Double Positive Anti-PR3 ANCA Vasculitis and Anti-GBM Vasculitis in a Pregnant Woman: Case Report.

Analysis and Management of Rituximab Resistance in PLA2R1-Associated Membranous Nephropathy

In critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4-21.1) ng/ml) and anti-GBM disease (5.8 (3.4-7.0) ng/ml) compared to healthy controls (1.0 (0.9-1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62-1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59-3.62) ng/ml) compared to healthy controls (2.5 (1.93-3.47) ng/ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6% per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5%; p=0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p<0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.

Eculizumab and Complement Activation in Anti−glomerular Basement Membrane Disease

Pulmonary renal syndromes: A pulmonologist's view

Anti-glomerular basement membrane (anti-GBM) disease is an acute and life-threatening systemic autoimmune disorder. The coexistence of circulating anti-neutrophil cytoplasmic antibodies (ANCA) and anti-GBM disease, the so-called double-positive disease (DPD), is exceptionally rare. We report a unique case of DPD manifesting as pulmonary-renal syndrome (PRS) in a 46-year-old woman who first presented with clinical and radiological suspicion of pneumonia. Chest computed tomography scan later revealed bilateral alveolar hemorrhage. Kidney biopsy showed necrotizing crescentic (100% glomeruli) glomerulonephritis. On immunofluorescence microscopy, glomeruli were global linear positive for IgG, confirming anti-GBM disease. Double positivity was detected for circulating anti-myeloperoxidase ANCA (p-ANCA) and anti-GBM antibodies. Acute renal failure evolved rapidly. Therapeutic plasma exchange (TPE) and hemodialysis (HD) were initiated early in combination with intravenous pulse corticosteroid therapy followed by oral methylprednisolone and cyclophosphamide. Pulmonary hemorrhage resolved, but renal function could not be preserved. The patient remains HD dependent. This case report highlights that pulmonary symptomatology may be the leading clinical presentation of PRS, with initially normal renal function at DPD onset. Early recognition and diagnosis are therefore crucial to timely clinical intervention. The role of prompt kidney biopsy and initiation of TPE and HD in PRS must not be underestimated.

Ethical Considerations Regarding Pregnancy in Chronic Kidney Disease

Anti-glomerular basement membrane (anti-GBM) disease is a systemic autoimmune disorder characterized by circulating immunoglobulin (Ig) G antibodies to carboxy-terminal, noncollagenous 1 domain of type IV collagen of GBM. Patients typically present with rapidly progressive glomerulonephritis and pulmonary hemorrhage. Anti-GBM disease has been reported to coexist with pauci-immune antineutrophil cytoplasmic autoantibody-positive glomerulonephritis and membranous glomerulopathy. The presentation of anti-GBM disease with thrombotic microangiopathy (TMA) and IgA nephropathy has been rarely described. We herein report two cases of anti-GBM antibody disease, both with crescentic glomerulonephritis and peripheral linear deposits of IgG, one case with clinical and histological findings of associated TMA and other with findings of extensive mesangial IgA deposits. Both the patients were treated with corticosteroid, intravenous cyclophosphamide, and plasma exchange but had poor renal recovery. Association of anti-GBM disease with TMA or IgA nephropathy could open up new pathogenetic mechanism and may help us to prognosticate anti-GBM disease.

IntroductionAnti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life.MethodsA retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated.ResultsCreatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25–7.84); HR 3 (1.01–9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82–0.97; p < 0.001) and 0.77 (95% CI 0.56–0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%.ConclusionIn real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.

Antiglomerular basement membrane (anti-GBM) antibody disease is a rare condition causing pulmonary hemorrhage and necrotizing glomerulonephritis (pulmonary renal syndrome). We report a 30-year-old woman who presented with life-threatening pulmonary hemorrhage and an active urinary sediment, with normal glomerular filtration rate in the 13th week of pregnancy. Anti-GBM antibodies in serum were negative, but perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) were detected. A renal biopsy revealed necrotizing glomerulonephritis with linear IgG deposits along the glomerular basement membrane. A diagnosis of pulmonary renal syndrome caused by anti-GBM antibodies and p-ANCA (double-positive) was made. Plasma exchange was started but had to be changed to immunoadsorption because of an allergic reaction to fresh frozen plasma. Oral steroids were introduced. The patient also received one dose of intravenous cyclophosphamide followed by two 1-g doses of rituximab. The patient responded quickly to treatment with resolution of pulmonary hemorrhage and urinary abnormalities. The infant was delivered in the 38th week of pregnancy by caesarian section. It was small for age but otherwise completely healthy with a normal B-cell count. To our knowledge, this is the first report of a double-positive pulmonary renal syndrome in pregnancy. Presentation in mid-pregnancy allowed for the application of cyclophosphamide without causing malformations and rituximab without B-cell depletion in the infant. .

Objective To explore the effects and influential factors of plasma exchange (PE) in patients with abnormally increased myoglobin (Mb). Methods From March 2014 to December 2016, a total of 57 patients with abnormally increased Mb who underwent PE treatment at the First Hospital Affiliated to Army Medical University were selected as subjects. There were 44 male patients and 13 females; and the age of them was (50.1 ± 14.7) years old. A retrospective study was performed to collect blood routine examination and coagulation function indicators before PE treatment and after the last PE treatment, as well as serum Mb and serum creatinine (Scr) values after each PE treatment, respectively. Among them, blood routine examination indicators included white blood cell count (WBC), hemoglobin (Hb) value, platelet count and hematocrit(HCT); coagulation function indicators included activated partial thromboplastin time (APTT) and prothrombin time (PT). Paired t-test or Wilcoxon signed rank test was used to compare indicators of blood routine examination and coagulation function before and after PE treatment. Kaplan-Meier survival analysis was used to univariately analyze the factors (gender, age, disease inducement, serum Mb and Scr values before treatment) affecting the effective recovery rates of serum Mb and Scr values. This study met the requirements of the Helsinki Declaration of the World Medical Association revised in 2013. Results ① In this study, the WBC, Hb value, HCT and APPT of these 57 patients with abnormally increased Mb after PE treatment were lower than those before PE treatment, and the differences were statistically significant (t=2.291, P=0.026; t=5.033, P<0.001; t=5.079, P<0.001; Z=2.111, P=0.035). Platelet count and PT of patients decreased after treatment, but the differences were not statistically significant (Z=0.133, P=0.894; Z=1.624, P=0.104). ② In this study, there were 41 patients whose serum Mb values decreased to <1 000 μg/L after PE treatment, and the effective recovery rate of serum Mb value was 71.9% (41/57). Results of univariate analysis showed that the serum Mb and Scr values before PE treatment were the influencing factors of the effective recovery rates of serum Mb value after PE treatment (P=0.031, 0.037); and the disease inducement, serum Mb and Scr values before PE treatment were the influencing factors of effective recovery rates of Scr value after PE treatment (P=0.036, <0.001, =0.003). Conclusions PE treatment could effectively eliminate serum Mb value in patients with abnormally increased Mb and prevent renal damage. The PE treatment should be implemented as early as possible, which is able to protect renal against extended impairment at the largest extent. Key words: Plasma exchange; Myoglobin; Acute kidney injury; Creatinine; Blood purification

Non-bioartificial liver has been applied to clinic for quite a long time, but the reported efficacy has been very different. The aim of this study was to compare the efficacy and safety of hemoperfusion adsorption, plasma exchange and plasma exchange plus hemoperfusion adsorption in treatment of severe viral hepatitis. Seventy-five patients with severe viral hepatitis were treated with hemoperfusion adsorption therapy (24 cases), plasma exchange therapy (17 cases) and plasma exchange plus hemoperfusion adsorption therapy (34 cases). The data of liver function, renal function, blood routine test, prothrombin time (PT) and prothrombin activity (PTa) pre- and post-therapy were analyzed. Clinical symptoms of patients improved after treatment. The levels of aminotransferase, total bilirubin, direct bilirubin decreased significantly after 3 therapies (P<0.05 or P<0.01). PT, the level of total serum protein decreased significantly and PTa increased significantly after plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy (P<0.05 or P<0.01). The side effects were few and mild in all patients. Three therapies were effective in the treatment of severe viral hepatitis. Plasma exchange therapy and plasma exchange plus hemoperfusion adsorption therapy are better than hemoperfusion adsorption therapy.

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic necrotizing glomerulonephritis, with linear deposits of immunoglobulin G (IgG) in the GBM. Classic anti-GBM disease is clinically associated with rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Some patients have a better renal prognosis and milder symptoms than those with classic anti-GBM disease, which is termed atypical anti-GBM disease.Case presentationA 43-year-old Japanese woman was admitted to our hospital complaining of hematuria that had persisted for more than one month. Serological examination revealed negativity for anti-nuclear, anti-neutrophilic cytoplasmic, and anti-GBM antibodies. However, renal biopsy showed cellular crescents. Immunofluorescence revealed strong diffuse linear capillary loop staining for IgG. An indirect immunofluorescence antibody method was performed by applying the patient serum to normal kidney tissue to confirm the presence of autoantibodies binding to the GBM. Using this method, anti-GBM antibodies were detected. The patient was treated with high-dose steroids, cyclophosphamide, and plasma exchange. Aggressive treatment resolved proteinuria and hematuria and improved renal function.ConclusionsRenal biopsy is crucial in the diagnosis of anti-GBM disease, especially when serological tests are negative. Accurately identifying the presence of anti-GBM disease is important to initiate optimal treatment.

Pulmonary renal syndrome (PRS) is a high mortality, rare disorder presenting with diffuse alveolar hemorrhage and progressive acute glomerulonephritis. This syndrome is often caused by autoimmune entities, the most frequent being ANCA positive vasculitis and anti-GBM disease. We report a case of a 34-year-old Chilean woman, who initially presents with anemia and after a few days of inpatient management, starts with progressively worsening dyspnea, decrease in renal function and hematuria. The patient is initially diagnosed with pneumonia, but further evaluation using Thorax CT scan and renal biopsy confirms the suspicion of PRS. The case is of particular interest due to the lack of extensive bibliography on anti-GBM and ANCA negative pulmonary-renal syndrome, an uncategorized subtype of this syndrome with unknown optimal management.

BackgroundSystemic sclerosis is a chronic immune disease characterized by varying degrees of fibrosis of skin and internal organs. Microscopic polyangitis, as a subtype of ANCA associated vasculitis, mainly involves small...

BackgroundAnti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection.Case presentationThe 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome.ConclusionOur case supports the assumption of a possible association between COVID-19 and anti-GBM disease.