Falta de adherencia al control médico en pacientes pediátricos con antecedente de glomerulonefritis infecciosa

Introducción: La glomerulonefritis pos infecciosa (GNPI) en la infancia es un factor de riesgo para el desarrollo de enfermedad renal crónica a largo plazo. La adherencia al control médico permite realizar la nefroprevención secundaria. Objetivo: evaluar la relación entre los factores de riesgo relacionados a la falta de adherencia al control médico de pacientes con GNPI en una cohorte pediátrica. Metodología: estudio descriptivo de asociación cruzada de cohorte retrospectiva de pacientes internados entre enero de 2000 a diciembre de 2018 en un hospital de referencia. Se analizó la relación entre: hacinamiento, colecho, escolaridad materna y paterna, número de hermanos, de convivientes y procedencia, con la falta de adherencia al control médico. Se utilizaron la prueba de chi cuadrado y regresión logística a un nivel de significancia de 0,05. Resultados: Se incluyeron 148 pacientes (103 niños y 45 niñas) entre 2 a 16 años (edad promedio: 8,5± 3,4 años). La falta de adherencia fue encontrada en 73 pacientes (49,3%) que se asoció a procedencia rural (p= 0,012, RR: 1,50, IC95%: 1,10-2,06), baja escolaridad materna (p= 0,046, IC95%: 1,54:1,14-2,08), baja escolaridad paterna (p= 0,02; RR: 1,483, IC95%: 1,09-2,01), >3 convivientes (p=0,007, RR: 1,630, IC95%: 1,21-2,19), colecho (p=0,026; RR: 1,52, IC95%: 1,02-2,27) y hacinamiento (p<0,0001; RR: 1,92, IC95%: 1,39-2,65). Por regresión logística, el hacinamiento (p=0,005; OR= 4,8) y procedencia rural (p=0,022; OR: 2,4) se mantuvieron asociados a la falta de adherencia. Discusión: El hacinamiento y la procedencia rural se asociaron en forma independiente con la pérdida de seguimiento. Se recomienda mayor intervención de la atención primaria de salud.

Introduction: Post-infectious glomerulonephritis (PIGN) in childhood is a risk factor for the development of long-term chronic kidney disease. Adherence to medical control allows secondary nephroprevention to be carried out. Objective: to evaluate the relationship between risk factors related to non-adherence to medical control of patients with IPGN in a pediatric cohort. Methods: descriptive study, with an analytical component of a retrospective cohort of patients hospitalized between January 2000 and December 2018 in a reference hospital. The relationship between: overcrowding, co-sleeping, maternal and paternal education, number of siblings, cohabitants and origin, with lack of adherence to medical control was analyzed. The chi-square test and logistic regression were used at a significance level of 0.05. Results: a total of 148 patients (103 boys y 45 girls) between 2 and 16 years old (mean age: 8.5± 3.4 years) were included. The lack of adherence was found in 73 patients (49.3%) that was associated with rural origin (p= 0.012, RR: 1.50, 95% CI: 1.10-2.06), low maternal education (p= 0.046, 95%CI: 1.54:1.14-2.08), low paternal education (p= 0.02; RR: 1.483, 95%CI: 1.09-2.01), >3 cohabitants (p=0.007, RR: 1.630, 95% CI: 1.21-2.19), co-sleeping (p=0.026; RR: 1.52, 95% CI: 1.02-2.27) and overcrowding (p<0.0001; RR: 1.92, 95% CI: 1.39-2.65). By logistic regression, overcrowding (p=0.005; OR= 4.8) and rural origin (p=0.022; OR: 2.4) remained associated with lack of adherence. Discussion: Overcrowding and rural origin were independently associated with loss to follow-up. Greater intervention by primary health care is recommended.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis / Avaliação dos fatores de risco de aterosclerose e disfunção endotelial em pacientes com glomerulopatias primárias

Abstract Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

Glomeruloesclerosis focal y segmentaria post vacuna COVID-19

La vacuna contra el SARS-CoV-2 ha demostrado eficacia comprobada para el control de la enfermedad, sin embargo, aún se encuentra en estudio los efectos adversos no comunes debido a esta terapia, algunos de tipo renal. Se plantea que una respuesta inmunológica no adecuada podría ser la causa de enfermedades glomerulares asociada a la vacunación. Se reporta el caso de una paciente de 26 años, sin antecedentes de importancia, recibió la inmunidad por la vacuna de SARS-CoV-2 (Sinopharm), posterior a ello inició con proteinuria en rango nefrótico (proteinuria: 24gr en 24 horas), además tuvo albúmina de 2,36 mg/dL y tuvo prueba COVID-19 negativo. Se le realizó biopsia renal con guía ecográfica, con resultado anatomo-patológico de glomeruloesclerosis focal y segmentaria, variante de punta, observándose 17 glomérulos. La paciente fue hospitalizada y recibió inmunosupresión con pulsos de metilprednisolona, prednisona vía oral (1mg/kg/día), atorvastatina (20mg/día), antiagregación plaquetaria con AAS (100mg/día), omeprazol (20mg/día) y profilaxis con trimetoprima-sulfametoxazol. Dos semanas después, la paciente, tuvo una baja de peso (10 kg) y los edemas disminuyeron notoriamente. Cuatro semanas de iniciar el tratamiento, presentó proteinuria < 500 mg/ día, la cual al momento se encuentra en valores normales. Es posible el desarrollo de una glomeruloesclerosis focal y segmentaria de novo, tras la administración de la vacuna contra el SARS-CoV-2, y que respondió al uso de corticoides.

The vaccine against SARS-CoV-2 has demonstrated proven efficacy to control the disease, rare adverse effects due to this therapy are still being studied, some of them renal. It is suggested that an inadequate immune response could be the cause of glomerular diseases associated with vaccination. We describe a 26-year-old patient, with no significant history, received immunity from the SARS-CoV-2 vaccine (Sinopharm), after which he began with proteinuria in the nephrotic range. Proteinuria: 24g in 24 hours. Albumin: 2.36 mg/ dl. COVID-19 test negative. Renal biopsy was performed with ultrasound guidance, with anatomopathological result of Focal and Segmental Glomerulosclerosis, tip variant, observing 17 glomeruli. The patient was hospitalized and received immunosuppression with pulses of methylprednisolone, oral prednisone 1mg/ kg/day, atorvastatin 20mg/day, antiplatelet therapy with ASA 100mg/day, omeprazole 20mg/day, and trimethoprim-sulfamethoxazole prophylaxis. Two weeks later, the patient had a weight loss (10 kg), the edemas decreased significantly. Four weeks after starting treatment, she presented proteinuria <500 mg/day, which at the moment is within normal values. The development of de Novo focal segmental glomerulosclerosis is possible, after administration of the SARS-CoV-2 vaccine, and that responds to the use of corticosteroids.

IgA nephropathy and kidney transplantation according to the Oxford classification / Nefropatia por IgA e transplante renal segundo a classificação de Oxford

Abstract Introduction: IgA nephropathy (IgAN) is the most common glomerular disease globally, and its susceptibility and the risk for the development of end-stage kidney disease are related to genetic and environmental factors. IgAN recurrence after kidney transplantation is relatively common, impacting graft function and survival. This study evaluated the risk factors and the clinical, laboratory, and histological characteristics of post-transplant IgAN recurrence based on the Oxford classification. Material and methods: Retrospective single-center cohort study including kidney transplant recipients with biopsy-proven pre-transplantation IgAN, with analysis of risk factors and clinical, laboratory, and histological characteristics of the IgAN recurrence cases. Results: 53 patients fulfilled the inclusion criteria and were included in the study. The majority was male, white, eutrophic, with a mean age of 27 ± 9 years at IgAN diagnosis. Systemic arterial hypertension and proteinuria were frequent in the pretransplant period. Four recipients (7.5%) presented IgAN recurrence in a period of 6 to 122 months post-transplant. According to the Oxford classification, they had high scores of mesangial hypercellularity and segmental glomerulosclerosis in the native kidney biopsies and there was mesangial hypercellularity in all analyzed graft biopsies. None of these patients had received induction immunosuppression and all of them presented graft failure in the follow-up. Conclusions: In this series, there was a high prevalence of mesangial hypercellularity and segmental glomerulosclerosis on native kidney biopsies, and mesangial hypercellularity occurred in all IgAN recurrence graft biopsies. Despite the lower incidence of recurrence of IgAN post-transplant compared to previous reports, progression to graft loss was of 100%.

Resumo Introdução: Nefropatia por IgA (NIgA) é a doença glomerular mais comum mundialmente. Sua suscetibilidade e risco para desenvolvimento de doença renal em fase terminal estão relacionados a fatores genéticos e ambientais. A recidiva de NIgA pós-transplante é relativamente comum, impactando na função e sobrevida do enxerto. Este estudo avaliou fatores de risco e características clínicas, laboratoriais e histológicas da recidiva de NIgA pós-transplante, com base na classificação de Oxford. Material e métodos: Estudo de coorte retrospectivo de centro único, incluindo receptores de transplante renal com NIgA pré-transplante comprovada por biópsia, com análise dos fatores de risco e características clínicas, laboratoriais e histológicas dos casos de recidiva de NIgA. Resultados: 53 pacientes preencheram critérios de inclusão e foram incluídos no estudo. A maioria era homem, branco, eutrófico, com idade média de 27 ± 9 anos no diagnóstico de NIgA. Hipertensão arterial sistêmica e proteinúria foram frequentes no período pré-transplante. Quatro receptores (7,5%) apresentaram recidiva de NIgA entre 6-122 meses pós-transplante. Segundo a classificação de Oxford, eles apresentaram altos escores de hipercelularidade mesangial e glomeruloesclerose segmentar nas biópsias de rins nativos. Houve hipercelularidade mesangial em todas as biópsias de enxerto analisadas. Nenhum destes pacientes recebeu imunossupressão de indução. Todos apresentaram falência do enxerto no acompanhamento. Conclusões: Nesta série, houve alta prevalência de hipercelularidade mesangial e glomeruloesclerose segmentar em biópsias de rins nativos, e hipercelularidade mesangial ocorreu em todas as biópsias do enxerto de recidiva da NIgA. Apesar da menor incidência de recidiva de NIgA pós-transplante comparada a relatos anteriores, a progressão para perda do enxerto foi de 100%.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

Glomerulonefritis aguda posinfecciosa como riesgo para desarrollar insuficiencia renal crónica en una cohorte pediátrica de un hospital de referencia en Paraguay

Contexto: la glomerulonefritis aguda posinfecciosa (GNPI) representa un riesgo para el desarrollo de insuficiencia renal a largo plazo. Objetivo: describir la incidencia de proteinuria persistente y factores asociados en pacientes con antecedente de GNPI en una cohorte pediátrica de un hospital de referencia en Paraguay. Metodología: se incluyó a 121 pacientes con síndrome nefrítico con C3 disminuido, con normalización a los tres meses, aunque no se haya comprobado etiología estreptocócica. Se excluyó a los pacientes con enfermedad renal previa, con síndrome nefrítico secundario y con menos de seis meses de seguimiento. Se analizaron las características sociodemográficas, infecciones precedentes, aclaramiento de creatinina, días de hipertensión arterial y de internación, además de la relación de estas con la persistencia de proteinuria a los seis meses y más de seguimiento. Resultados: de los 121 pacientes entre 2 a 16 años de edad incluidos, 75 pacientes tuvieron un seguimiento médico entre 6 y 48 meses, de los cuales 43 (57,3 %) desarrollaron proteinuria persistente, la cual se asoció con un menor aclaramiento de creatinina (p = 0,03; 67,74 ± 25,69 mL/min/1,73 m2 SC vs. 80,22 ± 2,98 mL/min/1,73 m2 SC), con el número promedio de convivientes (6,3 ± 2,8 vs. 5,3 ± 2,3; p = 0,027) y el número promedio de hijos (4,3 ± 2,7 vs. 3,6 ± 2,3; p = 0,048). No se encontró asociación con las otras características. Conclusiones: la incidencia de proteinuria se asoció con un menor aclaramiento de creatinina y con una mayor frecuencia de los determinantes sociales en salud.

Background: Acute post-infectious glomerulonephritis (PIGN) represents a risk for the development of long-term renal failure. Purpose: To describe the incidence of proteinuria in patients with a history of PIGN in a pediatric cohort at a referral hospital in Paraguay. Methodology: a total of 121 patients with nephritic syndrome with decreased C3 and normalization at 3 months, although streptococcal aetiology has not been proven were included. Patients with with previous kidney disease, with secondary nephritic syndrome and with less than 6 months of follow up were excluded. Sociodemographic characteristics, previous infection, creatinine clearance, days of arterial hypertension and hospitalization were analyzed, in addition to their relationship with the persistence of proteinuria at 6 months and more of follow-up. Results: Of the 121 patients between 2 and 16 years of age included, 75 patients had a medical follow-up between 6 and 48 months, 43 (57.3 %) of them developed persistent proteinuria, which was associated with lower creatinine clearance (p = 0.03; 67.74 ± 25.69 mL/min/1.73 m2 BM vs 80.22 ± 2.98 mL/min/1.73 m2 BM), higher average number of cohabitants (6.3 ±2.8 vs 5.3±2.3; p= 0.027) and higher average number of children (4.3±2.7 vs 3.6±2.3; p= 0.048). No association was found with other characteristics. Conclusions: the incidence of proteinuria in this series was associated with lower creatinine clearance and a higher frequency of social determinants in health.

¿Cuándo realizar biopsia renal en un paciente diabético?. A propósito de un caso en una ciudad de altura

Se reporta el caso de un paciente varón de 54 años, habitante de una ciudad de altura, con antecedentes de diabetes mellitus tipo 2 e hipertensión arterial en tratamiento, con microhematuria persistente, elevación de creatinina, presencia de proteinuria y ausencia de retinopatía diabética, a quien se le realizó biopsia renal por sospecha de glomerulopatía no diabética asociada. La biopsia renal confirmó el diagnóstico histopatológico de glomeruloesclerosis nodular diabética. Debido a que usualmente no se realiza biopsia renal en pacientes diabéticos, se presenta este caso y se revisa sus indicaciones. Asimismo, planteamos que la altura pudo influir en el deterioro de la función renal.

We report the case of a 54-year-old male patient, high altitude city dweller, with a history of type 2 diabetes mellitus and arterial hypertension in treatment, with persistent microscopic hematuria, creatinine elevation, presence of proteinuria and absence of diabetic retinopathy, who underwent renal biopsy for suspected associated non-diabetic glomerulopathy. Kidney biopsy confirmed the histopathological diagnosis of diabetic nodular glomerulosclerosis Because renal biopsy is usually not performed in diabetic patients, this case is presented and its indications are reviewed. Also, we propose that high altitude could influence in the renal function impairment.

Membranoproliferative glomerulonephritis: current histopathological classification, clinical profile, and kidney outcomes / Glomerulonefrite membranoproliferativa: classificação histopatológica atual, perfil clínico e desfechos renais

Abstract Introduction: Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease with a variable prognosis. A new classification based on the presence or absence of immunoglobulins and complement deposits in immunofluorescence microscopy (IF) of kidney biopsy has recently been proposed. The objectives of the study were to determine and compare the clinical, laboratory, and histopathological characteristics of those with primary or secondary MPGN, reclassify the primary ones based on IF findings, and evaluate kidney outcomes. Methods: This was an observational retrospective cohort study carried out in a single center (UNIFESP), based on the data collected from medical records of patients followed from 1996 to 2019. Results: Of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. Most patients were hypertensive (84.9%) and had edema (88.7%) and anemia (84.9%); 33 (91.7%) patients classified as primary MPGN were reclassified as immune-complex-mediated and 3 (8.3%) as complement-mediated. The secondary MPGN group had hematuria more frequently (p <0.001) and a higher prevalence of deposits of IgG (p = 0.02) and C1q (p = 0.003). Regarding the outcome, 39% of the patients achieved partial or complete remission. Lower initial serum albumin and higher initial 24-hour proteinuria were factors associated with worst renal prognosis. Conclusions: According to the new histological classification, the vast majority of MPGN cases were classified as being mediated by immune complexes. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics.

Resumo Introdução: Glomerulonefrite membranoproliferativa (GNMP) é uma doença glomerular rara com prognóstico variável. Recentemente, foi proposta uma nova classificação baseada na presença ou ausência de imunoglobulinas e depósitos de complemento na microscopia de imunofluorescência (IF) da biópsia renal. Os objetivos do estudo foram determinar e comparar as características clínicas, laboratoriais e histopatológicas daqueles com GNMP primária ou secundária, reclassificar as primárias com base em achados da IF e avaliar os desfechos renais. Métodos: Este foi um estudo de coorte observacional retrospectivo realizado em centro único (UNIFESP), com base nos dados coletados de prontuários de pacientes acompanhados de 1996 a 2019. Resultados: Dos 53 casos de GNMP, 36 (67,9%) foram classificados como GNMP primária e 17 (32,1%) como GNMP secundária. A maioria dos pacientes era hipertensa (84,9%) e apresentava edema (88,7%) e anemia (84,9%); 33 (91,7%) pacientes classificados como GNMP primária foram reclassificados como mediados por imunocomplexo e 3 (8,3%) como mediados por complemento. O grupo de GNMP secundária apresentou mais frequentemente hematúria (p <0,001) e maior prevalência de depósitos de IgG (p = 0,02) e C1q (p = 0,003). Com relação ao desfecho, 39% dos pacientes alcançaram remissão parcial ou completa. Albumina sérica inicial mais baixa e proteinúria de 24 horas inicial mais elevada foram fatores associados a pior prognóstico renal. Conclusões: De acordo com a nova classificação histológica, a grande maioria dos casos de GNMP foram classificados como sendo mediados por imunocomplexos. Houve poucas diferenças entre GNMP primária e secundária em relação às suas características clínicas e laboratoriais.

Kidney Disease in Ankylosing Spondylitis: a case series and review of the literature / Doença Renal na Espondilite Anquilosante: uma série de casos e revisão da literatura

Abstract Background Kidney disease is a rare manifestation of ankylosing spondylitis (AS) and its pathological alterations remain poorly described. The aim of this study was to investigate the clinical presentation and pathological alterations on kidney biopsy of AS patients and review and discuss the current literature on the issue. Methods: We retrospectively studied the clinical presentation and kidney pathological alterations of 15 Caucasian AS patients submitted to kidney biopsy between October 1985 and March 2021. Results: Patients were predominantly male (66.7%) with median age at the time of kideney biopsy of 47 years [IQR 34 - 62]. Median serum creatinine at presentation was 1.3 mg/dL [IQR 0.9 - 3] and most patients also had either proteinuria (85.7%) and/or hematuria (42.8%). The most common indication for kidney biopsy was nephrotic syndrome (33.3%), followed by acute or rapidly progressive kidney injury (20%) and chronic kidney disease of unknown etiology (20%). Chronic interstitial nephritis (CIN) (n=3) and AA amyloidosis (n=3) were the most common diagnosis. Others included IgA nephropathy (IgAN) (n=2), focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=1), and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)(n=1). Conclusions: We present one of the largest series of biopsy-proven kidney disease in Caucasian AS patients. We found a lower prevalence of IgAN than previously reported in Asian cohorts. We found a higher prevalence of CIN and a lower prevalence of AA amyloidosis than that described in previous series of Caucasian patients. We also present the first case of AS-associated IC-MPGN.

Resumo Antecedentes: A doença renal é uma manifestação rara de espondilite anquilosante (EA) e as suas alterações patológicas permanecem pouco descritas. O objetivo deste estudo foi investigar a apresentação clínica e alterações patológicas na biópsia renal de doentes com EA bem como rever e discutir a literatura atual sobre o assunto. Métodos: Estudamos retrospectivamente a apresentação clínica e alterações patológicas renais de 15 doentes caucasianos com EA submetidos a biópsia renal entre Outubro de 1985 e Março de 2021. Resultados: Os doentes eram predominantemente homens (66,7%) com idade mediana no momento da biópsia de 47 anos [IIQ 34 - 62]. A creatinina sérica mediana na apresentação foi de 1,3 mg/dL [IIQ 0,9 - 3] e a maioria dos pacientes apresentava também proteinúria (85,7%) e/ou hematúria (42,8%). A indicação mais comum para biópsia renal foi a síndrome nefrótica (33,3%), seguida de lesão renal aguda ou rapidamente progressiva (20%) e doença renal crónica de etiologia desconhecida (20%). A Nefrite intersticial crónica (NIC) (n=3) e a amiloidose AA (n=3) foram os diagnósticos mais comuns. Outros incluíram nefropatia por IgA (NIgA) (n=2), glomeruloesclerose segmentar focal (n=2), nefropatia membranosa (n=1) e glomerulonefrite membranoproliferativa mediada por imunocomplexos (GNMP-IC) (n=1). Conclusões: Apresentamos uma das maiores séries de doenças renais comprovadas por biópsia em doentes caucasianos com EA. Encontramos uma prevalência de NIgA menor do que a relatada anteriormente em coortes asiáticas. Encontramos uma maior prevalência de NIC e uma prevalência menor de amiloidose AA do que a descrita em séries anteriores de pacientes caucasianos. Também apresentamos o primeiro caso de GNMP-IC associada à EA.

Caracterización de enfermedades glomerulares: análisis de 22 años de biopsias renales / Frequency of glomerular diseases in an analysis of 550 kidney biopsies

BACKGROUND: The frequency of glomerular diseases is dynamic and varies according to geographic area. AIM: To evaluate the frequency of primary and secondary glomerulopathies, their demographic profile and main clinical characteristics. MATERIAL AND METHODS: Renal biopsies from native kidneys performed between 1999 and 2020 were retrospectively reviewed. Demographic characteristics, clinical presentation, most relevant laboratory tests, frequency of primary and secondary glomerulopathies were analyzed. RESULTS: We analyzed 550 kidney biopsies from patients with a median age of 48 years (64% females). Nephrotic syndrome was the main indication for renal biopsy. Primary and secondary glomerulopathies occurred with similar frequency. Within the primary glomerulopathies, membranous nephropathy (34.1%) was the most common, followed by IgA nephropathy (31.1%) and focal segmental glomerulosclerosis (14.1%). Among the secondary glomerulopathies, lupus nephropathy was the most common (41.7%), followed by pauciimmune glomerulonephritis (27.1%) and diabetic nephropathy (6.4%). When comparing the results with other regions, significant differences were observed with reported frequencies in United States, Europe, Asia and the rest of Latin America. CONCLUSIONS: The most common primary glomerulopathies were membranous nephropathy and IgA nephropathy. Among the secondary glomerulopathies lupus nephropathy and pauci-immune glomerulonephritis were the most common. Compared to international registries, we observed a high proportion of membranous nephropathy and pauci-immune glomerulonephritis.

The application of antineutrophil cytoplasmic antibody renal risk score in children with antineutrophil cytoplasmic antibody-associated glomerulonephritis / 中华实用儿科临床杂志

Objective:To investigate the potential of the antineutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) in predicting the prognosis of children with ANCA-associated glomerulonephritis (AAGN).Methods:Laboratory testing, renal pathology results, treatment and prognosis of 61 children with AAGN diagnosed by renal biopsy from June 2007 to May 2022 in General Hospital of Eastern Theater Command were retrospectively analyzed.The Kaplan-Meier method was used to evaluate the overall and renal survival of children with AAGN, and risk factors of progression to end stage renal disease (ESRD) were analyzed by Cox regression analysis. Results:Among the 61 children with AAGN, there were 14 males and 47 females with the age of (15.65±3.74) years.According to ARRS, AAGN children were assigned into low-risk group (27 cases), medium-risk group (21 cases) and high-risk group (13 cases). During a median follow-up duration of 46.36 (14.58, 95.62) months, the number of ESRD cases in the high-risk group (9 cases) was significantly higher than that of low-risk group (2 cases) and medium-risk group (3 cases) ( χ2=13.079, P<0.001). Kaplan-Meier survival analysis showed that AAGN children in the high-risk group had the worst renal prognosis ( χ2=5.796, P=0.016), while no significant difference was detected in the overall survival among the 3 groups ( χ2=2.883, P=0.237). Multivariate Cox regression showed that estimate glomerular filtration rate(eGFR)≤15 mL/(min·1.73 m 2) ( HR=9.574, 95% CI: 4.205-25.187, P=0.015) and ARRS ( HR=2.115, 95% CI: 1.206-4.174, P=0.012) were independent risk factors for children with AAGN progress to ESRD.Receiver operating characteristic (ROC) curve analysis results showed that the area under the curve of ARRS for predicting the risk of progressing to ESRD in AAGN children was 0.880 (95% CI: 0.759-1.000), and the optimal cutoff value of ARRS was 5.50, with the sensitivity and specificity of 85.71% and 82.98%, respectively. Conclusions:ARRS was an independent risk factor for children with AAGN progress to ESRD, which had a predictive value for the progression of AAGN to ESRD.

Changes of gut microflora in newly diagnosed IgA nephropathy patients and its correlation with clinical risk factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the gut microbiota in newly diagnosed IgA nephropathy patients with chronic kidney disease (CKD) stages 1-2 and the association between the gut microbiota and the clinical risk factors of IgA nephropathy.@*METHODS@#Fresh fecal samples were collected from nineteen newly diagnosed IgA nephropathy patients with CKD stages 1-2 and fifteen age- and sex-matched healthy controls. Fecal bacterial DNA was extracted and microbiota composition were characterized using 16S ribosomal RNA (16S rRNA) high-throughput sequencing for the V3-V4 region. The Illumina Miseq platform was used to analyze the results of 16S rRNA high-throughput sequencing of fecal flora. At the same time, the clinical risk factors of IgA nephropathy patients were collected to investigate the association between the gut microbiota and the clinical risk factors.@*RESULTS@#(1) At the phylum level, the abundance of Bacteroidetes was significantly reduced (P=0.046), and the abundance of Actinobacteria was significantly increased (P=0.001). At the genus level, the abundance of Escherichia-Shigella, Bifidobacte-rium, Dorea and others were significantly increased (P < 0.05). The abundance of Lachnospira, Coprococcus_2 and Sutterella was significantly reduced (P < 0.05). (2) There was no significant difference in the abundance of gut microbiota between the newly diagnosed IgA nephropathy patients and the healthy control group (P>0.05), but there were differences in the structure of the gut microbiota between the two groups. The results of LEfSe analysis showed that there were 16 differential bacteria in the newly diagnosed IgA nephropathy patients and healthy controls. Among them, the abundance of the newly diagnosed IgA nephropathy patients was increased in Enterobacteriales, Actinobacteria, Escherichia-Shigella, etc. The healthy control group was increased in Bacteroidetes and Lachnospira. (3) The result of redundancy analysis (RDA) showed that Bifidobacterium was positively correlated with serum IgA levels, 24-hour urinary protein levels and the presence of hypertension. Lachnoclostridium was positively correlated with the presence of hypertension. Escherichia-Shigella was positively correlated with urine red blood cells account. Bifidobacterium was positively correlated with the proliferation of capillaries. Faecalibacterium was positively correlated with cell/fibrocytic crescents. Ruminococcus_2 was positively correlated with mesangial cell proliferation, glomerular segmental sclerosis and renal tubular atrophy/interstitial fibrosis.@*CONCLUSION@#The gut microbiota in the newly diagnosed IgA nephropathy patients with CKD stages 1-2 is different from that of the healthy controls. Most importantly, some gut bacteria are related to the clinical risk factors of IgA nephropathy. Further research is needed to understand the potential role of these bacteria in IgA nephropathy.

Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Síndrome de Frasier: ¿Cómo diagnosticar una enfermedad rara en la consulta de Ginecología? Reporte de caso / Frasier Syndrome: How to diagnose a rare disease in a Gynecology consultation? A case report

Resumen INTRODUCCIÓN: El síndrome de Frasier es una enfermedad de herencia autosómica dominante con una prevalencia inferior a 1 caso por cada millón de recién nacidos vivos. Hasta la fecha se han descrito unos 150 casos. Este síndrome se caracteriza por pseudohermafroditismo masculino, disgenesia gonadal 46, XY y enfermedad glomerular, todo ello producido por una mutación del gen WT1. CASO CLÍNICO: Paciente de 16 años que consultó por amenorrea primaria y ausencia de caracteres sexuales secundarios. Antecedentes: glomerulonefritis focal segmentaria corticorresistente desde la infancia. En la exploración física se objetivó un estadio Tanner 1. Las pruebas complementarias pusieron de manifiesto la ausencia de útero y anejos y un hipogonadismo hipergonadotrópico con cariotipo 46, XY. Ante los hallazgos se decidió la laparoscopia exploradora y salpingooforectomía bilateral. El informe anatomopatológico fue de disgerminoma de ovario derecho. La sospecha clínica se confirmó en el estudio genético, que reportó una mutación del gen WT1, diagnóstica de síndrome de Frasier. En la actualidad, la paciente recibe tratamiento inmunosupresor y hormonal sustitutivo, con una evolución favorable. CONCLUSIÓN: El diagnóstico temprano del síndrome de Frasier es fundamental en virtud del riesgo asociado de malignidad. La baja frecuencia de la enfermedad y la asociación común con retraso puberal en pacientes con enfermedades crónicas puede favorecer el retraso del diagnóstico. El reporte de los casos diagnosticados de este síndrome, y el tratamiento multidisciplinario son decisivos para mejorar el conocimiento de esta rara enfermedad.

Abstract INTRODUCTION: Frasier Syndrome is an autosomal dominant inherited disease with a prevalence of less than 1 per million live births. To date, about 150 cases have been described. This syndrome is characterized by male pseudohermaphroditism, 46, XY gonadal dysgenesis, and glomerular disease, all caused by a mutation of the WT1 gene. It is essential to learn more about this disease, not only because of the high risk of ovarian neoplasia, but also because its early diagnosis will improve the prognosis. CLINICAL CASES: We report the case of a 16-year-old woman who consulted for primary amenorrhea and absence of secondary sexual characteristics. As medical history, she highlighted steroid-resistant focal segmental glomerulonephritis since childhood. The examination revealed Tanner stage 1. Complementary tests revealed the absence of the uterus and adnexa and hypergonadotropic hypogonadism with a 46, XY karyotype. Given the findings, it was decided to perform an exploratory laparoscopy and bilateral salpingo-oophorectomy. The anatomopathological result reported dysgerminoma of the right ovary. The clinical suspicion was confirmed by genetic study, which reported a mutation of the WT1 gene, diagnostic of Frasier Syndrome. Currently, the patient undergoes, along with immunosuppressive treatment, hormone replacement therapy, with a favorable evolution. CONCLUSION: Early diagnosis of Frasier Syndrome is essential given the associated risk of malignancy. The low frequency of the disease and the usual association of delayed puberty in patients with chronic diseases may lead to a diagnostic delay. Therefore, reporting the diagnosed cases of this syndrome, as well as its multidisciplinary management, is essential to improve knowledge about this rare disease.

Severe bilateral visual loss as the first sign of IgA nephropathy / Perda visual bilateral grave como o primeiro sinal da nefropatia por IgA

ABSTRACT We describe a case of a 33-years-old woman who presents with severe acute bilateral visual loss secondary to massive exudative hypertensive maculopathy as the first sign of immunoglobulin A nephropathy. The patient's ophthalmic examination showed bilateral cotton-wool spots, flame-shaped retinal hemorrhages, diffuse narrow arterioles, optic disk edema, and exudative maculopathy. Systemic workup demonstrated a systolic and diastolic blood pressure of 240 mmHg and 160 mmHg, respectively, proteinuria, and hematuria, suggesting kidney disease as the causative condition. A kidney biopsy confirmed immunoglobulin A nephropathy. She was treated with systemic corticosteroids, antihypertensive drugs, and a single bilateral intravitreal injection of aflibercept. There was a prompt resolution of macular edema and vision improvement. Our case draws attention to the fact that severe bilateral visual loss can be the first sign of severe hypertension. Secondary causes, such as immunoglobulin A nephropathy, should be ruled out.

RESUMO Nosso objetivo é descrever uma paciente de 33 anos de idade, com perda visual bilateral grave por maculopatia hipertensiva exsudativa como o primeiro sinal da nefropatia por imunoglobulina A. A fundoscopia revelou a presença de manchas algodonosas, hemorragias em chama-de-vela, estreitamento arteriolar difuso, edema de disco óptico e maculopatia exsudativa bilateral. A pressão arterial sistólica foi de 240mmHg e a diastólica de 160 mmHg associado a proteinúria e hematúria, sugerindo a presença de doença renal. A biópsia renal confirmou a nefropatia por imunoglobulina A. A paciente foi tratada como corticoide sistêmico, drogas anti-hipertensivas e uma única dose intravítrea de Aflibercept em ambos os olhos. Houve rápida melhora do edema macular e da acuidade visual. Nosso caso chama a atenção para o fato de que a perda visual bilateral grave pode ser a primeira apresentação de uma doença hipertensiva sistêmica. Causas secundárias como a nefropatia por imunoglobulina A devem ser afastadas.

Complicaciones de glomerulonefritis aguda postestreptocócica en el servicio de nefrología del Hospital Infantil Doctor Robert Reid Cabral / Complications of acute poststreptococcal glomerulonephritis in the nephrology department of the Children's Hospital Dr. Robert Reid Cabral

Conflicto de intereses Inexistencia de conflicto de intereses Aspectos éticos El presente estudio fue ejecutado con apego a las normativas éticas internacionales, incluyendo los aspectos relevantes de la Declaración de Helsinki y del Consejo de Organizaciones Internacionales de las Ciencias Médicas (CIOMS) donde se observa que el propósito principal de la investigación médica en seres humanos es mejorar los procedimientos preventivos, diagnósticos y terapéuticos, y también comprender la etiología y patogenia de las enfermedades. Incluso, los mejores métodos preventivos, diagnósticos y terapéuticos disponibles deben ponerse a prueba continuamente a través de la investigación para que sean eficaces, efectivos, accesibles y de calidad.1 Tomando estas pautas el protocolo del presente estudio y los instrumentos diseñados para el mismo fueron sometidos a la revisión del Comité de Ética de la Universidad Nacional Pedro Henríquez Ureña, a través de la Escuela de Medicina y de la coordinación de la Unidad de Investigación de la Universidad, así como al comité de investigación del hospital infantil Dr. Robert Reid Cabral, cuya aprobación fue el requisito para el inicio del proceso de recopilación y verificación de datos. Por lo tanto, el estudio implicó el manejo de datos identificatorios, ofrecidos por el personal que labora en el centro de salud. Los mismos fueron analizados con suma cautela e introducidos en la base de datos creada de forma que toda información fuese protegida por una clave asignada únicamente por los investigadores para de esta manera mantener el estricto apego a la confidencialidad. Introducción. La glomerulonefritis aguda posestreptocócica (GNAPE), es una enfermedad frecuente en pediatría. Se presenta posterior a una infección causada por estreptococo betahemolítico del grupo A. Se caracteriza por la tríada de edema, hematuria e hipertensión. Objetivo: Determinar la frecuencia de complicaciones de glomerulonefritis aguda posestreptocócica en el hospital infantil Dr. Robert Reid Cabral, 2020-2021. Material y métodos: Para la obtención de los datos fue diseñado un formulario que contiene un total de 8 acápites donde se describen datos sociodemográficos como la edad, sexo, estación del año y datos relacionados con las complicaciones, antecedentes patológicos, comorbilidades, manifestaciones clínicas y función renal. Resultados: De los 426 expedientes clínicos de pacientes pediátricos, en estos se encontró que 19,2 por ciento presentaron complicaciones de glomerulonefritis aguda posestreptocócica. Conclusión: En la investigación, se pudo determinar que la crisis hipertensiva fue la complicación más frecuente con un 50,0 por ciento. El 46,3 por ciento de los pacientes tenían edad entre 10 y 14 años. El 57,3 por ciento eran masculino. El 28,0 por ciento de los casos tuvieron mayor prevalencia en otoño. La infección cutánea fue el antecedente patológico más frecuente con un 65,8 por ciento. El asma fue la comorbilidad más frecuente con un 42,3 por ciento. La hipertensión arterial fue la manifestación clínica más frecuente con un 93,9 por ciento. El 39,0 por ciento de los pacientes presentaron una función renal grado II.

Introduction. Acute poststreptococcal glomerulo-nephritis (PSGN) is a common disease in pediatrics. It presents after an infection caused by group A beta-he-molytic streptococcus. It is characterized by the triad of edema, hematuria, and hypertension.Objective: To determine the frequency of complica-tions of acute poststreptococcal glomerulonephritis at the hospital infantil Dr. Robert Reid Cabral, 2020-2021.Material and method. To obtain the data, a form was designed that contains a total of 8 sections where socio-demographic data such as age, sex, season of the year and data related to complications, pathological history, comorbidities, clinical manifestations and renal func-tion are described.Results. Of the 426 clinical records of pediatric pa-tients, it was found that 19.2 percent presented compli-cations of acute poststreptococcal glomerulonephritis.Conclusion. In the investigation, it was possible to de-termine that the hypertensive crisis was the most fre-quent complication with 50.0 percent. 46.3 percent of the patients are between 10 and 14 years old. 57.3 percent were male. 28.0 percent of the cases had hi-gher prevalence in autumn. Cutaneous infection was the most frequent pathological antecedent with 65.8 percent. Asthma was the most frequent comorbidity with 42.3 percent. Arterial hypertension was the most frequent clinical manifestation with 93.9 percent. 39.0 percent of the patients presented renal function grade II

Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?

SUMMARY OBJECTIVE: Sclerostin is a protein produced by osteocytes, kidneys, and vascular cells and has many effects on kidney and vascular structures. Soluble TNF-related weak inducer of apoptosis is a proinflammatory cytokine that may cause glomerular and tubular injury and increase sclerostin expression. This study aimed to investigate serum sclerostin and soluble TNF-related weak inducer of apoptosis levels in patients with glomerulonephritis and the effects they may be associated with. METHODS: This cross-sectional study included 93 patients, 63 of whom were glomerulonephritis and 30 were healthy controls. Serum sclerostin, soluble TNF-related weak inducer of apoptosis, and 24-h urinary protein excretion were measured, and pulse wave velocity was calculated for arterial stiffness. RESULTS: Serum sclerostin and soluble TNF-related weak inducer of apoptosis were higher in glomerulonephritis patients than in the control group, and serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were correlated with both proteinuria and pulse wave velocity. In addition, in the regression analysis, serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were found to be independent predictors of proteinuria in patients with glomerulonephritis. CONCLUSION: This is the first study to show that serum sclerostin and soluble TNF-related weak inducer of apoptosis are elevated in glomerulonephritis patients, and these two markers correlate with arterial stiffness and proteinuria in these patients. Considering the effects of sclerostin and soluble TNF-related weak inducer of apoptosis in patients with glomerulonephritis, we think these mechanisms will be the target of both diagnosis and new therapies.

Mechanism of Alisma plantago-aquatica Linn. improving chronic glomerulonephritis based on network pharmacology and experimental verification / 药学学报

This study aims to explore the improvement and the mechanism of the Alisma plantago-aquatica Linn. (ApL) on chronic glomerulonephritis (CGN). All animal experiments were followed the regulation of the Experimental Animal Ethical Committee of Shanghai University of Traditional Chinese Medicine. CGN mouse model was established by a single tail-vein injection of doxorubicin (Dox) (20 mg·kg-1). One week after Dox administration, the mice received water extract of ApL (85 and 255 mg·kg-1) by gavage once a day for 14 days. At the end of experiment, the urine albumin-to-creatinine ratio (ACR), serum albumin (ALB), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected, kidney histopathological H&E staining was analyzed. Active ingredients and action targets of ApL were collected from TCMSP database, and CGN-related targets were obtained from Genecards database. STRING platform was employed to perform protein-protein interaction (PPI), and Metascape platform was used for KEGG pathway and GO enrichment analysis. The results of experiments demonstrated that ApL (85 and 255 mg·kg-1) could reduce the ACR and the content of SCr and BUN, and increase the content of ALB in mice. Network pharmacology results predicted that nuclear factor kappa-B (NF-κB)-related pathway and biological process of oxidoreductase activity regulation may be involved in the ApL-provided amelioration on CGN. The verification results showed that ApL could inhibit the activation of NF-κB and the expression of inflammatory factors in mice, and reduce the activity of renal myeloperoxidase (MPO). Meanwhile, ApL promoted the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream gene mRNA, and reduced the level of renal malondialdehyde (MDA) and reactive oxygen species (ROS), and further elevated renal glutathione (GSH) level. Based on network pharmacology combined experiments, this study found that ApL may improve CGN in mice through multiple targets and multiple pathways, in which the inhibition of NF-κB signaling and the activation of Nrf2 signaling may be important mechanisms involved.

Alkaptonuria with IgA nephropathy: a case report and literature review / 中华肾脏病杂志

The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.

Comparison of efficacy and safety of rituximab at different doses in the treatment of idiopathic membranous nephropathy / 中华肾脏病杂志

It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m 2 experimental treatment group (375 mg/m 2 once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m 2 experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m 2 experimental treatment group (87.1% vs. 65.8%, χ2=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m 2 experimental treatment group ( χ2=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m 2 experimental treatment group ( χ2=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m 2 experimental treatment group ( χ2=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m 2 experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ2=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m 2 experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m 2 experimental treatment group than that in the 1 g standard treatment group ( Fisher value=8.593, P=0.015). Both 375 mg/m 2 regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m 2 regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.