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.

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3 / 中南大学学报(医学版)

Objective:With the in-depth study of complement dysregulation,glomerulonephritis with dominant C3 has received increasing attention,with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types.This study analyzes the clinical,pathological,and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3,aiming to avoid misdiagnosis and missed diagnoses. Methods:The clinical,pathological,and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed.According to the clinical feature and results of pathology,15 patients with post-infectious glomerulonephritis(PIGN)and 37 patients with of non-infectious glomerulonephritis(N-PIGN)were classified.N-PIGN subgroup analysis was performed,and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group,or 27 in a C3 glomerulopathy(C3G)group and 10 in a non-C3 nephropathy(N-C3G)group. Results:The PIGN group had lower creatinine values(84.60 μmol/L vs 179.62 μmol/L,P= 0.001),lower complement C3 values(0.36 g/L vs 0.74 g/L,P<0.001)at biopsy,and less severe pathological chronic lesions compared with the N-PIGN group.In the N-PIGN subgroup analysis,the C3-dominant-deposition group had higher creatinine values(235.30 μmol/L vs 106.70 μmol/L,P=0.004)and higher 24-hour urine protein values(4 025.62 mg vs 1 981.11 mg,P=0.037)than the C3-alone-deposition group.The prognosis of kidney in the PIGN group(P=0.049),the C3-alone-deposition group(P=0.017),and the C3G group(P=0.018)was better than that in the N-PIGN group,the C3-dominant-deposition group,and the N-C3G group,respectively. Conclusion:Glomerulonephritis with dominant C3 covers a variety of pathological types,and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G;in addition,the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis,and relevant diagnosis,treatment,and follow-up should be strengthened.

Analysis on clinicopathology and prognosis of primary IgA nephropathy in children with massive proteinuria / 中华肾脏病杂志

Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

Chronic active EB virus infection in a child with the onset of IgA nephropathy / 中华肾脏病杂志

Chronic active Epstein-Barr virus (CAEBV) infection with renal involvement is not common. The paper reported a child of multisystem-compromised CAEBV infection with the onset of IgA nephropathy (IgAN). The child presented with intermittent gross hematuria, and renal biopsy showed focal proliferative IgAN, administered methylprednisolone pulse followed by oral prednisolone treatment. Intermittent increase of blood Epstein-Barr virus (EBV) load and abnormal EBV antibody, pneumonia caused by EBV and Staphylococcus aureus-mixed infection, periappendiceal abscess, and pancytopenia occurred during treatment follow-up. The CAEBV infection was considered. Echocardiography suggested pulmonary hypertension. Head CT presented multiple calcifications in the bilateral basal ganglia. Bone marrow biopsy showed bone marrow EBV-DNA 6.5×10 3 copies per liter. Immunohistochemistry of renal biopsy showed about 50 CD8 + (scattered +) cells per high power field (HPF), about 40 CD4 + (focal +) cells per HPF (local), CD68 + (-), latent membrane protein 1 (-), EBV-encoded small RNA (scattered +) approximately 25 cells per HPF. The lymphocyte subsets infected with EBV showed CD4 + T cells EBV-DNA 3.4×10 4 copies per 1 million cells, CD8 + T cells EBV-DNA 3.3×10 5 copies per 1 million cells, B cells EBV-DNA 1.25×10 4 copies per 1 million cells, NK cells/NK T cells EBV-DNA 2.3×10 4 copies per 1 million cells. The clinical diagnosis was CAEBV infection and EBV-associated IgAN. The patient currently receives oral prednisone treatment, and it is recommended to undergo hematopoietic stem cell transplantation and treatment is under follow up.

Researches progress on pathogenesis of IgA nephropathy / 中华肾脏病杂志

IgA nephropathy (IgAN) is currently the most common primary glomerulonephritis worldwide, with 20%-40% of patients progressing to end-stage renal disease within 20 years of diagnosis. At present, the pathogenesis of IgAN is not clear, and clinical treatment is mainly to control the progression, without specific treatment plan. A series of studies on galactose-deficient IgA1 (Gd-IgA1) suggest that the pathogenesis of IgAN involves multiple links. This review summarizes the research progress on the pathogenesis of IgAN, covering the structure characteristics of IgA1, Gd-IgA1 antibodies and Gd-IgA1 immune complexes in IgAN patients, the deposition of Gd-IgA1 immune complexes in the kidneys, kidney damage following the deposition of Gd-IgA1 immune complexes, the role of complement in IgAN, the genomics of IgAN, and mucosal immunity in IgAN, providing clues and insights for further research and clinical treatment.

New progress in the treatment of immunoglobulin A nephropathy / 中国医师杂志

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by the deposition of IgA in the mesangial area of the glomerulus. At present, the pathogenesis of IgAN is not yet clear, and there has been a lack of specific and recognized treatment plans. In recent years, many domestic and foreign researchers have conducted research on important pathways and key molecules in its pathogenesis, aiming to explore new therapeutic drugs. This review mainly summarizes the latest progress in the treatment of IgAN, including drugs that have been proven effective against IgAN and drugs that are currently being evaluated in clinical studies.

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.

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.

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.

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.

Research advances in hepatitis B virus-associated glomerulonephritis / 临床肝胆病杂志

There is are large number of patients with chronic hepatitis B virus (HBV) infection. HBV not only damages the liver, but also involves the kidney. Hepatitis B virus-associated glomerulonephritis (HBV-GN) is secondary glomerulonephritis caused by HBV infection, and it is one of the most common extrahepatic complications of HBV infection. HBV-GN is mainly observed in children and young and middle-aged adults, with varying degrees of proteinuria as the main clinical manifestation, and it may be accompanied by hematuria and hypertension. Membranous nephropathy is the most common pathological type, followed by membrano-proliferative glomerulonephritis and IgA nephropathy. HBV-GN has an insidious onset and lacks characteristic symptoms and pathological manifestations, and thus it may be easily confused with various types of glomerulonephritis, which may lead to missed diagnosis and misdiagnosis. HBV-GN has a complex pathogenesis involving various links such as immune disorders, direct viral damage, and genetics, among which the theory of immune complex deposition has been widely recognized. In recent years, some important advances have been made in the research on the pathogenesis, diagnosis, and treatment of HBV-GN. This article summarizes the above issues, so as to provide a reference for clinical diagnosis and treatment.

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.