Huangkui capsule in combination with leflunomide improves immunoglobulin a nephropathy by inhibiting the TGF-ß1/Smad3 signaling pathway.

OBJECTIVES: To investigate the efficacy and potential molecular mechanism of Huangkui capsule in combination with leflunomide (HKL) for the treatment of immunoglobulin A nephropathy (IgAN) METHODS: IgAN rat models were constructed by treating rats with bovine serum albumin, lipopolysaccharide, and tetrachloromethane. Th22 cells were isolated from the blood samples of patients with IgAN using a CD4+ T cell isolation kit. The expression levels of the components of the TGF-β1/Smad3 signaling pathway, namely, TGF-β1, Smad2, Smad3, Smad4, and Smad7, were detected using quantitative reverse transcription polymerase chain reaction. Cell proliferation was determined using the MTT assay, cell viability was determined using the WST 1 method, and the chemotaxis of Th22 cells was observed using the wound healing assay. Changes in the histology of the kidney tissues were analyzed using hematoxylin and eosin staining. RESULTS: Compared with IgAN rats, the rats subjected to HKL treatment showed good improvement in kidney injuries, and the combined drug treatment performed much better than the single-drug treatment. In addition, following HKL treatment, the viability, proliferation, and chemotaxis of Th22 cells dramatically decreased (*p<0.05, **p<0.01, and ***p<0.001). In addition, CCL20, CCL22, and CCL27 levels decreased and the expression of the key components of the TGF-β1/Smad3 signaling pathway was downregulated in IgAN rats and Th22 cells (*p<0.05, ***p<0.001). CONCLUSIONS: By targeting the TGF-β1/Smad3 signaling pathway, HKL treatment can improve kidney injury in IgAN rats as well as the excessive proliferation and metastasis of Th22 cells.

Acute renal failure by rapidly progressive glomerulonephritis with IgA deposition in a patient concomitantly diagnosed with multibacillary Hansen's disease: a case report / IRA por glomerulonefrite rapidamente progressiva com depósito de IgA em uma paciente com diagnóstico concomitante de hanseníase multibacilar: relato de caso

ABSTRACT Rapidly progressive glomerulonephritis (RPGN) is a renal disease with an extensive differential diagnosis. This paper reports the case of a 55-year-old female patient diagnosed with Hansen's disease with acute progressive renal impairment after developing lower limb pyoderma. The association between Hansen's and kidney disease has been well documented, with glomerulonephritis (GN) ranked as the most common form of renal involvement. Post-infectious glomerulonephritis (PIGN) in adults has been associated with a number of pathogens occurring in diverse sites. The patient described in this case report had RPGN and biopsy findings suggestive of PIGN with C3 and IgA detected on immunofluorescence and kidney injury secondary to recent infection by Staphylococcus, a well-documented manifestation of renal impairment in patients with Hansen's disease.

RESUMO A Glomerulonefrite Rapidamente Progressiva (GNRP) é um padrão de doença renal com amplo diagnóstico diferencial. O caso reporta uma paciente de 55 anos com deterioração aguda e progressiva da função renal após quadro de piodermite em membro inferior com diagnóstico concomitante de hanseníase. Associação da hanseníase com doença renal é bem descrita, sendo a GN a forma de acometimento renal mais comum. As glomerulonefrites pós-infecciosas (GNPIs) em adultos ocorrem devido a um grande número de patógenos, nos mais diversos sítios. A paciente do caso relatado apresentava quadro de GNRP e achados de biópsia que sugerem GNPI com marcação de C3 e IgA na imunofluorescência, sugestiva de lesão renal secundária a infecção recente por Staphylococcus, uma manifestação bem descrita de doença renal em pacientes com hanseníase.

Relato de Caso - Nefropatia de IgA associada ao ANCA com evolução favorável / Case report - IgA nephropathy ANCA positive with favorable outcome

ResumoIntrodução:Os anticorpos anticitoplasma de neutrófilos (ANCA) comumente estão relacionados a glomerulonefrites rapidamente progressivas (GnRP) com padrão pauci-imune. Apesar disso, a literatura mostra uma incidência além da esperada de ANCA nas GnRP por imunocomplexos. A nefropatia por imunoglobulina A (NIgA) crescêntica é uma das GnRP que pode se associar ao ANCA.Objetivo:Relatar caso de NigA com sinais clínicos de mau prognóstico associado ao ANCA com evolução favorável após imunossupressão.Método:Foi relatado caso de paciente com 38 anos com quadro de hipertensão arterial (HAS), insuficiência renal (CKD-EPI- 37 ml/min/1,73 m2), proteinúria subnefrótica e hematúria. Nos antecedentes pessoais, relatava epistaxes ocasionais, rinossinusite e episódio de artrite com remissão espontânea. Durante a investigação diagnóstica, foram detectados ANCA positivo 1/160 e anti-PR3, porém, com biópsia renal compatível com NIgA com 38% de crescentes na amostra. Foi realizado diagnóstico de NIgA associada ao ANCA, sendo indicado tratamento imunossupressor por seis meses com corticoterapia (pulsoterapia com metilprednisolona 1 g por 3 dias, seguido de prednisona 1 mg/kg/dia) e ciclofosfamida (500 mg com aumento crescente da dose até 750 mg/m2). Paciente evolui com recuperação da função renal, além da redução da proteinúria e da titulação de ANCA.Conclusão:A importância da identificação dessa sobreposição está no comportamento agressivo dessa doença caracterizada pela presença de crescentes, atrofia tubular e disfunção renal que podem regredir com início precoce da imunossupressão.

AbstractIntroduction:The antineutrophil cytoplasmatic antibody (ANCA) is usually associated with pauci-immune crescentic glomerulonephritis (CrGN). However, the literature show an incidence unexpected high of ANCA in immunocomplex CrNP. The crescent IgA nephropaty is one of CrGN that associated with ANCAObjective:To relate an IgA nephropaty ANCA positive and sign of worse prognosis that improved with immunossupression.Method:38-year-old pacient with arterial hypertension, renal impairment (CKD-EPI 37 ml/min/1,73 m2), non-nephrotic proteinuria and hematuria. He related occasionally epistaxis, rhnosinusitis and one arthritis episode that spontaneously resolved. During de investigation, the ANCA titles were 1/160 and anti-RP3 was positive, however renal biopsy showed IgA nephropaty with 38% of crescents. Regarding IgA nephropaty ANCA positive as the main diagnosis, immunossupression therapy with corticoids (1g IV methilprednisone for 3 days followed by 1 mg/kg/day prednisone) for 6 months and cyclophosphamide (500 mg initially then raise the dose until reach 750 m2. The patient improved renal function and reduced the proteinuria and ANCA titulation.Conclusion:The role of the association between IgA nephropathy and ANCA is it aggressive manifestation characterized by the presence of crescents, tubular atrophy and renal dysfunction, which may regress with early onset of immunosuppression treatment.

Corticotherapy response in primary IgA nephropathy / Resposta à corticoterapia na nefropatia da IgA primária

INTRODUCTION: Some beneficial effects from long-term use of corticosteroids have been reported in patients with IgA nephropathy. OBJECTIVE: This retrospective study aimed to evaluate the outcome of proteinuria and renal function according to a protocol based on a 6-month course of steroid treatment. METHOD: Twelve patients were treated with 1 g/day intravenous methylprednisolone for 3 consecutive days at the beginning of months 1, 3, and 5 plus 0.5 mg/kg oral prednisone on alternate days for 6 months (treated group). The control group included 9 untreated patients. RESULTS: Proteinuria (median and 25th and 75th percentiles) at baseline in the treated group was 1861 mg/24h (1518; 2417 mg/24h) and was 703 mg/24h (245; 983) and 684 mg/24h (266; 1023) at the 6th (p < 0.05 vs. baseline) and 12th months (p < 0.05 vs. baseline), respectively. In the control group the proteinuria was 1900 mg/24h (1620; 3197) at baseline and was 2290 mg/24h (1500; 2975) and 1600 mg/24h (1180; 2395) at the 6th and 12th months, respectively (not significant vs. baseline). When compared with the control group, the treated group showed lower proteinuria (p < 0.05) during the follow-up and a higher number of patients in remission (p < 0.05) at the 6th and 12th months. Renal function did not change during the follow-up and the adverse effects were mild in most of the patients. CONCLUSION: The 6-month course of steroid treatment was effective in reducing proteinuria during the 12 months of the follow-up, and was well-tolerated by most of the patients.

INTRODUÇÃO: Tem sido sugerido que tratamento mais prolongado com corticosteroides pode ser benéfico em pacientes com nefropatia da IgA primária. OBJETIVO: Neste estudo retrospectivo avaliamos os efeitos na proteinúria e na função renal após 12 meses do protocolo baseado no uso por 6 meses de corticosteroides. MÉTODO: Doze pacientes receberam pulsos de 1 g/dia de metilprednisolona intravenosa por 3 dias consecutivos no início dos meses 1, 3 e 5, seguidos por prednisona (0,5 mg/kg) por via oral em dias alternados após cada pulso durante 6 meses (grupo tratado). O grupo controle foi composto por nove pacientes não tratados. RESULTADOS: A proteinúria (mg/24h; mediana; 25º; 75º percentis) no período basal no grupo tratado foi de 1861 (1518; 2417) e de 703 (245; 983) e de 684 (266; 1023) nos 6º (p < 0,05 vs. basal) e 12º (p < 0,05 vs. basal) meses, respectivamente. No grupo controle, a proteinúria foi de 1900 (1620; 3197) no período basal e de 2290 (1500; 2975) e de 1600 (1180; 2395) nos 6º e 12º meses, respectivamente (não significantes vs. basal). Comparado com o grupo controle, o grupo tratado teve menor proteinúria (p < 0,05) e número maior de pacientes em remissão (p < 0,05) nos 6º e 12º meses. A função renal não teve alteração significante e eventos adversos foram de pequena intensidade na maioria dos pacientes. CONCLUSÃO: O protocolo terapêutico base-ado no uso por 6 meses de corticosteroides foi efetivo em reduzir a proteinúria durante os 12 meses de seguimento e foi bem tolerado pela maioria dos pacientes.

Hereditary spherocytosis with immunoglobulin a nephropathy

Hereditary spherocytosis is a familial hemolytic anemia. Immunoglobulin A [IgA] nephropathy associated with hereditary spherocytosis has not been reported in children. Here, we report a case of a 17-year-old boy with IgA nephropathy and hereditary spherocytosis. The patient was diagnosed with hereditary spherocytosis at the age of 12 years and splenectomy was done at the age of 15 years. Later, the patient presented with macroscopic hematuria and proteinuria. Kidney biopsy of the boy was consistent with IgA nephropathy. Treatment with angiotensin-converting enzyme inhibitor was started. The patient became free of proteinuria after the 6th month of therapy

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy / Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria more than 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 more or less 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 more or less 1.86 g/day; serum creatinine 1.07 more or less 0.29 mg/dl; mean follow-up 60.10 more or less 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 more or less 0.07 g/day (P less than 0.001) while serum creatinine did not vary: 1.07 ± 0.28 mg/dl (P=ns). After a mean follow-up of 42.36 more or less 21.56 months urinary protein excretion (0.12 more or less 0.06 g/day) and renal function (serum creatinine 1.06 more or less 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to less than 0.5 g/day in patients with IgA nephropathy without changes in renal function.

El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias major que 0.5 g/día y creatininas séricas menor que 1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a menor que 0.5 g/día. Fueron incluidos 20 pacientes: Edad: 37.45 más o menos 13.3 años (50% hombres); 7 pacientes (35%) eran hipertensos; proteinuria inicial 2.2 más o menos 1.86 g/día; creatinina inicial 1.07 más o menos 0.29 mg/dl; seguimiento promedio: 60.10 más o menos 31.47 meses (5 más o menos 2.62 años). La nefropatía por IgA fue subclasificada según Haas: 12 pacientes (60%) clase II; 7 (35%) clase III y 1 (5%) clase V. Todos recibieron enalapril más valsartán según tolerancia más metilprednisona vía oral en dosis de 0.5 mg/kg/día durante las primeras 8 semanas y subsecuentemente se redujo cada dos semanas hasta llegar a 4 mg. Se discontinuaron los esteroides luego de 24 semanas (6 meses). La inhibición del sistema renina angiotensina prosiguió indefinidamente. A las 10 semanas la proteinuria disminuyó de 2.2 más o menos 1.86 g/día a 0.15 más o menos 0.7 g/día (p menor que 0.001); la creatinina no varió significativamente (1.07 más o menos 0.29 mg/dl vs. 1.07 más o menos 0.28 mg/dl) (P=ns). Luego de 10 semanas y con un seguimiento de 42.36 más o menos 21.56 meses la proteinuria (0.12 más o menos 0.006 g/día) y la función renal (creatinina 1.06 más o menos 0.27mg/dl) permanecieron estables. No se informaron efectos adversos durante el estudio. El doble bloqueo del sistema renina angiotensina más bajas dosis de metilprednisona resultó útil para reducir...

The effect of alpha-tocopherol on the oxidative stress and antioxidants in idiopathic IgA nephropathy.

OBJECTIVE: Nearly 25% of IgA nephropathy patients progress to end-stage renal disease over a 20-25 year follow-up period. IgA containing immune complex stimulates oxygen free radical production by mesangial cells in vitro, which may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal damage in patients with IgA nephropathy. MATERIAL AND METHOD: Twenty-eight patients with idiopathic IgA nephropathy were supplemented with vitamin E 400 mg/day for 6 months. Antioxidant enzymes, glutathione, plasma malondialdehyde (MDA), and renal function were studied after 3 and 6 months therapy. RESULT: The result of the study showed high plasma MDA and significant reduction after therapy (1.15 +/- 0.45 VS 0.86 +/- 0.30 microM, p < 0.0001). The RBC vitamin E was also elevated statistically significantly (5.07 +/- 2.42 VS 15.70 +/- 3.37 microM, p < 0.001). Glutathione peroxidase activities were decreased (38.52 +/- 15.53 VS 23.97 +/- 7.63 U/gHb, p < 0.001). Glutathione was also decreased (44.80 +/- 9.70 VS 32.45 +/- 6.74 mg/dl, p < 0.05) but there were no changes in red cell catalase and superoxide dismutase activities. Creatinine clearance, proteinuria, urine N-acetyl glucosaminidase and beta2-microglobulin also showed no improvement. CONCLUSION: Our data demonstrated the particular group of IgA nephropathy patients with low vitamin E level and high oxidative stress had significant reduction of oxidative stress after vitamin E therapy.

Survival analysis of Thai patients with IgM nephropathy, focal segmental glomerulosclerosis and membranous nephrotic syndrome.

Long term outcome of 124 Thai adult nephrotic patients was determined. Nephrotic syndrome affects the young more often than the old (median age 29 years). The most common pathology was IgM nephropathy (45.2%), membranous nephropathy (31.5%) and FSGS (23.4%). Sixty-four per cent of patients with IgM nephropathy respond to corticosteroid within 4-8 weeks while twenty three per cent were late responders. However, more than half of these patients were relapsers or steroid dependent. Response to corticosteroid occurred in 48.2 per cent of patients with FSGS while the response rate of patients with membranous nephropathy was only 23.1 per cent. Survival analysis revealed that five and ten years renal survival of IgM nephropathy was 98 per cent. Five and ten years renal survival of FSGS was 83.7 per cent and 76.8 per cent while those of membranous nephropathy was 95 per cent and 63.3 per cent. The response to corticosteroid was associated with better prognosis in FSGS. Our results show that patients with IgM nephropathy and membranous nephropathy have a generally good prognosis. Renal function is usually well preserved for at least ten years. The prognosis of patients with FSGS varied and correlated with the degree of steroid responsiveness.

Hipotiroidismo autoinmune asociado a nefropatía por IgA

La nefropatía por IgA, cuya incidencia en la población pediátrica oscila entre 1.5 y 56.21 según reportes publicados en el sur de Europa, Australia y Japón, se reporta como primera causa de glomerulonefritis primaria en niños. La nefropatía por IgA puede ser primaria o secundaria, se diagnostica por demostración de IgA predominantemente mesangial o IgA codominante en el glomérulo sin evidencia de lupus eritematoso. La mayoría de los pacientes presenta hematuria macroscópica y el pronóstico depende de los marcadores genéticos y la severidad de la lesión histológica renal. A continuación presentamos el reporte de un caso de una paciente con evidencia de hipotiroidismo primario autoinmune y nefropatía por IgA.

Effect of captopril on heavy proteinuria in patients with various glomerular diseases

The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p< 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p< 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.

Enfermedad de Berger / Berger's disease

De 33 pacientes que asistieron a consulta por presentar hematuria macroscópica recurrente, microscópica persistente o ambas, 8 de ellos fueron diagnosticados con nefropatía con depósitos de inmunoglobulina A (IgA) utilizando el estudio por inmunofluorescencia de las muestras tomadas mediante la biopsia renal. Las edades de los pacientes fluctuaron entre 5 y 14 años; 6 fueron del sexo masculino. Se precisó antecedente prodrómico de infección respiratoria o digestiva previo a la crisis de hematuria macroscópica y 6 pacientes mostraron IgA sérica elavada. En 2 familias estudiadas se halló en el suero de la madre de 1 de los casos la IgA elevada. Al estudio por el microscopio òptico, 5 pacientes tuvieron lesiones clasificadas como daño mínimo: 2, lesiones proliferativas mesangiales y en 1 caso se comprobó esclerosis segmentaria focal. Se hizo un ensayo terapéutico con levamisol en dosis de 2,5 mg/kg/d durante 3 días consecutivos de la semana y en la mayor parte de los casos se modificó la evolución, aunque después de 2 años de observación no se pudo concluir que los mismos estaban curados

Nefropatia mesangial primária da IgA (doença de Berger): estudo clínico-patológico / Primary IgA mesangial nephropathy (Berger's disease): clinico-pathological study

Quarenta pacientes com nefropatia mesangial primária da IgA internados no Hospital das Clínicas da FMUSP, entre 1976 e dezembro de 1984 foram estudados dos pontos de vista clínico e patológico. A incidência da moléstia, pesquisada para o ano de 1984, foi da ordem de 6,5% do total de casos de glomerulopatias primárias biopsiadas nesse ano. Dos 40 pacientes, 27(67,5%) eram do sexo masculino. As manifestaçöes clínicas da doença se iniciaram entre 11 e 30 anos de idade em 29 caos (72,5%). Quanto à cor, 33 doentes (82,5%) eram brancos, 4 (10%) amarelos e 3 (7.5%) pardos. A apresentaçäo clínica da nefropatia foi de hematúria macroscópica no transcurso de processos infecciosos agudos em 25 pacienes (62,5%), proetinúria e hamatúria microscópica em 5 casos (12,5%), insuficiência renal crónica em 5 casos (12,5%) e síndrome nefrítica aguda em 3 casos (7,5%). Um paciente apresentou hematúria macroscópica näo relacionada a processos infecciosos ou esforços físicos e outro teve quadro clínico recidivante que simulava infecçöes urinárias agudas. Por ocasiäo da biopsia renal, hematúria estava presente em 100% dos casos e proteinúria, em 92,5%. A depuraçäo de creatinina, avaliada em 39 doentes, estava acima de 90 ml/min/ 1,73m2 em 28 (70%, entre 50 e 89 em 3 (7,5%) e abaixo de 25 em 8 (20%). O complemento total CH2 mostrva leve reduçäo em 20,6% dos pacientes avaliados, a fraçäo C3 também evidenciava queda discreta em 9,5% e a fraçäo C4 foi encontrada sempre normal. A IgA sérica estava elevada em 4(21%) de 19 casos. Os imune-complexos circulantes estiveram sempre dentro dos limites da normalidade. A biosia renal revelou proliferativas mesangiais focais em 17 pacientes (42,5%) e difusas em 16(40%). Seis doentes (15%) tinham lesöes mínimas e um, a forma crescêntica. A imunofluorescência revelou depósitos mesangiais granulares de distribuiçäo global e difusa em todos os pacientes, com presença de IgA predominante nos 40 casos (100%), C3 em 40 doentes (100%), IgG em 34 (85%), IgM em 13(32,5%) e fibronogênio em 4(10%)...