COVID-19, glomerulonefritis ANCA y anti-membrana basal glomerular. Caso clínico / Association of COVID-19 and glomerulonephritis with ANCA and anti-glomerular basement membrane antibodies. Report of one case

Renal involvement in COVID-19 infection is varied and worsens its outcome and prognosis. However, the association of COVID-19 infection with glomerulonephritis is exceptional. We report a 46-year-old woman with COVID-19 who had an acute kidney injury and ANCA associated glomerulonephritis two weeks after the onset of the disease. The kidney biopsy showed a crescentic glomerulo-nephritis and the presence of anti-glomerular basement membrane antibodies (GBM-Abs). She was treated with steroids and oral cyclophosphamide with good response without requiring plasmapheresis. Plasma anti GBM-Abs were negative. This case suggests that the presence of anti-GBM-Abs in the kidney, was temporally related to COVID-19 pulmonary damage. The absence of plasma antibodies is probably due to transient production and glomerular adsorption, but with unknown pathogenic role.

Recurrencia de Síndrome de Goodpasture con negativización de anticuerpos anti-membrana basal glomerular: caso clínico / Recurrence of goodpasture syndrome with negative antiglomerular basement antibodies: report of one case

Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

Establishment of rat model of anti-glomerular basement membrane nephritis induced by pCol (24-38) / 解放军医学杂志

Objective Polypeptide pCol (24-38) containing rat non-collagen region of collagen type IV alpha 3 chain [α3(IV)NC1] was used as antigen to establish the rat model of anti-glomerular basement membrane (GBM) disease, and study the possible pathogenesis of anti-GBM disease. Methods Twenty male WKY rats, 8-10 weeks old and weight 120-150g, were randomly divided into control group and anti-GBM model group (10 each). Polypeptide pCol(24-38) was used as antigen in anti-GBM model group, while pCol (38-52) was used as antigen in control group. After emulsification with complete Freund's adjuvant, rats in the both groups were immunized by subcutaneous injection at three points on the back. 24-hour urine was collected regularly every week after immunization to measure the urinary protein content. All animals were sacrificed 49 days after immunization, and serum was taken. The serum creatinine level was detected by creatine oxidase method, urea nitrogen concentration was determined by urease method, and the relative titer of serum anti-pCol (24-38) antibodies was detected by indirect ELISA. Part of kidney tissue was stained with PAS and immunohistochemically treatment in paraffin section, and the other part was frozen section after OCT embedding to detect IgG deposition in glomeruli by direct immunofluorescence method. Results The 24-hour urinary protein levels increased significantly from the 4th week in anti-GBM model group than in control group [(52.27±10.50)mg/24h vs. (4.87±0.64)mg/24h, P<0.001], and then rose gradually until the 7th week [(255.80±9.79)mg/24h vs. (5.78±0.39)mg/24h, P<0.001]. Both the serum creatinine level and urea nitrogen level increased obviously in anti-GBM model group than in control group [(145.3±22.60)μmol/L vs. (36.81±2.21)μmol/L; (26.59±5.01)mmol/L vs. (6.92±0.27)mmol/L] with statistically significant difference (P<0.001). Compared with the control group, rats in anti-GBM model group produced high levels of circulating anti-pCol (24-38) IgG antibodies [(1.59±0.18) vs. (0.09±0.01)] with statistically significant difference (P<0.05). PAS staining showed glomerular sclerosis and diffuse crescent formation in anti-GBM model group; immunohistochemistry showed macrophage infiltration in glomerular; fluorescence staining showed obvious linear deposition of IgG in glomerular basement membrane. However, in the control group, PAS staining showed no abnormal glomerular, immunohistochemistry showed no macrophage infiltration, and fluorescence staining showed no IgG deposits on the glomerular basement membrane. Conclusions The animal model of anti-GBM disease may be successfully constructed by using polypeptide pCol (24-38) as antigen to immunize WKY rats. The preparation method of the antigen is simple, and so is valuable for designing new therapeutic strategies against anti-GBM disease.

Concurrent Anti-glomerular Basement Membrane Nephritis and IgA Nephropathy

Anti–glomerular basement membrane (GBM) nephritis is characterized by circulating anti-GBM antibodies and crescentic glomerulonephritis (GN) with deposition of IgG along the GBM. In a limited number of cases, glomerular immune complexes have been identified in anti-GBM nephritis. A 38-year-old female presented azotemia, hematuria, and proteinuria without any pulmonary symptoms. A renal biopsy showed crescentic GN with linear IgG deposition along the GBM and mesangial IgA deposition. The patient was diagnosed as concurrent anti-GBM nephritis and IgA nephropathy. Therapies with pulse methylprednisolone and cyclophosphamide administration were effective. Concurrent cases of both anti-GBM nephritis and IgA nephropathy are rare among cases of anti-GBM diseases with deposition of immune complexes. This rare case of concurrent anti-GBM nephritis and IgA nephropathy with literature review is noteworthy.

Nursing care of two cases of anti-glomerular basement membrane disease / 现代临床护理

Objective To summarize the experience in nursing 2 patients with anti-glomerular basement membrane disease.Method The nursing measures such as close observation of disease condition,careful nursing of medication,nursing during the treatment of double filtrated plasmapheresis and mental care to the patients and their family members.Results After treatment,the concentration of anti-GBM antibody was declined and the level of serum creatinine was also decreased.The renal function got rccovered to a certain extent.Conclusion Such nursing points as close observation of renal and pulmonary pathgenesis,timely and accurate administration of medicine according to doctor's orders and active observation and prevention of complication from double filtrated plasmapheresis are key.

One neonate with bullae of lung whose mother diagnosed with Goodpasture's syndrome during pregnancy:case report and review of the literatures / 中华围产医学杂志

Objective To summarize the clinical features and possible impacts of Goodpasture's syndrome in pregnancy on the pulmonary and kidney of the newborn and the mothers. Methods One patient diagnosed Goodpasture's syndrome in pregnancy hospitalized in Peking Union Medical College Hospital on August 23 in 2011 delivered a neonate with bullae of lung. And literatures including 8 cases of pregnancy complicated by Goodpasture's syndrome worldwide through Medline were reviewed. Results (1) Case report:one 31-year-old women presented with acute renal failure at 30+6 weeks of gestation and delivered a male infant with birth weight 1 900 g by caesarean section at 31+1 weeks of gestation. Diagnosis was confirmed as Goodpasture's syndrome with anti-glomerular basement membrane(GBM) antibodies in serum and renal biopsy after delivery. Then she was treated with methylprednisolone, cyclophosphamide, plasmapheresis and dialysis. The neonate showed the lung bullae in the right middle lobe and bilateral intraventricular hemorrhage but renal function was transient normal with anti-GBM as 113.1 EU/ml. The baby was treated by glucocorticoid for two months and clinical symptoms were improved. Anti-GBM antibodies and chest CT showed normal. After been followed up for two years, the baby was normal. (2) Literatures review:the main manifestations of Goodpasture's syndrome in pregnancy were malignant hypertension and renal failure but respiratory symptoms were not obvious. Treated with plasmapheresis, hematodialysis and glucocorticoid maybe have good effects. Most cases had premature delivery. Neonatal anti-GBM antibodies coming from mothers could result to cerebral, renal and pulmonary injury which could be treated by glucocorticoid. Conclusions The Clinical features of pregnancy complicating the Goodpasture's syndrome are malignant hypertension and renal failure. Diagnosis was depended on positive anti-GBM antibodies and renal pathological changes and treatment were depended on plasmapheresis, hematodialysis and glucocorticoid. Neonatal cerebral, renal and pulmonary injury resulting from anti-GBM antibodies coming from mothers should be followed up, and glucocorticoid should be taken if necessary.

Effects of mycophenolate mofetil on anti-glomerular basement membrane nephritis SD rats / 重庆医学

Objective To investigate the influence of mycophenolate mofetil(MMF) on blood and urine biochemical indica‐tors as well as the expressions of IL‐1 in anti‐glomerular basement membrane(GBM ) nephritis SD rats .Methods The SD rats were randomly divided into control group ,model group and MMF group .And then the models of SD rat anti‐GBM nephritis were estab‐lished by injecting rabbit anti‐SD rat GBM serum antibodies .The urinary protein and blood parameters were detected initially ,1st , 2nd ,3rd and 4th weeks after administration respectively .The expressions of IL‐1 and TGF‐β1 were detected by Elisa Kit and the re‐nal pathological changes were observed by HE and PAS staining .Results After treatment for 4 weeks by MMF ,the 24 h UP ,BUN and SCr levels were lower in MMF group than those of the model group(P<0 .05) .And the expressions of IL‐1 and TGF‐β1 were decreased in MMF group .The results of HE and PAS staining showed that in model group rats ,glomerular tuft morphology was destroyed and inflammatory cell infiltration was observed in the glomeruli .Some glomeruli had cellular crescent formation .Infiltra‐tion of inflammatory cells was also observed in the interstitium .MMF clearly improved these pathological changes overall ,with im‐provements noted in both glomerular and tubular degeneration as well as in the infiltration of inflammatory cells .Conclusion MMF shows certain renal protective effect on anti‐GBM nephritis SD rats .

Laboratory tests in autoimmune renal diseases:an update / 中华检验医学杂志

Autoimmune diseases are characterized by the presence of various autoantibodies and may cause injuries to multiple organs,with kidney as the most common and important organ involved.Autoantibodies are of great importance in the diagnosis,treatment and prognosis of autoimmune renal diseases.Lupus nephritis,anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and antiglomerular basement membrane (GBM) disease are the most common autoimmune renal diseases.Anti-C1q antibody,ANCA and anti-GBM antibody play important roles in those diseases,respectively.Appropriate and steady detecting methods are crucial to clinicians,and the results should also be interpreted with great cautions.

Association of anti-glomerular basement membrane antibody disease with dermatomyositis and psoriasis: case report / Associação de doença do anticorpo anti-membrana basal glomerular com dermatomiosite e psoríase: relato de caso

CONTEXT: Anti-glomerular basement membrane (anti-GBM) antibody syndrome is characterized by deposition of anti-GBM antibodies on affected tissues, associated with glomerulonephritis and/or pulmonary involvement. This syndrome has been described in association with other autoimmune disorders, but as far as we know, it has not been described in association with dermatomyositis and psoriasis. CASE REPORT: A 51-year-old man with a history of dermatomyositis and vulgar psoriasis presented with a condition of sensitive-motor polyneuropathy of the hands and feet, weight loss of 4 kg, malaise and fever. On admission, he had been making chronic use of cyclosporin and antihypertensive drugs for three months because of mild arterial hypertension. Laboratory tests showed anemia and leukocytosis, elevated serum urea and creatinine and urine presenting proteinuria, hematuria, leukocyturia and granular casts. The 24-hour proteinuria was 2.3 g. Renal biopsy showed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG) deposits on the glomerular basement membrane by means of direct immunofluorescence, which were suggestive of anti-GBM antibodies. The patient was then treated initially with methylprednisolone and with monthly cyclophosphamide in the form of pulse therapy.

CONTEXTO: A síndrome do anticorpo anti-membrana basal glomerular (anti-MBG) é caracterizada pela deposição de anticorpos anti-MBG em tecidos afetados, associada à glomerulonefrite e/ou ao envolvimento pulmonar. Essa síndrome já foi descrita em associação a outras doenças autoimunes, mas até onde conhecemos, não há relatos de sua associação com dermatomiosite e psoríase. RELATO DE CASO: Um homem de 51 anos com antecedentes de dermatomiosite e psoríase vulgar apresentou quadro de polineuropatia sensitivo-motora de mãos e pés, perda de 4 kg, adinamia e febre. À admissão estava em uso crônico de ciclosporina e de anti-hipertensivos há três meses devido a hipertensão arterial leve. Exames laboratoriais mostraram anemia e leucocitose, creatinina e ureia séricas elevadas e urina com proteinúria, hematúria, leucocitúria e cilindros granulosos. A proteinúria de 24 horas foi de 2,3 g. A biópsia renal revelou uma glomerulonefrite crescêntica necrotizante com depósitos lineares de imunoglobulina G (IgG) na MBG à imunofluorescência, sugestivos de anticorpos anti-MBG. O paciente foi então tratado inicialmente com metilprednisolona e com ciclofosfamida mensalmente na forma de pulsoterapia.

Experimental study of application of anti-glomerular basement membrane antibodies neutralizing monoclonal antibody on anti-glomerular basement membrane nephritis rats / 中华肾脏病杂志

Objective To observe the effect of neutralizing monoclonal antibodies to antiglomerular basement membrane (GBM) antibody on anti-GBM nephritis rats. Methods Wistar rats were randomly divided into five groups: control group Ⅰ was a negative control and was injected with healthy human IgG via the caudal vein. Control group Ⅱ was injected with neutralizing monoclonal antibodies to anti-GBM antibody only. Anti- GBM nephritis group was injected with human anti-GBM antibody via the caudal vein only. Intervention group Ⅰ was injected with human anti-GBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 7. Intervention group Ⅱ was injected with human antiGBM antibody via the caudal vein and then with neutralizing monoclonal antibodies to anti-GBM antibody at day 14. The blood, urine and kidney tissue were collected at day 7, 14, 21 for analysis of 24-hour urinary protein, BUN, Ser and histological study. Results At day 21, there were significant decreases in intervention group Ⅰ compared with anti-GBM nephritis group in 24-hour proteinuria [(16.62±5.53) g], BUN[(11.53±2.26) mmol/L] and Scr [(102.46±16.86) μmol/L] (P＜0.05), and also in intervention group Ⅱ as compared to anti-GBM nephritis group, but no significant difference was found (P＞0.05) . There was obvious decrease of renal cell proliferation,crescent formation and deposition of immune complexes in intervention group Ⅰ and intervention group Ⅱ compared with anti-GBM nephritis group, while such improvement in intervention group Ⅰ was more significant. There was no significant change in control group Ⅰ and control group Ⅱ.Conclusion The early application of neutralizing monoclonal antibodies to anti-GBM antibodies can effectively improve the kidney lesions of anti-GBM nephritis rats.

The Role of MCP 1 and IL 6 on the Progress of Crescentic Glomerulonephritis / 대한신장학회지

PURPOSE: Growing data on the relationship between cytokine expression and the progression of renal diseases make these cytokines potential targets for therapeutic interventions. Weexamined the helper T1-cell- and macrophage-associated cytokines in anti-glomerular basement membrane (GBM) antibody-induced nephritis in mice and their temporal relationships with renal tissue fibrosis. METHODS: Kidneys were harvested on days 1, 3, 7, 11, and 16 after glomerulonephritis was induced with anti-GBM antibody. The progression of renal fibrosis was serially monitored to quantitate the accumulation of cortical extracellular matrix, and various cytokines were measured simultaneously. RESULTS: A single injection of anti-GBM antibody successfully produced severe crescentic glomerulonephritis. Proteinuria increased abruptly and both mesangial matrix expansion and interstitial fibrosis progressed rapidly. Cortical fibronectin and type III collagen increased continuously, reaching a peak on day 7, and the deposition of type III collagen followed the same pattern, in parallel with that of urinary transforming growth factor 1 (TGF-1) expression. Serial cytokine measurements revealed a sustained increase in interleukin (IL) 6 and monocyte chemoattractant protein 1 (MCP1) from day 3, but neither IL12, IL18, nor interferon changed significantly. Real-time polymerase chain reaction confirmed these features at the transcription level. CONCLUSION: MCP1 and IL6 correlated with the progression of renal fibrosis, with no increase in Th1- inducing cytokines. This confirms MCP1 and IL6 as attractive therapeutic targets for renal fibrosis in crescentic glomerulonephritis.

A Case of Anti-Glomerular Basement Membrane Disease Improved by Early Plasmapheresis and Immunosuppression Therapy / 대한신장학회지

Anti-glomerular basement membrane disease is a rare autoimmune disease characterized by rapidly progressive renal failure and/or pulmonary hemorrhage. The presence of severe crescentic glomerular inflammation with linear deposition of immunoglobulin G along the glomerular basement membrane is pathognomonic. Because renal function is rapidly and often irretrievably destroyed, many patients require hemodialysis all through their lifetime. We report a case of 33 year(s)-old man who was diagnosed as anti-glomerular basement membrane disease without pulmonary hemorrhage. The patient was treated with pulse methylprednisolone and plasmapheresis followed by oral corticosteroid and cyclophosphamide. His renal function was successfully recovered with early diagnosis and aggressive treatment.

A Case of Anti-glomerular Basement Membrane Disease which Presented with Fever of Unknown Origin / 대한신장학회잡지

Anti-glomerular basement membrane disease is an autoimmune disorder characterized progressive renal failure and/or lung hemorrhage. Most of patients present with acute renal failure or acute nephritic feature such as hematuria, proteinuria, and leukocyturia in urinalysis. A part of patients present with pulmonary hemorrhage, anemia, tachypnea, and cyanosis. It is accompanied with transient fever and myalgia but fever of unknown origin (FUO) is very rare condition. We report the atypical case of anti-glomerular basement membrane mediated rapidly progressive glomerulonephritis which presented with FUO and shock after methylprednisolone pulse therapy.

The Role of MIB-1 Expression and Apoptosis in Experimental Crescentic Glomerulonephritis

It has been postulated that programmed cell death via apoptosis may be critical for remodelling of glomeruli after inflammatory injury. To understand the regulatory mechanism of apoptosis in experimental crescentic glomerulonephritis (CGN), we examined the MIB-1 score (proliferation index, PI) and apoptotic index during the progression of experimental CGN to end-stage renal failure. CGN was induced in New Zealand White rabbits by administration of guinea pig anti-GBM IgG after sensitization with guinea pig IgG and their kidneys were analyzed for the development of crescents through sequential renal biopsies. Serum creatinine levels progressively increased in a time course until day 45. The PI in glomeruli, tubular epithelial cells, and interstitium progressively increased during the progression of experimental CGN. The mean numbers of MIB-1 positive intraglomerular nuclei (PI) were significantly correlated with degrees of crescent formation and the numbers of apoptotic cells in the glomeruli, tubules, and interstitium. Significant apoptosis was present from day 1 (15.8 10.16 cells/glomerular cross section) and increased in number with the proliferative lesions as glomerular inflammation continued. Moreover, apoptosis increased during the resolution of the glomerular inflammation, and many apoptotic cells were present in the sclerotic lesions in day 17 (18.6 12.99 cells/glomerular cross section). As glomerular inflammation subsided, cellular crescents progressed to fibrous crescents with a reduction of cellularity by day 45. On day 45, the glomerular PI and the numbers of apoptotic cells were markedly decreased. The correlations found in CGN between the creatinine level and the percentage of crescents, between the percentage of crescent and PI, and between the PI and number of apoptotic cells support the hypothesis that there is a change in the glomerular and tubulo-interstitial apoptosis under pathologic conditions. These findings indicate that apoptosis plays an essential role in the resolution of intra- and extraglomerular inflammation and in the elimination of glomerular cells within the sclerotic regions for progressive CGN. The regulation of the apoptotic phenomenon and increased PI during CGN may be important in the progression of glomerular inflammation and the development of pathologic glomerular sclerosis.