Hepatitis B virus X protein promotes podocyte pyroptosis in hepatitis B virus-associated glomerulonephritis by down-regulating microRNA -223 targeting NLRP3 inflammasome / 中华肝脏病杂志

Objective: To investigate the potential function and related mechanism of microRNA-223 (miRNA-223) in the podocyte pyroptosis of hepatitis B virus (HBV)-associated glomerulonephritis induced by HBV X protein (HBx). Methods: HBx-overexpressing lentivirus was transfected into human renal podocytes to mimic the pathogenesis of HBV-GN. Real-time fluorescence quantitative PCR and Western blotting experiments were used to detect the mRNA and protein expression of pyroptosis-related proteins [nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1], and inflammatory factors (interleukin-1β and interleukin-18), respectively.TUNEL staining and flow cytometry were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression of podocytes biomarkers desmin and nephrin; Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to measure caspase-1 activity. The dual luciferase reporter gene assay was used to verify the downstream target of miRNA-223. Podocytes were divided into the following nine groups: control group (no special treatment), empty plasmid group (transfected with empty plasmid), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+miRNA-223 mimic group (transfected with HBx overexpression lentivirus and miRNA-223 mimic), HBx overexpression+miRNA-223 inhibitor group (transfected with HBx overexpression lentivirus and miRNA-223 inhibitor), HBx overexpression+miRNA-223 mimic+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 mimic+ NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 mimic and NLRP3 siRNA), HBx overexpression+miRNA-223 inhibitor+NLRP3 group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 overexpression plasmid), HBx overexpression+miRNA-223 inhibitor+NLRP3 siRNA group (transfected with HBx overexpression lentivirus, miRNA-223 inhibitor and NLRP3 siRNA). Results: miRNA-223 was down-regulated in HBx overexpression group compared with the control group (P < 0.05). TUNEL and immunofluorescence staining showed that NLRP3 knockdown attenuated podocyte injury and pyroptosis induced by HBx overexpression (P < 0.05). Dual luciferase reporter gene assay demonstrated that NLRP3 was one of the downstream targets of miRNA-223. Rescue experiments revealed that NLRP3 overexpression weakened the protective effect of miRNA-223 in podocyte injury (P < 0.05). The addition of miRNA-223 mimic and NLRP3 siRNA decreased the expression of NLRP3 inflammasome and cytokines, and reduced the number of pyroptosis cells induced by HBx overexpression (all P < 0.05); The addition of miRNA-223 inhibitor and NLRP3 overexpression plasmid significantly increased the expression of NLRP3 inflammasome and cytokines, caspase-1 activity, and the number of pyroptosis cells (all P < 0.05). Conclusion: HBx may promote podocyte pyroptosis of HBV-GN via downregulating miRNA-223 targeting NLRP3 inflammasome, suggesting that miRNA-223 is expected to be a potential target for the treatment of HBV-GN.

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.

Organizing Pneumonia in A Patient Double-Positive for ANCA and Anti-GBM Antibodies: A Case Report / 中国医学科学杂志(英文版)

Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.

Bilateral En-Block Horseshoe Kidney Laparoscopic Nephrectomy / Nefrectomía bilateral en bloque en riñón en herradura

Horseshoe kidney (HSK) has a prevalence of 1 in every 500 individuals. The management of patients with HSK is usually conservative, except in the presence of symptoms such as obstruction, stones, glomerulopathies, and tumors. In the following case report, we describe how a bilateral en-block transmesenteric laparoscopic nephrectomy in supine position was performed. A 5-year-old boy, with proximal hypospadias and early onset of chronic kidney disease due to focal segmental glomerulosclerosis on biopsy, underwent a genetic molecular evaluation that confirmed a pathogenic mutation at the WT-1 gene. Due to the increased risk of developing Wilms tumor, he underwent a bilateral transmesenteric nephrectomy. In a five-minute video, we describe how we performed an en-block transperitoneal and transmesenteric laparoscopic nephrectomy with special attention to patient positioning, including the feasibility of performing the dissection of the left renal hilum and isthmus with the patient in supine with no need for repositioning, and then moving to the dissection of the right renal hilum and completion of the procedure. The case herein reported enables us to describe the technical key-points to perform a bilateral en-block laparoscopic nephrectomy with shorter operative time and reduction of blood loss by preserving the entire specimen, without the need for an isthmus transection.

El riñón en herradura (RH) tiene una prevalencia de 1 en cada 500 individuos. El manejo del RH es usualmente conservador, excepto cuando genera síntomas como obstrucción, litiasis, glomerulopatías o tumores. Con este reporte de caso, describimos como se realizó una nefrectomia bilateral en bloque transmesentérica en un paciente con riñón en herradura. Un paciente de 5 años de edad, con hypospadias proximal y desarrollo temprano de enfermedad renal crónica por glomeruloesclerosis focal segmentaria, fue sometido a un estudio molecular que confirmó la presencia de una mutación en el gen WT-1. Dado el alto riesgo de desarrollar tumor de Wilms, se decidió realizar una nefrectomía transperitoneal laparoscópica bilateral. En un video de cinco minutos, describimos como se realizó una nefrectomía transperitoneal y transmesentérica en bloque, con especial atención al posicionamiento del paciente, incluso la viabilidad de realizar la disección del hilio renal izquierdo y el istmo con el paciente en supino, sin necesidad de reposicionarlo, y, después, la disección del hilio renal derecho y el fin del procedimiento. El caso reportado nos permite describir los puntos clave técnicos para realizar una nefrectomía laparoscópica bilateral en bloque con un tiempo operativo más corto y reducción del sangrado al preservar todo el espécimen, sin la necesidad de realizar la transección del istmo.

Intercambio plasmático terapéutico por plasmafiltración: experiencia de 11 años de un centro / Therapeutic plasma exchange: experience in 102 patients

BACKGROUND: Therapeutic Plasma Exchange (TPE) is a procedure in which plasma and harmful macromolecules are separated from the rest of the blood components by centrifugation or filtration through membranes and are replaced with solutions with albumin and/or plasma. AIM: To communicate our experience using TPE by filtration. MATERIAL AND METHODS: Review of records of 655 TPE sessions performed in 102 patients aged 50 ± 18 years (64% women). The requirement of renal replacement therapy (RRT) and seven days and one year mortality were recorded. RESULTS: Forty five percent of patients had hypertension or diabetes. The main indications for TPE were pulmonary-renal syndrome (PRS) (62%) and antibody mediated graft rejection (29%), followed by neurological diseases (36%). Fifteen percent of patients required RRT for one year. Mortality at seven days and one year was 20 and 30%, respectively. Out of the total of deaths associated with kidney diseases, 88% corresponded to PRS and ANCA vasculitis. The main complications were thrombocytopenia in 41%, hypocalcemia in 18%, and hypotension in 16%. CONCLUSIONS: In our experience, TPE by filtration is a safe technique, with mild and preventable complications. Despite this, the reported mortality is high, which reflects the severity of the diseases that motivated the indication for TPE.

Renal Amyloidosis Secondary to ANCA-Associated Vasculitis: A Case Report / 中国医学科学杂志(英文版)

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare. Here, we reported a 77-year-old woman with ANCA-associated vasculitis. Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis, and electron microscopy showed amyloid deposition in the mesangial area. Immunofluorescence revealed kappa light chain and lambda light chain negative. Bone marrow biopsy revealed no clonal plasma cell. Finally, she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.

Síndrome pulmón-riñón en pacientes con hallazgos incidentales de agentes infecciosos / Pulmonary-renal syndrome in patients with incidental findings of infectious agents

El síndrome pulmón-riñón (SPR) o síndrome reno-pulmonar es la combinación de glomerulonefritis aguda rápidamente progresiva (GNARP) y hemorragia alveolar difusa (HAD) de causa autoinmune. El SPR fue inicialmente descrito por Goodpasture en el contexto del síndrome anti-membrana basal glomerular (MBG). Actualmente, las vasculitis asociadas a ANCA (VAA) explican el 60% (rango 56­77.5%) de casos, el síndrome de Goodpasture el 15% (12.5­17.5%), y un 10% de casos se deben a otras causas. El SPR presenta un gran espectro clínico, desde la capilaritis pulmonar fulminante con HAD y falla respiratoria aguda, hasta formas más sutiles de enfermedad sólo detectables mediante lavado bronquio-alveolar (LBA). El objetivo de este estudio es presentar la primera serie peruana de SPR asociada a agentes infecciosos. Reportamos 3 casos, dos correspondieron a lupus eritematoso sistémico y uno a vasculitis asociada a poliangeítis microscópica. El primer caso se asoció a sobreinfección por C. tropicalis; el segundo caso a A. fumigatus y C. albicans; y el tercero a infestación por A. lumbricoides. Todos los casos se presentaron en mujeres, requirieron soporte ventilatorio invasivo y hemodiálisis, y dos resultaron letales. Concluimos que, el SPR es una condición clínica grave comúnmente asociada a sobreinfecciones o infestaciones, y que conlleva una elevada morbilidad y mortalidad. Puesto que no existen características clínicas específicas, resulta crucial tener un alto índice de sospecha. Las investigaciones pertinentes­pruebas inmunológicas, imagenológicas, y biopsia cutánea, renal y/o pulmonar­para precisar la etiología deben realizarse sin demora ya que el tratamiento precoz puede cambiar el pronóstico de estos pacientes(AU)

Pulmonary-renal syndrome (PRS) or reno-pulmonary syndrome is the combination of acute rapidly progressive glomerulonephritis (RPGNARP) and autoimmune diffuse alveolar hemorrhage (DAH). RPS was initially described by Goodpasture in the context of anti-glomerular basement membrane (GBM) syndrome. Currently, ANCA-associated vasculitides (AAV) explain 60% (range 56­77.5%) of cases, Goodpasture syndrome 15% (12.5­17.5%), and 10% of cases are due to other causes. PRS presents a wide clinical spectrum, from fulminant pulmonary capillaritis with ADH and acute respiratory failure, to subtler forms of disease that can only be detected by bronchoalveolar lavage (BAL). The objective of this study is to present the first Peruvian series of SPR associated with infectious agents. We report 3 cases, two corresponded to systemic lupus erythematosus and one to vasculitis associated with microscopic polyangiitis. The first case was associated with superinfection by C. tropicalis; the second case to A. fumigatus and C. albicans; and the third to infestation by A. lumbricoides. All cases occurred in women, required invasive ventilatory support and haemodialysis, and two were fatal. We conclude that SPR is a serious clinical condition commonly associated with superinfections or infestations, and that it carries high morbidity and mortality. Since there are no specific clinical features, a high index of suspicion is crucial. Relevant investigations­immunological tests, imaging tests, and skin, kidney, and/or lung biopsies­to specify the etiology should be carried out without delay, since early treatment can change the prognosis of these patients(AU)

IgA vasculitis (Henoch-Schönlein purpura) nephritis and psoriasis in a child: is there a relationship? / Vasculite por IgA (púrpura de Henoch-Schönlein), nefrite e psoríase em uma criança: existe relação?

Abstract Background Psoriasis is a chronic immune-mediated disorder that primarily affects the skin in both adults and children but can also have systemic involvement, particularly with arthritis and kidney injury. IgA nephropathy is the most frequent kidney disorder associated with psoriasis. Approximately one third of all cases of psoriasis begin in childhood, but association between psoriasis and renal disorders has scarcely been reported in pediatric patients. Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA deposits in the vessel walls of affected organs and in the mesangium of the kidney. HSP nephritis histopathology is identical to IgA nephropathy. Case report A 6-year-old boy with recent onset of psoriasis developed HSP with kidney involvement, clinically manifested by nephrotic-range proteinuria and hematuria. Kidney biopsy revealed fibrocellular glomerular crescents and mesangial IgA deposits compatible with IgA nephropathy. Treatment with systemic corticosteroids led to the control of hematuria, but as nephrotic-range proteinuria persisted, cyclophosphamide was added, leading to a gradual decrease in proteinuria. Conclusions We propose an underlying common mechanism in the pathogenesis of both HSP and psoriasis, involving a dysregulation of the IgA-mediated immune response, which could predispose to both entities as well as to kidney damage and IgA nephropathy in these patients.

Resumo Histórico A psoríase é uma doença crônica imunomediada que afeta principalmente a pele tanto em adultos quanto em crianças, mas também pode ter envolvimento sistêmico, particularmente com artrite e lesão renal. A nefropatia por IgA é o distúrbio renal mais frequentemente associado à psoríase. Aproximadamente um terço de todos os casos de psoríase começam na infância, mas a associação entre psoríase e distúrbios renais tem sido pouco relatada em pacientes pediátricos. A Púrpura de Henoch-Schönlein (PHS) é uma vasculite sistêmica caracterizada por depósitos de IgA nas paredes dos vasos de órgãos afetados e no mesângio do rim. A histopatologia da nefrite da PHS é idêntica à da nefropatia por IgA. Relato de caso Um menino de 6 anos de idade com início recente de psoríase desenvolveu PHS com envolvimento renal, clinicamente manifestado por proteinúria nefrótica e hematúria. A biópsia renal revelou crescentes fibrocelulares glomerulares e depósitos mesangiais de IgA compatíveis com a nefropatia por IgA. O tratamento com corticosteróides sistêmicos levou ao controle da hematúria, mas como a proteinúria nefrótica persistiu, a ciclofosfamida foi adicionada, levando a uma diminuição gradual da proteinúria. Conclusões Propomos um mecanismo comum subjacente na patogênese tanto da PHS quanto da psoríase, envolvendo uma desregulação da resposta imune mediada por IgA, que poderia predispor a ambas as entidades, bem como a danos renais e nefropatia por IgA nesses pacientes.

Rapidly progressive glomerulonephritis and acute kidney injury associated with cocaine use - Case report / Glomerulonefrite rapidamente progressiva e lesão renal aguda associada ao uso de cocaína - Relato de caso

ABSTRACT A wide spectrum of renal complications can occur with acute and chronic use of cocaine. Most cases are related to rhabdomyolysis, but other mechanisms are malignant hypertension, renal ischemia, and rapidly progressive glomerulonephritis (RPGN) associated-ANCA vasculitis. In recent years, the use of cocaine adulterated with levamisole has been associated with ANCA vasculitis and pauci-immune RPGN. RPGN is clinically manifested as a nephritic syndrome with a rapid and progressive decline in renal function, and its histopathological finding is the presence of crescents in more than 50% of the glomeruli. We report a case of a 38-year-old man chronic user of cocaine, alcohol, and cigarettes who had red urine, oliguria, swollen legs and eyelids, as well as the uremic symptoms anorexia, emesis, and mental confusion. He was admitted with acute kidney injury and performed six hemodialysis sessions during the first 16 days of hospitalization and then was transferred to a tertiary hospital for diagnostic investigation. Tests of ANF (antinuclear factor), ANCA, anti-DNA, serology for hepatitis B, C, and HIV virus were negative. A renal percutaneous biopsy revealed crescentic glomerulonephritis with mild tubular atrophy. The patient underwent pulse therapy with methylprednisolone (for 3 days) and cyclophosphamide. Then he maintained daily prednisone and monthly intravenous cyclophosphamide and evolved with progressive improvement of renal function.

RESUMO Um amplo espectro de complicações renais pode ocorrer com o uso agudo e crônico de cocaína. A maioria dos casos está relacionada à rabdomiólise, mas outros mecanismos são hipertensão maligna, isquemia renal e glomerulonefrite rapidamente progressiva (GNRP) associada à vasculite por ANCA. Nos últimos anos, o uso de cocaína adulterada com levamisol tem sido associado à vasculite por ANCA e GNRP pauci-imune. A GNRP se manifesta clinicamente como uma síndrome nefrítica, com um declínio rápido e progressivo da função renal, e seu achado histopatológico é a presença de crescentes em mais de 50% dos glomérulos. Relatamos um caso de um homem de 38 anos, usuário crônico de cocaína, álcool e cigarros que apresentava urina vermelha, oligúria, pernas e pálpebras inchadas, além dos sintomas urêmicos, anorexia, êmese e confusão mental. Foi internado com lesão renal aguda e realizou seis sessões de hemodiálise durante os primeiros 16 dias de internação, e depois foi transferido para um hospital terciário para investigação diagnóstica. Os testes de ANF (fator antinuclear), ANCA, anti-DNA, sorologia para vírus da hepatite B, C e HIV foram negativos. Uma biópsia percutânea renal revelou glomerulonefrite crescente, com leve atrofia tubular. O paciente foi submetido à pulsoterapia com metilprednisolona (por 3 dias) e ciclofosfamida. Em seguida, ele manteve a prednisona diária e a ciclofosfamida intravenosa mensal e evoluiu com melhora progressiva da função renal.

Primary Anetoderma and Acquired Cutis Laxa associated with Glomerulonephritis in a 37-year-old Filipino male: A case report

@#A 37-year-old Filipino man presented with a 9-month history of sagging skin progressing cephalocaudally from the chin and neck to the axillae, side of the trunk, and pelvic area. This was followed by a 2-month history of increasing serum creatinine levels associated with periorbital and bipedal edema, generalized weakness, decreased appetite, vomiting, and headache. Subsequently, skin-colored, non-tender sac-like plaques appeared on the abdomen, inguinal, and intergluteal areas. Histopathology of the latter lesions showed increased spaces between collagen bundles in the dermis. Staining with Verhoeff-van Gieson revealed focal sparse elastic fibers in the papillary dermis compared to that of the reticular dermis consistent with anetoderma. Further work-up revealed normal ANA titer and low serum C3. Kidney biopsy showed IgG deposition in the tubular basement membrane and trace C3 deposition in the glomerular mesangium, giving a diagnosis of rapid progressive glomerulonephritis. On subsequent follow-up, the sac-like plaques became lax and presented as generalized wrinkling of the skin, raising the question whether cutis laxa and anetoderma are occurring in a spectrum instead as distinct entities. Based on the current review of literature, this is the first reported case of primary anetoderma co-occurring with cutis laxa in a patient with glomerulonephritis. Deposition of immunoglobulins along the elastic fibers could have activated the complement system, mediating the destruction of the elastic fibers, resulting to cutis laxa and anetoderma. This case also considers the possibility of anetoderma and type I acquired cutis laxa occurring either in a spectrum or as distinct diseases in a single patient. Further investigations may identify an ultrastructural pattern that can help differentiate the two entities.

Inflammation and kidney involvement in human viral diseases caused by SARS-CoV-2, HIV, HCV and HBV

Inflammation is closely related to renal diseases. This is particularly true for renal diseases caused by infections as in viral diseases. In this review, we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS-CoV-2, human immunodeficiency (HIV), hepatitis C (HCV), and hepatitis B (HBV) infections. The pathophysiology of renal involvement in COVID-19 is complex, but kidney damage is frequent, and the prognosis is worse when it happens. Virus-like particles were demonstrated mostly in renal tubular epithelial cells and podocytes, which suggest that SARS-CoV-2 directly affects the kidneys. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor, which is found in endothelial cells, to infect the human host cells. Critical patients with SARS-CoV-2-associated acute kidney injury (AKI) show an increase in inflammatory cytokines (IL-1β, IL-8, IFN-γ, TNF-α), known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation, increased vascular permeability, volume depletion, thromboembolic events in microvasculature and persistent local inflammation. Besides AKI, SARS-CoV-2 can also cause glomerular disease, as other viral infections such as in HIV, HBV and HCV. HIV-infected patients present chronic inflammation that can lead to a number of renal diseases. Proinflammatory cytokines and TNF-induced apoptosis are some of the underlying mechanisms that may explain the virus-induced renal diseases that are here reviewed.(AU)

Glomerulonefritis rápidamente progresiva mediada por inmunocomplejos (tipo II). Revisión de la literatura / Immune complex-mediated rapidly progressive glomerulonephritis (type II). Literature review

La glomerulonefritis rápidamente progresiva mediada por complejos inmunes (GMNRP II) es un síndrome clínico caracterizado por el rápido deterioro de la función renal asociado a hematuria, edemas y oliguria. Histológicamente se manifiesta como una glomerulonefritis crescéntica, con la presencia de depósitos granulares en la inmunofluorescencia. Aunque es una enfermedad rara, es grave y puede evolucionar a una enfermedad renal crónica, por lo cual es fundamental su identificación temprana. A continuación, se presenta una revisión sobre este tipo de glomerulonefritis, con énfasis en su etiología y en las opciones terapéuticas existentes en la actualidad

Rapidly progressive immune complex-mediated glomerulonephritis (RPGNMN II) is a clinical syndrome characterized by severe deterioration of renal function associated with hematuria, edema, and oliguria. It is histologically characterized as a crescentic glomerulonephritis, with the presence of granular deposits on immunofluorescence. Although it is a rare condition, it is a potentially serious disease that may progress to chronic renal disease, therefore its early identification is essential. Here we present a review of this form of glomerulonephritis, with emphasis on its etiology and the currently available therapeutic options

Granulomatosis Con Poliangeítis Y Compromiso En Fosa Posterior. Reporte De Un Caso / Granulomatosis With Polyangeitis In Posterior Fosa. Report of a Case

Resumen La Granulomatosis con Poliangeitis, también conocida como granulomatosis de Wegner presenta una incidencia de 5-10 casos por millón de habitantes y solo el 2-11% de los casos presentan manifestaciones en el sistema nervioso central. No existen unos criterios diagnósticos estandarizados, sin embargo, la sospecha clínica, la serología positiva para ANCA, la evidencia histológica de vasculitis necrotizante, la glomerulonefritis necrotizante o la inflamación granulomatosa de órganos como piel, pulmón o riñón, pueden hacer pensar en dicha patología. La neurocirugía es una opción tanto diagnostica como terapéutica y debería realizarse en aquellos casos en que las lesiones se encuentren en zonas accesibles y tengan bajo riesgo de generar comorbilidades. Presentamos el caso de una paciente femenina de 39 años con cuadro de Granulomatosis con Poliangeítis con compromiso en fosa posterior a quién se le realiza un abordaje occipitocervical derecho. Posterior al manejo quirúrgico presenta infección meningea. Adicionalmente, realizamos una revisión de la literatura sobre dicha patología.

Granulomatosis with Poliangeitis or Wegner's granulomatosis has an incidence of 5-10 cases per million of habitants and only 2-11% of cases present manifestations in the central nervous system. There are no standardized diagnostic criteria, however, clinical suspicion, positive serology for ANCA 'S, histological evidence of necrotizing vasculitis, necrotizing glomerulonephritis or granulomatous inflammation of organs such as skin, lung or kidney, may suggest this pathology. Neurosurgery is a diagnostic and therapeutic option and could be a possibility in those cases in which the lesions are in accessible areas and have low risk of generating comorbidities. We present the case of a 39-year-old female patient with granulomatosis and polyangiitis with involvement in the posterior fossa. After surgical management, it presents meningeal infection. Additionally, we conducted a review of the pathology.

Anca negative pauci-immune crescentic glomerulonephritis and mixed connective tissue disease: a case study / Glomerulonefrite crescêntica pauci-imune ANCA-negativa e doença mista do tecido conjuntivo: relato de um caso

Abstract One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Resumo Uma das causas mais comuns da glomerulonefrite rapidamente progressiva (GNRP) é a glomerulonefrite crescêntica (GNC) pauci-imune. Na maioria dos casos, a patologia apresenta um marcador sorológico positivo, o anticorpo anticitoplasma de neutrófilos (ANCA), mas em cerca de 10% dos pacientes não há ANCAs circulantes, perfazendo um subgrupo da patologia conhecido como GNC pauci-imune ANCA-negativa. A GNRP pode estar associada a doenças sistêmicas, mas são poucos os relatos de caso que descrevem sua associação com doença mista do tecido conjuntivo (DMTC). O presente artigo relata um caso de GNC ANCA-negativa associada a DMTC.

Nefropatía por C1q: una rara variedad de síndrome nefrótico: caso clínico / C1q nephropathy: report of one case

C1q nephropathy is a rare glomerulopathy characterized by mesangial deposition of the complement component C1q. These deposits can be isolated or associated with immunoglobulins or complement fractions, which are observed by immunofluorescence or immunohistochemical microscopy. In ultramicroscopy, dense mesangial deposits and alterations of the podocyte are observed. Clinically it presents as a nephrotic syndrome (NS) or by alterations of the urinalysis such as proteinuria and/or hematuria in children and young adults. In light microscopy, it is expressed with a morphological pattern of minimal change disease (MCD), mesangial proliferative glomerulonephritis or focal segmental glomerulosclerosis (FSGS). The NS during its evolution usually evolve in steroid resistance or steroid dependency, often requiring the association of immunosuppressants to obtain remission. We report a 14 years old male with a history of NS and its evolution under various treatments during a 12-year follow-up.

Endocarditis por bartonella asociada a glomerulonefritis y neurorretinitis / Bartonella endocarditis associated with glomerulonephritis and neuroretinitis

La endocarditis bacteriana con hemocultivo negativo constituye un dilema diagnóstico. Tanto Bartonella como Coxiella pueden causarla, con presentaciones clínicas similares que pueden simular una vasculitis sistémica no infecciosa. Sin embargo, difieren en el tipo y la duración del tratamiento, por lo que es fundamental identificar el agente etiológico. Presentamos un caso de endocarditis por Bartonella henselae asociada a glomerulonefritis y neurorretinitis, con hemocultivo negativo, anticuerpos anticitoplasma de neutrófilos y antiproteinasa 3 positivos, y serología positiva para Bartonella con reacción cruzada para Coxiella burnetti. El diagnóstico etiológico fue confirmado a posteriori mediante amplificación y secuenciación parcial del gen ribC a partir de tejido de la válvula cardíaca. El paciente recibió tratamiento antibiótico e inmunosupresor seguido de recambio valvular aórtico y presentó evolución favorable.

Blood-culture negative endocarditis is a diagnostic challenge. Both Bartonella and Coxiella can cause it with similar clinical presentations mimicking a systemic vasculitis. The identification of the etiologic agent is essential because they differ in treatment type and duration. We present a case of blood-culture negative endocarditis caused by Bartonella henselae, associated with glomerulonephritis and neuroretinitis, with negative blood culture, positive anti-neutrophil cytoplasmic and antiproteinase 3 antibodies. The serology was positive for Bartonella with cross-reactivity to Coxiella burnetti. The etiological diagnosis was achieved by polymerase chain reaction amplification and sequencing of a ribC gene fragment. The patient received antibiotic and immunosuppressive treatment followed by replacement of the aortic valve with favorable medium-term evolution.

Glomerulonefritis infecciosa y pleuroneumonía por Streptococcus pneumoniae. Caso clínico pediátrico / Infectious glomerulonephritis and pleuropneumonia due to Streptococcus pneumoniae. Pediatric clinical case

La glomerulonefritis aguda desencadenada por Streptococcus pneumoniae es una patología de baja prevalencia. Existen diversos reportes que comunican distintas cepas nefritogénicas; sin embargo, la 6C ha sido escasamente señalada como tal.Se presenta el caso de un paciente de 4 años, quien ingresó a Terapia Intensiva con pleuroneumonía por Streptococcus pneumoniae serotipo 6C y desarrolló, de modo concomitante, edemas, hipertensión arterial, hematuria, proteinuria, disminución del filtrado glomerular y del nivel de complemento C3. Se diagnosticó glomerulonefritis aguda. Su evolución fue satisfactoria en un breve plazo. Esta patología, por lo general, es de curso transitorio y benigno; sin embargo, en ocasiones, puede complicar la evolución de un paciente críticamente enfermo, por lo cual se hace necesario tenerla entre los diagnósticos diferenciales para considerar.

Acute glomerulonephritis caused by Streptococcuspneumoniaeis a low prevalence pathology. There are several reports communicating different nephritogenic serotypes, however, 6C has been scarcely indicated as such. It is presented the case of a 4-year-old patient who entered Intensive Therapy Unit with pleuropneumonia due to Streptococcuspneumoniae serotype 6C and concomitantly developed edemas, arterial hypertension, hematuria, proteinuria, decreased glomerular filtration rate and C3 complement level. Acute glomerulonephritis was diagnosed. His evolution was satisfactory in a short time. This pathology is usually of a transitory and benign course; however, sometimes it can potentially complicate the evolution of a critically ill patient, so it is necessary to have it among the differential diagnoses to consider.

Rituximab use in adult glomerulopathies and its rationale / Uso do rituximabe em glomerulopatias em adultos e justificativas

Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.

Resumo As glomerulopatias figuram entre as principais causas de doença renal terminal. Nos últimos anos, a pesquisa clínica efetuou contribuições significativas para a compreensão desse grupo de patologias. Recentemente, o rituximabe (RTX) surgiu como um tratamento razoavelmente seguro. As diretrizes do Kidney Disease: Improving Global Outcomes (KDIGO) recomendam o RTX apenas como tratamento inicial na vasculite associada ao ANCA (VAA) e em pacientes não respondedores com nefrite lúpica (NL), embora não sejam atualizadas desde 2012. Atualmente, o RTX parece ser pelo menos tão eficaz quanto outros esquemas imunossupressores na nefropatia membranosa idiopática (NMI). Na doença por lesão mínima (DLM), o medicamento pode proporcionar um período de remissão duradouro em pacientes córtico-dependentes ou com recidivas frequentes. Resultados preliminares corroboram o uso de RTX em pacientes com NL membranosa pura e glomerulonefrite membranoproliferativa (GNMP) mediada por imunoglobulina, mas não em pacientes com NL classe III/IV ou GNMP mediada por complemento. Os achados a respeito de glomeruloesclerose segmentar e focal (GESF) idiopática e doença por anticorpo antimembrana basal glomerular (anti-MBG) não são conclusivos em função do pequeno número, porte e heterogeneidade dos estudos publicados até o presente momento. Por fim, a imunossupressão com RTX não é particularmente útil na nefropatia por IgA. A presente revisão apresenta o racional da prescrição de RTX nas diferentes glomerulopatias, desfechos e segurança. Nesse sentido, foram incluídos ensaios clínicos randomizados (ECRs) realizados em adultos, sempre que possível. Pesquisas bibliográficas foram realizadas nas bases de dados do clinictrials.gov e no PubMed.