosis Focal y Segmentaria/patología , Humanos , Masculino , Ácido Micofenólico/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: A novel purine synthesis inhibitor, mizoribine (MZR), with a similar activity to that of mycophenolate mofetil, was developed in Japan. We suspected that long-term oral MZR intermittent pulse therapy (MZR-P) might be more effective than the conventional daily MZR regimen due to the higher peak serum MZR levels that are achieved. Here, we examined the clinicopathologic efficacy of MZR-P treatment in 10 young patients with diffuse proliferative lupus nephritis (DPLN), including 3 patients who received MZR-P as their primary cytotoxic therapy. METHODS: After their most recent renal flare-ups, all the patients were treated using MZR-P combined with oral prednisolone (PDN). MZR was administered as a single daily dose of 6-10 mg/kg per day (maximum dose of 500 mg) on 2 days of the week (Monday and Thursday) for at least 12 months or longer. The concomitantly administered PDN dose was gradually reduced. RESULTS: The baseline characteristics of the patients were as follows: mean age 15 years; urinary protein/creatinine (Up/cr) ratio 1.57 +/- 1.05 mg/mg; serum C3 level 50.3 +/- 19.7 mg/dl; serum complement hemolytic activity (CH50) 18.1 +/- 9.9 U/ml; serum anti-dsDNA antibody titer 177.5 +/- 152.7 IU/ml; serum creatinine 0.6 +/- 0.1 mg/dl, and European Consensus Lupus Activity Measurement (ECLAM) index 4.9 +/- 2.6. Despite the gradual tapering of the PDN dose, marked improvements compared with the baseline values were observed at the last observation, mean interval of 29 months after the start of treatment: Up/cr ratio 0.19 +/- 0.14; ECLAM index 1.3 +/- 0.7 (p < 0.01); serum C3 level 76.5 +/- 22.1 mg/dl; serum CH50 value 31.9 +/- 8.7 U/ml, and anti-dsDNA antibody titer 34.2 +/- 20.5 IU/ml (p < 0.05). The serum creatinine level remained within the normal range in all study participants. Post-treatment renal biopsies were performed in 5 of the patients; histology showed a marked attenuation of lesion progression. No serious adverse effects were observed. CONCLUSION: We believe that long-term MZR-P may prove to be a treatment of choice for young patients with DPLN. However, confirmation is needed as this preliminary study is limited by the small number of subjects, lack of controls, and its retrospective nature.
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Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Ribonucleósidos/administración & dosificación , Administración Oral , Adolescente , Niño , Femenino , Humanos , Inmunosupresores/administración & dosificación , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Henoch-Schönlein purpura (HSP) is a childhood disorder, which is the vasculitis of systemic small vessels of unknown etiology. We encountered the dramatic efficacy of leukocytapheresis in a Japanese girl with refractory HSP resistant to combined prednisolone plus intravenous immunoglobulin therapy administration.