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.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Pharmacogenetic testing improves treatment responses in patients with PLA2R-related membranous nephropathy / 南方医科大学学报

OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.

Bioinformatics analysis and validation of key genes in transformation of idiopathic membranous nephropathy to end-stage renal disease and traditional Chinese medicines for prevention and treatment / 中国中药杂志

This study used bioinformatics analysis to screen out key genes involved in the transformation of idiopathic membranous nephropathy to end-stage renal disease and to predict targeted Chinese herbs and medicines and active ingredients with preventive and curative effects. The GSE108113 microarray of idiopathic membranous nephropathy and GSE37171 microarray of were downloaded from the comprehensive gene expression database, and 8 homozygous differentially expressed genes for the transformation of idiopathic membranous nephropathy into end-stage renal disease of were screened out by R software. GraphPad Prism was used to verify the expression of homozygous differentially expressed genes in GSE115857 microarray of idiopathic membranous nephropathy and GSE66494 microarray of chronic kidney disease, and 7 key genes(FOS, OGT, CLK1, TIA1, TTC14, CHORDC1, and ANKRD36B) were finally obtained. The Gene Ontology(GO) analysis was performed. There were 209 functions of encoded proteins, mainly involved in regulation of RNA splicing, cytoplasmic stress granule, poly(A) binding, etc. Thirteen traditional Chinese medicines with the effect of preventing the transformation of idiopathic membranous nephropathy to end-stage renal disease were screened out from Coremine Medical database, including Ginseng Radix et Rhizoma, Lycopi Herba, and Gardeniae Fructus, which were included in the Chinese Pharmacopoeia(2020 edition). The active ingredient quercetin mined from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) had ability to dock with the key gene FOS-encoded protein molecule, which provided targets and research ideas for the development of new traditional Chinese medicines.

Network Meta-analysis of Chinese patent medicines in treatment of idiopathic membranous nephropathy / 中国中药杂志

This study aimed to systematically evaluate the efficacy and safety of different Chinese patent medicines in the treatment of idiopathic membranous nephropathy. The relevant randomized controlled trial(RCT) was retrieved from PubMed, EMbase, Cochrane Library, CNKI, SinoMed, Wanfang, and VIP with the time interval from database inception to December 2022. The Cochrane risk of bias assessment tool was employed to evaluate the quality of the included RCT, and Stata 15.0 and GEMTC to perform the Bayesian network Meta-analysis. Finally, 51 RCTs were included, involving 9 Chinese patent medicines and 3 591 patients. The results of network Meta-analysis showed that in terms of the total effective rate and the increase in plasma albumin, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Bailing Capsules + conventional western medicine, and Tripterygium Glycosides Tablets + conventional western medicine. In terms of reducing 24-hour urine total protein, the top three interventions were Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine, Shenfukang Capsules +conventional western medicine, and Huangkui Capsules + conventional western medicine. In terms of reducing serum creatinine, the top three interventions were Shenfukang Capsules + conventional western medicine, Bailing Capsules + conventional western medicine, and Zhengqing Fengtongning Sustained Release Tablets + conventional western medicine. In terms of safety, Chinese patent medicines combined with conventional western medicine had fewer adverse reactions than the control group. The results suggest that Chinese patent medicines combined with conventional western medicine can improve the therapeutic effect on idiopathic membranous nephropathy, and differentiated medications can be adopted according to the specific symptoms of patients in clinical treatment. Further validation needs to be carried out in the future with multi-center, large-sample, and high-quality RCT.

Manejo de la nefropatía membranosa idiopática con ciclofosfamida endovenosa / Manejo de la nefropatía membranosa idiopática con ciclofosfamida endovenosa

Introducción: las enfermedades glomerulares primarias ocupan la tercera causa de enfermedad renal crónica, siendo el origen más común de síndrome nefrótico en Colombia la nefropatía membranosa (NM). El tratamiento de la NM con ciclofosfamida endovenosa es una opción terapéutica, que no ha sido descrita en nuestra población. Objetivo: determinar la respuesta al tratamiento con ciclofosfamida endovenosa en la NM idiopática en el Hospital de San José de Bogotá en el periodo enero 2000 a enero 2019. Metodología: estudio tipo serie de casos donde se incluyeron todos los pacientes adultos con diagnóstico de NM idiopática por biopsia renal tratados con ciclofosfamida endovenosa en el periodo descrito Resultados: ocho pacientes se incluyeron en el estudio de los cuales 50% eran mujeres, la mediana de edad de presentación fue 32,5 (RIQ:26-45) años. El 100% de los pacientes presentaron remisión parcial o completa, distribuidos así: 62,5% completa y 37,5% parcial. La mediana en el aumento de la tasa de filtración glomerular posterior al uso de ciclofosfamida endovenosa fue 9 (RIQ: 1-20,2) mL/min/1.73 m2. La sobrevida renal fue 100% y el porcentaje de recaída 12,5%. Conclusiones: el uso mensual de ciclofosfamida endovenosa es una opción en el manejo de la NM idiopática con un porcentaje de remisión parcial o completa de 100%, utilizando una dosis mediana acumulada de 93 (RIQ: 65,6-125) mg/k.

Introduction: primary glomerular diseases represent the third cause of chronic kidney disease, being membranous nephropathy (MN) the most frequent cause of nephrotic syndrome in Colombia. Intravenous cyclophosphamide is a treatment option for MN, which has not been described in our population. Objective: to determine the response of idiopathic membranous nephropathy (IMN) to IV cyclophosphamide at Hospital de San José de Bogotá from January 2000 to January 2019. Methodology: case series study which included all adult patients with IMN diagnosed by renal biopsy treated with IV cyclophosphamide in the described period. Results: eight patients were included in the study of which 50% were women, median age at presentation was 32.5 (IQR: 26-45) years. 100% of patients experienced partial or complete remission, as follows: 62.5% complete remission and 37.5% partial remission. Increase in the median glomerular filtration rate after the use of IV cyclophosphamide was 9 (IQR: 1-20.2) mL/min/1.73 m2. Renal survival rate was 100% and the relapse rate was 12.5%. Conclusions: monthly IV cyclophosphamide is a treatment option for IMN, attaining 100% partial or complete remission, using a median cumulative dose of 93 (IQR: 65.6-125) mg/k.

Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis / 中国针灸

OBJECTIVE@#To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis.@*METHODS@#A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups.@*RESULTS@#The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (@*CONCLUSION@#Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

A rare case of PLA2R- and THSD7A-positive idiopathic membranous nephropathy / Positividade tecidual dupla para PLA2R e THSD7A em nefropatia membranosa idiopática: raro relato de caso

ABSTRACT Idiopathic membranous nephropathy (IMN) is a frequent cause of nephrotic syndrome in adults. In terms of etiology, the condition may be categorized as primary/idiopathic or secondary. Literature on the pathophysiology of IMN has indicated the presence of autoantibodies (PLA2R and THSD7A) directed against podocyte antigens. The detection of antibodies against a domain favors IMN. The presence of autoantibodies against one of the domains would in theory exclude the possibility of there being autoantibodies against the other domain. However, cases of patients with PLA2R- and THSD7A-positive disease have been recently reported, showing that antibodies against two targets may be concomitantly produced via yet unknown pathophysiological mechanisms. This study reports the case of a 46-year-old male patient with nephrotic-range proteinuria, hematuria, hypoalbuminemia, and hypercholesterolemia submitted to biopsy and histopathology examination (LM, IF, IHC, and EM) eventually diagnosed with PLA2R- and THSD7A-positive IMN associated with IgA nephropathy, stressing our experience with the use of IgG subclasses, PLA2R, and THSD7A in the workup for MN and the relevance of adopting a broad and adequate approach to elucidating and acquiring knowledge of the pathophysiology of IMN.

RESUMO A Nefropatia Membranosa Idiopática (NMi) é uma frequente causa de síndrome nefrótica em adultos e sua etiologia pode ser estratificada em primária/idiopática ou secundária. O conhecimento da fisiopatologia da NMi sugeriu a presença de autoanticorpos (PLA2R e a THSD7A) direcionados contra antígenos existentes nos podócitos. A detecção de anticorpos contra um domínio favorece NMi. A presença de autoanticorpos contra um desses domínios autoexcluiria a possibilidade de autoanticorpos contra o outro domínio; no entanto, recentemente foram descritos casos que apresentaram dupla positividade para PLA2R e THSD7A, comprovando que, por mecanismos fisiopatológicos ainda não conhecidos, raramente pode existir produção concomitante de anticorpos contra os dois alvos. O presente estudo tem por objetivo relatar o caso de um paciente de 46 anos de idade, do sexo masculino, que apresentou quadro de proteinúria nefrótica, hematúria, hipoalbuminemia e hipercolesterolemia submetido a biópsia e exame histopatológico (ML, IF, IHQ e ME), confirmando um caso raro de NMi com positividade dupla para os anticorpos anti-PLA2R e anti-THSD7A e associação à nefropatia por IgA, mostrando nossa experiência com a utilização de subclasses de IgG, PLA2R e THSD7A na rotina laboratorial para a investigação da GNM e enfatizando a importância de uma abordagem ampla para adequada elucidação e conhecimento dos mecanismos fisiopatológicos na NMi.

Focal and Segmental Glomerulosclerosis and Membranous Nephropathy overlapping in a patient with Nephrotic Syndrome: a case report / Glomeruloesclerose Segmentar e Focal e Nefropatia Membranosa sobrepostas em paciente com Síndrome Nefrótica: relato de caso

Abstract Introduction: Some cases of membranous nephropathy (MGN) present focal segmental glomerulosclerosis (FSGS) typically associated with disease progression. However, we report a case of a patient who seemed to have MGN and FSGS, both primary. Case presentation: A 17-year-old female, Caucasian, presenting lower extremity edema associated with episodes of foamy urine and high blood pressure, had physical and laboratorial exams indicating nephrotic syndrome. A renal biopsy was performed and focal and segmental glomerulosclerosis were observed under light microscopy in some glomeruli presented as tip lesion, and in others it was accompanied by podocyte hypertrophy and podocyte detachment in urinary space, compatible with podocytopathy FSGS. Besides, there were thickened capillary loops with basement membrane irregularities due to "spikes" compatible with MGN stage II. Immunofluorescence showed finely granular IgG, IgG4, and PLA2R deposits in capillary loops and, in electron microscopy, subepithelial deposits and foot process effacement. These morphological findings are compatible with FSGS and MGN stage II. Conclusions: In the present case, clinical and morphological characteristics showed a possible overlap of primary FSGS and MGN as focal and segmental glomerulosclerosis does not seem to be related with MGN progression but with the podocytopathy FSGS.

Resumo Introdução: Alguns casos de nefropatia membranosa (NM) apresentam glomeruloesclerose segmentar e focal (GESF) tipicamente associada a progressão da doença. Contudo, relatamos o caso de uma paciente que parece ter NM e GESF, ambas primárias. Apresentação do caso: Uma jovem branca de 17 anos de idade com edema de membros inferiores associado a episódios de urina espumosa e hipertensão apresentou-se com achados físicos e laboratoriais sugestivos de síndrome nefrótica. Foi realizada biópsia renal. GESF foi observada por microscopia de luz em alguns glomérulos que apresentavam lesões de ponta, enquanto em outros o achado era acompanhado por hipertrofia podocitária e descolamento de podócitos no espaço urinário, compatíveis com podocitopatia GESF. Além disso, as alças capilares estavam espessadas com irregularidades na membrana basal devido a "espículas" compatíveis com NM estágio II. Imunofluorescência revelou depósitos finamente granulares de IgG, IgG4 e PLA2R nas alças capilares. Microscopia eletrônica exibiu depósitos subepiteliais e apagamento de pedicelos. Tais achados morfológicos são compatíveis com GESF e NM estágio II. Conclusões: No presente caso, as características clínicas e morfológicas revelaram uma possível sobreposição de GESF primária e NM, uma vez que a glomeruloesclerose segmentar e focal não parece estar relacionada com a progressão da NM, mas com a podocitopatia GESF.

Clinical significance of Mtype phospholipase A2 receptor and thrombospondin Type 1 domaincontaining 7A in primary membranous nephropathy / 中南大学学报(医学版)

OBJECTIVES@#To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis.@*METHODS@#Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.@*RESULTS@#The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group.@*CONCLUSIONS@#PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.

Glomerulopatía membranosa con glomerulonefritis necrosante. Una asociación infrecuente / Membranous glomerulopathy with necrotizing glomerulonephritis. An infrequent association

Resumen Antecedentes: la asociación entre glomerulopatía membranosa y glomerulonefritis necrosante crescéntica es infrecuente: 0.4%, confiriendo un escenario de peor pronóstico. Se requieren estudios que precisen el esquema de tratamiento óptimo, sin embargo, el rápido inicio de terapia inmunosupresora impacta en la preservación de la función renal. Objetivo: exponer un caso en el cual se presenta esta asociación y tiene adecuada respuesta con el tratamiento realizado. Métodos: en este artículo se presenta un caso de una mujer con síndrome nefrótico a quien se le documenta glomerulopatía membranosa con proliferación extracapilar confirmada con biopsia renal, sin evidencia de autoinmunidad, neoplasia ni proceso infeccioso. Tras el diagnóstico se inició manejo con metilprednisolona y ciclofosfamida con adecuada evolución, sin deterioro de la función renal y con mejoría de proteinuria. Conclusión: la presencia de proliferación extracapilar da peor pronóstico en los pacientes con glomerulopatía membranosa, el inicio oportuno del tratamiento es fundamental. (Acta Med Colomb 2019; 44: 39-42).

Abstract Background: the association between membranous glomerulopathy and crescentic necrotizing glomerulonephritis is infrequent: 0.4%, conferring a worst prognosis scenario. Studies that require the optimal treatment scheme are required; however, it has been described that the rapid onset of immunosuppressive therapy impacts on the preservation of renal function. Objective: to present a case in which this association is presented and has an adequate response to the performed treatment. Methods: in this article, a case of a woman with nephrotic syndrome with a documented membranous glomerulopathy with extracapillary proliferation confirmed by renal biopsy, without evidence of autoimmunity, neoplasia or infectious process is presented. After the diagnosis, treatment with methylprednisolone and cyclophosphamide was started with adequate evolution, without deterioration of renal function and with improvement of proteinuria. Conclusion: the presence of extracapillary proliferation gives worse prognosis in patients with membranous glomerulopathy. The timely initiation of treatment is essential. (Acta Med Colomb 2019; 44: 39-42).

Obesidad y riñón / Obesity and the kidney

RESUMEN Introducción: La obesidad es un problema de salud mundial y su frecuencia se está incrementando tanto en adultos como en niños. Una de sus complicaciones es la glomerulopatía asociada a la obesidad. Objetivo: Informar acerca de esta enfermedad y la actitud del pediatra para tratar de evitarla. Métodos: Revisión de la literatura médica más reciente sobre la enfermedad y el incremento de la obesidad en la edad pediátrica en las bases de datos PubMed, SciELO y LILACS. Se utilizaron las palabras clave: glomerulopatía relacionada con la obesidad, obesidad y sobrepeso en el niño, tratamiento de la obesidad. Resultados: La obesidad en el niño es en alto porcentaje de causa nutricional y en esta condición los factores ambientales y socioculturales juegan importante papel. La predisposición a padecer la glomerulopatía de la obesidad comienza desde la niñez. El tratamiento de los pediatras en estos casos estará dirigido a la prevención de la enfermedad puesto que se puede desarrollar en la adultez. Cuando fracasan las medidas preventivas, queda la posibilidad de la cirugía bariátrica con poca experiencia en la edad pediátrica y retos éticos importantes y a pesar de que pudiera ser una alternativa de tratamiento, no es aceptada hasta el presente en forma amplia. Conclusiones: La glomerulopatía de la obesidad, por lo general, no aparece hasta la adultez, pero es necesario prevenirla desde la edad pediátrica y para su prevención los pediatras deben estar atentos a los factores de riesgo que pueden aparecer desde las primeras etapas de la vida(AU)

ABSTRACT Introduction: Obesity is a global health problem and its frequency is increasing as much as in adults than in children. One of its complications is glomerulopathy associated to obesity. Objective: To inform on this disease and the attitude of pediatricians towards this trying to avoid it. Methods: Reviewing of the most recent medical literature on this disease and the increase of obesity in the pediatric age in PubMed, SCIELO and LILACS databases. The keywords used for the search were: glomerulopathy related to obesity, obesity and overweight in children, and obesity treatment. Results: Obesity in children is in a high percentage due to nutritional causes and in this disease environmental and sociocultural factors play an important role. The predisposition to suffer from glomerulopathy by obesity starts in childhood. The treatment prepared by the pediatricians in these cases will be directed to the prevention of the disease because it can be developed in adulthood. When preventive measures fail, there is the possibility of performing a bariatric surgery, having in this regard few experiences in the pediatric ages and important ethical challenges; and instead of being an alternative treatment, it is not widely accepted. Conclusions: Generally, glomerulopathy of obesity doesn't appear until adulthood, but it is necessary to prevent it since the pediatric age; and for its prevention pediatricians must be attentive to the risk factors that can appear from the earliest stages of life(AU)

Glomerulopatías combinadas: comunicación de 2 casos pediátricos / Combined glomerulopathies: two pediatric cases

La combinación de glomerulopatías es infrecuente en la población pediátrica. Su presencia debe ser sospechada en aquellos pacientes con una enfermedad glomerular de curso clínico atípico. La influencia a largo plazo sobre el deterioro funcional renal permanece incierta. Se presentan dos niños con características histológicas de glomerulopatía combinada.

Combined glomerulopathy is infrequent in pediatric patients. Its presence should be suspected in those patients with glomerulophaties with atypical course. The influence on the long-term renal impairment remains uncertain. Here we report two children with histological findings of combined glomerulopathy.

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy Volume 37, Issue 3, September 2018, Pages 248–256

In the article, there was an error in Figure 3.

Anti-phospholipase A2 receptor antibodies in membranous nephropathy

No abstract available.

Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy

BACKGROUND: Phospholipase A2 receptor (PLA2R) has been identified as a major autoantigen in primary membranous nephropathy (MN). We evaluated the association between anti-PLA2R antibodies and clinical outcome in Korean patients with primary MN. METHODS: A total of 66 patients with biopsy-proven MN were included. Serum level of anti-PLA2R antibodies was measured by enzyme-linked immunosorbent assay. Biochemical parameters were estimated initially and at follow-up. RESULTS: Anti-PLA2R antibodies were detected in 52.1% and 27.8% of patients with primary and secondary MN, respectively. Forty-eight patients with primary MN were grouped based on presence or absence of anti-PLA2R antibodies. Proteinuria was more severe in anti-PLA2R-positive patients than in anti-PLA2R-negative patients (urine protein/creatinine ratio 7.922 ± 3.985 g/g vs. 4.318 ± 3.304 g/g, P = 0.001), and anti-PLA2R antibody level was positively correlated with proteinuria. The incidence of chronic kidney disease stage ≥ 3 was higher in anti-PLA2R-positive patients compared with anti-PLA2R-negative patients (P = 0.004). The probabilities of spontaneous remission were higher in anti-PLA2R-negative patients compared with anti-PLA2R-positive patients (P < 0.001). Multivariate analysis demonstrated that anti-PLA2R antibodies are an independent risk factor for developing chronic kidney disease stage ≥ 3 and for not reaching spontaneous remission. CONCLUSION: Detection of anti-PLA2R antibodies at diagnosis in patients with primary MN can predict prognosis and guide treatment decisions.

The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial

BACKGROUND: Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073). METHODS: A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared. RESULTS: The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, −0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks. CONCLUSION: In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (www.ClinicalTrials.gov NCT01282073).

Complement System and C4d expression in cases of Membranous nephropathy / Sistema complemento e expressão de C4d em casos de Glomerulopatia Membranosa

Abstract Introduction: Membranous nephropathy (MN) is one of the major causes of nephrotic syndrome. The complement system plays a key role in the pathophysiology of MN. Objectives: To identify the complement pathway possibly activated in MN cases and correlate the presence of C4d with more severe clinical and histological markers. Methods: Sixty nine cases from renal biopsy with membranous nephropathy were investigated. The presence of C1q was analyzed by direct immunofluorescence; and expression of C4d by immunohistochemistry. Clinical and epidemiological data were obtained upon biopsy request. Results: The presence of focal segmental glomerulosclerosis, global glomerulosclerosis, vascular lesions and tubulointerstitial fibrosis were collected by anatomopathological report. C4d(+) was found in 58 (84%), and C1q(+) was found in 12 (17%) of the cases. Twelve patients had C4d(+)/C1q(+), 46 had C4d(+)/C1q(-), and 11 patients had C4d(-)/C1q(-), probably indicating the activation of the classical, lectin and alternative pathways, respectively. Conclusion: C4d was associated with increased interstitial fibrosis, but not with clinical markers of poor prognosis. Through the deposition of C4d and C1q we demonstrated that all complement pathways may be involved in MN, highlighting the lectin pathway. The presence of C4d has been associated with severe tubulointerstitial lesions, but not with clinical markers, or can be taken as a universal marker of all cases of MN.

Resumo Introdução: A Glomerulopatia membranosa (GM) é uma das principais causas da síndrome nefrótica. O sistema do complemento desempenha um papel chave na fisiopatologia do GM. Objetivos: Identificar a via do complemento possivelmente ativada nos casos de GM e correlacionar a presença de C4d com marcadores clínicos e histológicos mais graves. Métodos: Foram investigados 69 casos de biópsia renal com GM. A presença de C1q foi analisada por imunofluorescência direta e a expressão de C4d por imunohistoquímica. Dados clínicos e epidemiológicos foram obtidos mediante solicitação de biópsia renal. Resultados: A presença de glomerulosclerose segmentar focal, glomeruloesclerose global, lesões vasculares e fibrose tubulointersticial foi coletada por relato anatomopatológico. C4d (+) foi encontrado em 58 (84%), e C1q (+) foi encontrado em 12 (17%) casos. Doze pacientes tinham C4d (+)/C1q (+), 46 tinham C4d (+)/C1q (-) e 11 pacientes tinham C4d (-)/C1q (-), indicando provavelmente a ativação da via clássica, da lectina e da alternativa, respectivamente. Conclusão: O C4d foi associado ao aumento da fibrose intersticial, mas não com marcador clínico de mau prognóstico. Através da deposição de C4d e C1q, demonstrou-se que todas as vias do complemento podem estar envolvidas em GM, destacando a via da lectina. A presença de C4d tem sido associada a lesões tubulointersticiais graves, mas não com marcadores clínicos, ou pode ser tomada como um marcador universal de todos os casos de GM.

Recovery of renal function after bilateral renal vein thrombo sis episode as complication of membranous glomerulopa thy: case report / Recuperação da função renal após episódio de trombose de veia renal bilateral como complicação da glomerulopatia membranosa: relato de caso

ABSTRACT Renal vein thrombosis (RVT) is a complication often associated with nephrotic syndrome. It occurs due to a state of hypercoagulability common in the diseases that attend to this syndromic diagnosis. It should be suspected whenever there is nephrotic syndrome associated with sudden flank pain, hematuria and worsening of proteinuria. Bilateral RVT also presents with frequently oliguric renal dysfunction. This case reports a 33-year-old patient hospitalized for a nephrotic syndrome, with etiologic investigation suggestive of primary membranous glomerulopathy, which evolved with bilateral RVT associated with deterioration of renal function and need for renal replacement therapy. He promptly performed angiography with thrombectomy and thrombolysis, evolving with recovery of renal function in two weeks.

RESUMO A trombose de veia renal (TVR) é uma complicação muitas vezes associada à síndrome nefrótica. Ocorre devido a um estado de hipercoagulabilidade comum nas enfermidades que cursam com esse diagnóstico sindrômico. Deve ser suspeitada sempre que houver síndrome nefrótica associada à dor súbita em flanco, hematúria e piora da proteinúria. TVR bilateral cursa, ainda, com disfunção renal frequentemente oligúrica. Esse caso reporta um paciente de 33 anos internado por um quadro de síndrome nefrótica, com investigação etiológica sugestiva de glomerulopatia membranosa primária, que evoluiu com TVR bilateral associada à deterioração da função renal e necessidade de terapia substitutiva renal. Realizou, prontamente, angiografia com trombectomia e trombólise, evoluindo com recuperação da função renal em duas semanas.

O papel da IgG4 na fisiopatogenia da nefropatia membranosa idiopática: estado da arte / The role of IgG4 in the physiopathology of idiopathic membranous nephropathy: state of the art

Nefropatia membranosa idiopática é uma causa de síndrome nefrótica cuja etiopatogenia não está completamente esclarecida. Trata-se de uma doença imunologicamente mediada, na qual a deposição de imunocomplexos decorre da reação antígenoanticorpo in situ, na região subepitelial glomerular. A maioria dos antígenos envolvidos identificados são alvos da IgG4, subclasse predominante em imunofluorescências renais na nefropatia membranosa idiopática, em contraste com as formas secundárias da doença, nas quais IgG1, IgG2 e IgG3 prevalecem. Apesar da IgG4 ser um subtipo de imunoglobulina com baixa capacidade de ativação do complemento, há várias evidências deste envolvimento na glomerulopatia (GMP). Esses dados, em conjunto com achados de depósitos glomerulares de lectina ligadora de manose, um dos principais componentes da via das lectinas do complemento, podem sugerir que tanto a via da lectina como a IgG4 estão envolvidas nesta patologia. Os motivos que desencadeiam a formação dos imunocomplexos e a ativação das vias do complemento nesta doença são incertos. A hipótese mais aceita é a de que a nefropatia membranosa idiopática resulte do conjunto de três condições: presença de proteínas com conformações alteradas que passam a atuar como autoantígenos, anticorpos do tipo IgG4 contra estes antígenos, e susceptibilidade genética. O objetivo foi verificar o possível papel da IgG4 na etiopatogenia da nefropatia membranosa primária segundo o que foi publicado até o momento na base de dados MEDLINE/PubMed, a partir de uma revisão narrativa.

Idiopathic membranous nephropathy is a frequent cause of nephrotic syndrome and its etiopathogenesis is not fully elucidated. In this immune mediated disease, the deposition of immune complexes is the result of an antigen-antibody reaction in situ, in the glomerular subepithelial region. Most of the antigens involved and so far identified are targets of IgG4, a predominant IgG subclass in renal immunofluorescence analysis of idiopathic membranous nephropathy, in contrast with secondary forms of the disease, in which IgG1, IgG2 and IgG3 are prevalent. Even though IgG4 is an immunoglobulin subclass with low complement activation capacity, there is abundant evidence of its involvement in the glomerulopathy. These data, together with findings of glomerular deposition of mannose-binding lectin ­ a major component of the lectin pathway in the complement system ­ may suggest that both the lectin pathway and IgG4 are involved in this pathology. The reasons behind the formation of immune complexes and the activation of complement pathways in this disease are unknown. The most widely accepted hypothesis is that idiopathic membranous nephropathy stems from a combination of three conditions: presence of proteins with altered conformations, which start to act as autoantigens; IgG4 antibodies against these antigens; and genetic susceptibility. The objective of this narrative review was to analyze the possible role of IgG4 in the etiopathogenesis of primary idiopathic membranous nephropathy based on articles published to date in the MEDLINE/PubMed database.