Clinical analysis of acute post-streptococcal glomerulonephritis and C 3 glomerulopathy in children / 中华实用儿科临床杂志

Objective:To investigate the clinical features of acute post-streptococcal glomerulonephritis (APSGN) and C 3 glomerulopathy (C 3G) in children, and to improve the understanding, diagnosis and treatment of C 3G in children with atypical APSGN. Methods:The clinical data of 100 children whose were clinically diagnosed with APSGN and admitted to the Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were collected and retrospectively analyzed.Seventy-three cases finally diagnosed with APSGN were included in the APSGN group and 27 cases with C 3G were classified into the C 3G group.The clinical manifestations, laboratory results, treatment and prognosis of the 2 groups of children were analyzed and compared by the t-test, Mann-Whitney U test and χ2 test. Results:Both APSGN and C 3G patients had a history of streptococcal infection at the early stage of the disease.There was no significant difference in the onset age and gender between the 2 groups (all P>0.05). The clinical manifestations of APSGN and C 3G at the early stage are sometimes difficult to distinguish.However, the incidence rates of gross hematuria (92.6%) and nephrotic proteinuria (66.7%) in the C 3G group were higher than those in the APSGN group (69.8%, 30.1%) ( χ2=5.583, 10.960; all P<0.05). The laboratory test results suggested that compared with the C 3G group, the APSGN group had higher albumin levels [(36.3±7.4) g/L vs.(28.9±6.8) g/L], but lower triglycerides [(1.2±0.6) mmol/L vs.(1.6±0.7) mmol/L], blood urea [(7.6±5.6) mmol/L vs.(14.7±16.3) mmol/L], blood creatinine [(66.2±45.2) μmol/L vs.(120.1±170.3) μmol/L], and urine protein levels [(43.5±58.5) g/24 h vs.(319.2±994.8) g/24 h] ( t=4.655, 2.738, 2.241, 1.624, 1.448; all P<0.05). As for treatment, the use rates of hormones and other immunosuppressants in the C 3G group were higher than those in the APSGN group (59.3% vs.12.3%, 29.6% vs.1.4%) ( χ2=23.15, 19.22; all P<0.05). The follow-up data revealed that compared with the APSGN group, the C 3G group took a longer time for gross hematuria and microscopic hematuria symptoms to disappear, proteinuria test to turn negative and complement C 3 to recover [51.1(14.3, 90.0) d vs.14.9(6.0, 15.5) d; 218.3(60.0, 277.5) d vs.65.5(27.0, 82.5) d; 127.9(60.0, 180.0) d vs.38.2(13.0, 53.6) d; 129.3(55.5, 225.0) d vs.39.1(24.0, 51.0) d] ( U=2.395, 2.730, 2.890, 3.054; all P<0.05). Conclusions:APSGN children with relatively severe clinical manifestations during the acute stage, especially with unrelieved nephrotic proteinuria, should be highly suspected with C 3G.Such patients should be treated with steroids and undergo renal biopsy and complement investigation if necessary, so as to identify the cause early, adjust the treatment and improve their prognosis.

Progress of C3 glomerulopathy / 国际儿科学杂志

C3 glomerulopathy is a rare disease of glomeruli mediated by abnormal activation of alternative complement pathway secondary to congenital genetic defects and acquired autoantibodies.Renal biopsy is the gold standard for diagnosing C3 glomerulopathy.C3 glomerulopathy encompasses both dense deposit disease and C3 glomerulonephritis.The main glomerular immunofluorescence staining is C3, with few or without immunoglobulins deposition, which is the obvious pathological feature.The clinical manifestations of C3 glomerulopathy are usually various, with limited detection methods and therapies and poor prognosis.This article mainly reviews the progress of C3 glomerulopathy in recent years, in order to improve clinical understanding of C3 glomerulopathy, and choose individualized therapy.

Pathology of C3 Glomerulopathy

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

Clinical and pathological characteristics of children with C3 glomerulopathy / 中华实用儿科临床杂志

Objective To investigate the clinicopathological features and treatment of children with C3 glomerulopathy (C3 G).Methods Seven children diagnosed as C3 G by clinical and pathological characteristics were enrolled in this study.The clinicopathological data and the prognosis were analyzed.Results Of the 7 cases,4 cases were female and 3 cases were male,with the mean age of (7.7-± 3.1) years old (1.5-10.4 years old) at onset,the duration from onset to renal biopsy was (3.4 ± 2.4) months (1-6 months) and 1 of them had a second renal biopsy 4.2 years later,and mean age was (8.4 ± 3.6) years old (1.8-13.3 years old) on diagnosis.Clinical features:among the 7 patients,6 cases had hematuria,among them 1 case had gross hematuria and 5 cases had microscopic hematuria;6 cases had low level of serum complement C3,5 cases had heavy proteinuria and low serum albumin,and anemia was observed in 2 cases respectively.Five cases had complement factor H and H factor antibody by examination,and 1 of them had low serum factor H,but none of them had serum antibody to factor H.Four cases had genetic evaluation,and only 1 case revealed risk variants in the C3 gene(R304R,T612T,V807V,A915A,P1632P)and CFH gene(p.H402Y,p.E936D).Clinically,4 cases were diagnosed as nephrotic syndrome of nephritis type,2 cases were diagnosed as nephritic syndrome,and 1 case was diagnosed as nephrotic syndrome of simple type.Immunofluorescence study showed that all the cases had intense deposition of C3,and 6 cases were accompanied by the deposition of immunoglobulin.Under light microscopy,3 cases showed the feature of membrane proliferative glomemlonephritis,2 cases with endocapillary prolifera-tive glomerulonephritis,1 case with mesangial proliferative glomerulonephritis,and 1 case with endoeapillary proliferative IgA nephropathy.Under electron microscopy,3 cases who had typical ribbon-like dense deposits in glomerular basement membrane were of dense deposit disease,and the rest were C3 glomerulonephritis.All patients had steroid and immune inhibitor treatment,and during the follow-up stage of (2.6 ± 1.8) years(1.1-5.6 years),4 cases showed normal urinalysis,2 cases had microproteinurine and microscopic hematuria,and 1 case had urinary protein ± to + + and microscopic hematuria.Conclusions C3G has variety of pathological-clinical manifestation.Interpretation of individual cases depends on integration of information from the biopsy together with clinical,serological,and genetic features.Patients with steroid and immune inhibitor treatment had some clinical improvement of their urinalysis.

Effectiveness of Cyclosporine in a 10-year-old Girl with C3 Glomerulopathy

C3 glomerulopathy (C3G) is a recently defined pathological entity characterized by C3 accumulation with absent or scant immunoglobulin deposition, leading to variable glomerular inflammation. The clinical presentation of patients with C3G is highly variable, as they may present with symptoms ranging from microscopic or mild proteinuria to full-blown nephrotic syndrome, with or without renal impairment. However, there is no consensus recommendation for specific treatment in children with C3G. Recently, new therapies have been suggested to target complement pathways, owing to an improvement in the understanding of the pathogenesis of C3G. C3G complement blockade with eculizumab, a monoclonal antibody targeted against complement C5, inhibits activation of the alternative complement pathway. We could not use eculizumab owing to its high price; thus, we administered oral prednisolone and mycophenolate mofetil (MMF). MMF was replaced with cyclosporine because proteinuria persisted, with a consistently low serum C3 level; we tapered off the prednisolone because of a Cushingoid appearance and amenorrhea. Thereafter, proteinuria improved, and the serum C3 level returned to normal. Thus, we report the effectiveness of cyclosporine in a patient with C3G and an inadequate response to prednisolone and MMF, who was detected via school urinary screening.

Glomerulonefritis C3: una nueva categoría de glomerulonefritis con implicaciones etiopatogénicas / C3 glomerulonephritis: a new category of glomerulonephritis with etiopathogenic implications / Glomerulonefrite C3: uma nova categoria de glomerulonefrite com envolvimentos etiopatogênicas

Introducción: las glomerulonefritis con depósitos exclusivos de la fracción C3 del complemento (GN-C3) pueden implicar alteración en la vía alterna de este. Objetivos: describir retrospectivamente una serie de casos de GN-C3 y determinar la frecuencia con que los pacientes continúan con alteraciones renales y/o hipocomplementemia. Métodos: se evaluaron las características histológicas y clínicas y la evolución de los 22 casos de GN-C3 diagnosticados entre 2004 y 2012 en el Departamento de Patología (Facultad de Medicina, Universidad de Antioquia). Resultados: 14 de los pacientes fueron niños y 12 fueron hombres; la mediana de edad fue de 13 años (rango: 3-65). Diez se presentaron como síndrome nefrítico, siete como GN rápidamente progresiva, tres como insuficiencia renal aguda, uno como insuficiencia renal crónica y uno como síndrome nefrótico-nefrítico; 21 tenían hipocomplementemia C3. Todas las biopsias mostraron GN proliferativa. Ocho pacientes tuvieron remisión completa; cuatro, alteraciones persistentes del uroanálisis; seis desarrollaron enfermedad renal crónica, en cinco de ellos terminal; en cuatro no hubo seguimiento. En nueve pacientes hubo seguimiento de los niveles séricos de C3 y en todos ellos se normalizaron entre 1 y 3 meses después de la biopsia. Conclusiones: las GN-C3 pueden producir alteraciones renales persistentes o recurrentes y evolucionar a la insuficiencia renal terminal. Es recomendable el seguimiento clínico a largo plazo, con mediciones repetidas de los niveles de C3.

Introduction: Glomerulonephritis with only deposits of C3 (GN-C3) could involve alteration on the complement alternative pathway. Objective: To describe retrospectively a series of GNC3 cases and to determine the frequency with which patients continue with renal alterations and/or hypocomplementemia. Methods: The 22 cases of GN-C3 diagnosed between 2004 and 2012 at the Department of Pathology, Faculty of Medicine, University of Antioquia (Medellin, Colombia) were included. Their histological and clinical characteristics and their outcome were evaluated. Results: 14 patients were children and 12 were males. Mean age was 13 years (range: 3-65). Ten presented as a nephritic syndrome, seven as a rapidly progressive GN, three as acute renal failure, one as chronic renal failure, and one as a nephrotic-nephritic syndrome. The C3 fraction of complement was low in 21 cases. All biopsies showed proliferative GN. There was complete remission in eight patients, persistent urinalysis alterations in four, chronic renal failure in six, five of them end-stage. No follow-up was done in four. In nine patients follow-up determination of C3 serum levels was done; in all of them they normalized between 1 to 3 months after biopsy. Conclusions: GN-C3 can produce persistent or recurrent kidney alterations and end-stage renal disease. Long-term follow-up with repeated determinations of C3 is advisable.

Introdução: as glomerulonefrite com depósitos exclusivos da fração C3 do complemento (GN-C3) podem implicar alteração na via alterna deste. Objetivos: descrever retrospectivamente uma série de casos de GN-C3 e determinar a frequência com que os pacientes continuam com alterações renais e/ ou hipocomplementemia. Métodos: avaliaram-se as características histológicas e clínicas e a evolução dos 22 casos de GN-C3 diagnosticados entre 2004 e 2012 no Departamento de Patologia (Faculdade de Medicina, Universidade de Antioquia). Resultados: 14 dos pacientes foram meninos e 12 foram homens; a média de idade foi de 13 anos (casta: 3-65). Dez se apresentaram como síndrome nefrítico, sete como GN rapidamente progressiva, três como insuficiência renal aguda, um como insuficiência renal crônica e um como síndrome nefrótico-nefrítico; 21 tinham hipocomplementemia C3. Todas as biopsias mostraram GN proliferativa. Oito pacientes tiveram remissão completa; quatro, alterações persistentes do uroanálise; seis desenvolveram doença renal crônica, em cinco deles terminal; em quatro não teve seguimento. Em nove pacientes teve seguimento dos níveis séricos de C3 e em todos eles se normalizaram entre 1 e 3 meses depois da biopsia. Conclusões: as GN-C3 podem produzir alterações renais persistentes.

Progress of C3 glomerulopathy / 中国小儿急救医学

C3 glomerulopathy is a group of diseases with immunofluorescence staining C3 along the glomerular capillary loops deposition,may be accompanied by other immunoglobulin deposition,but C3 sedi-mentary classic way was more than other immunoglobulin and complement activation ingredients ( such as C1q,C4). C3 glomerulopathy is a group of primary glomerular disease and relatively rare. This article mainly reviewed the pathological characteristic of C3 glomerulopathy,clinical manifestation,diagnosis and treatment, in order to improve clinical understanding of C3 glomerulopathy.

C3 glomerulopathy: Advances in diagnosis and treatment / 第二军医大学学报

C3 glomerulopathy is a recently defined disease category comprising several rare types of glomerulonephritis (GN), including dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and CFHRS nephropathy. These disorders share a common etiology involving dysregulation of the complement alternative pathway (AP), with genetic defects and/ or autoantibodies seen in a proportion of patients. Currently no consistently effective therapy has been found for C3 glomerulopathy; clinical evaluation of agents targeting specific components of the complement system is undergoing. The appropriate timing and duration of proposed therapies need to be further explored. This review focuses on the clinical and histological features, complement tests and treatments of C3 glomerulopathy.

The pathogenic mechanism of C3 glomerulopathy and its countermeasures / 解放军医学杂志

C3 glomerulopathy is a series of diseases of glomeruli mediated by abnormal activation of alternative complement pathway. A series of researches have revealed in recent years that there are diversity and multiplicity of pathogenic mechanism in the pathogenesis of C3 glomerulopathy. The pathogenic mechanism of C3 glomerulopathy may be different in different individuals and types of disease. Congenital genetic defects and/or acquired autoantibodies may be found in the same individual. Individualized therapy should be given to individual patient in order to target different pathogenic mechanisms. Chinese herbal medicine, Tripterygium wilfordii, shows promise as a potential therapeutic agent for C3 glomerulopathy. The pathogenic mechanism and countermeasures for C3 glomerulopathy have been reviewed in present paper.

Heterogeneity of the clinical manifestations and pathology features in c3 glomerulopathy / 解放军医学杂志

C3 glomerulopathy is a kind of glomerular diseases mediated by abnormal activation of alternative complement pathway. As diversity and multiplicity of pathogenic mechanism, heterogeneity exists in the clinical manifestation and pathological features of C3 glomerulopathy. The clinical manifestation of the disease may be shown as abnormality in urine, hypertension, hematuria, nephrotic syndrome, nephritic syndrome, renal insufficiency, etc. Membranoproliferative glomerulonephritis, mesangial proliferation, crescent formation, focal segmental necrosis, diffuse hyperplasia and exudative lesions, etc may be found in renal biopsies. Also, the prognosis of C3 glomerulopathy is not uniform. The clinical manifestations and pathological features of C3 glomerulopathy were reviewed in the present paper.