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1.
Rinsho Ketsueki ; 62(5): 430-434, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34108326

RESUMO

In this article, I mainly review the molecular targeted therapy for thrombotic thrombocytopenic purpura (TTP). TTP is one of thrombotic microangiopathies (TMA), which demonstrate hemolytic anemia with red blood cell destruction and thrombocytopenia. Another TTP, hemolytic uremic anemia (HUS) reveals bloody stood and acute kidney failure. As it is difficult to correctly diagnose TTP based on clinical symptoms alone, a confirmation of whether ADAMTS13 activity is lower than 10% is required. In the past few years, TTP was designated as an intractable disease by law, and the clinical application of ADAMTS13 test and rituximab became labeled in Japan. Currently, we are expecting that recombinant ADAMTS13 and caplacizumab for immune TTP will be applied.


Assuntos
Anemia Hemolítica , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Proteína ADAMTS13 , Humanos , Japão , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Rituximab/uso terapêutico
2.
Medicine (Baltimore) ; 100(20): e25986, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011089

RESUMO

ABSTRACT: Thrombotic microangiopathy (TMA) syndromes are extraordinarily diverse in clinical presentations and etiologies. However, there are still a limited number of large cohort studies focusing on the underlying causes, outcomes, and response to plasmapheresis.A retrospective study was designed to understand trigger etiologies, organ dysfunctions, clinical outcomes, and efficacy of plasmapheresis in patients with TMA. The whole population of Taiwan was set up into 2 cohorts: 875 patients with TMA in the 2006 cohort (2006-2010) and 1352 patients with TMA in the 2011 cohort (2011-2015). One hundred ninety-five patients in the 2006 cohort and 272 patients in the 2011 cohort were under plasmapheresis treatment.The common underlying etiologies were pregnancy, followed by systemic lupus erythematosus, rheumatoid arthritis, transplantation and drugs, which were significantly higher than the control group. Stroke, seizure, arterial thrombosis, vascular stenosis, hypertension, myocardial infarction, and pancreatitis were the main clinical signs and extra-renal involvements. In the multivariate regression analysis, stroke, arterial thrombosis, peripheral arterial disease, and uremia were significantly higher compared with the control group. The mortality rate in TMA under plasmapheresis was significantly higher than all TMA cases (39.33% vs 15.39% in the 2006 cohort and 39.27% vs 15.06% in the 2011 cohort).This study indicated the spectrum of underlying causes, extra-renal characteristics, and the response to plasmapheresis of patients with TMA in Taiwan. Of note, the poor clinical outcomes of plasmapheresis in patients with TMA might highlight the masked underlying etiology or worse disease condition that should be noticed.


Assuntos
Plasmaferese/estatística & dados numéricos , Microangiopatias Trombóticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Feminino , Glucocorticoides , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/mortalidade , Microangiopatias Trombóticas/terapia , Resultado do Tratamento , Adulto Jovem
3.
Medicina (Kaunas) ; 57(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799854

RESUMO

Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.


Assuntos
Injúria Renal Aguda/patologia , Glomerulonefrite/patologia , Rim/patologia , Microangiopatias Trombóticas/patologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/imunologia , Imunidade Adaptativa/imunologia , Arteriosclerose/imunologia , Arteriosclerose/patologia , /imunologia , Citocinas/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/patologia , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Imunidade Inata/imunologia , Infarto/imunologia , Infarto/patologia , Rim/irrigação sanguínea , Rim/imunologia , Necrose do Córtex Renal/imunologia , Necrose do Córtex Renal/patologia , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Nefrose Lipoide/imunologia , Nefrose Lipoide/patologia , Rabdomiólise , Trombofilia/sangue , Microangiopatias Trombóticas/imunologia
4.
Clin Immunol ; 226: 108726, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33845193

RESUMO

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.


Assuntos
Proteína ADAMTS13/genética , Complemento C3/genética , Predisposição Genética para Doença/genética , Trombomodulina/genética , Idoso , Algoritmos , Ativação do Complemento , Fator H do Complemento/genética , Cuidados Críticos , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Microangiopatias Trombóticas/genética
6.
Int J Mol Sci ; 22(8)2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33919576

RESUMO

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.


Assuntos
Síndrome Antifosfolipídica/imunologia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Nefropatias/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Microangiopatias Trombóticas/imunologia , Animais , Síndrome Antifosfolipídica/metabolismo , Humanos , Nefropatias/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Microangiopatias Trombóticas/metabolismo
7.
Blood Adv ; 5(8): 2106-2114, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33877298

RESUMO

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P < .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/prevenção & controle
8.
Cochrane Database Syst Rev ; 3: CD012862, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33783815

RESUMO

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs. SELECTION CRITERIA: All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/mortalidade , Viés , Inativadores do Complemento/efeitos adversos , Taxa de Filtração Glomerular , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Qualidade de Vida , Microangiopatias Trombóticas/tratamento farmacológico
9.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653851

RESUMO

Ramucirumab-induced renal dysfunction is rarely reported. The pathology of ramucirumab-associated nephropathy in past reports primarily shows thrombotic microangiopathy (TMA) lesions but podocytopathy is not yet known. We report a case of kidney injury induced by ramucirumab in a 71-year-old man with cecal cancer. He was referred to our department for increasing serum creatinine (Cr) levels from 1.08 mg/dL to 2.56 mg/dL after changing anticancer drugs from bevacizumab to ramucirumab. He showed nephrotic-range proteinuria (12.1 g/gCr). A renal biopsy revealed endothelial cell injuries, such as TMA and podocytopathy with epithelial cell hyperplasia, which looked like a crescent. After discontinuing ramucirumab, his renal function and proteinuria improved, as seen by his Cr levels and proteinuria which decreased to 1.74 mg/dL and 1.21 g/gCr, respectively, in 3 months. Unlike previous reports, we found that ramucirumab caused podocyte injuries.


Assuntos
Insuficiência Renal , Microangiopatias Trombóticas , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Masculino , Proteinúria/induzido quimicamente , Microangiopatias Trombóticas/induzido quimicamente
10.
Eur J Obstet Gynecol Reprod Biol ; 260: 29-36, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33713886

RESUMO

Therapeutic plasma exchange (TPE) is indicated as a treatment for a wide array of diseases, extensively addressed in the Guidelines of the American Society for Apheresis. In pregnancy, TPE is an uncommon event and application is largely based on extrapolation of efficacy and safety in a non-pregnant population. This review intends to describe the currently available experience of TPE in pregnancy to help clinicians recognise indications during pregnancy and to support current guideline recommendations with literature-based experiences. In order to identify the clinical indications for which TPE is applied in pregnant women, we performed a literature search including studies till November 2019, without a start date restriction. Data extraction included medical indication for TPE and safety of TPE in pregnant women. 279 studies were included for analysis. Nowadays, TPE is predominantly applied for thrombotic microangiopathies, lipid disorders and a variety of autoimmune diseases. The application of TPE during pregnancy remains largely empiric and relies on individual case reports in the absence of high-quality studies and definitive evidence-based guidelines. Safety profile of TPE during pregnancy appears to be comparable to application of TPE in non-pregnant patients. In conclusion, based on the limited evidence that we found in literature with a high risk of publication bias, TPE procedures can be used safely during pregnancy with the appropriate preparation and experience of a multidisciplinary team.


Assuntos
Doenças Autoimunes , Remoção de Componentes Sanguíneos , Microangiopatias Trombóticas , Doenças Autoimunes/terapia , Feminino , Humanos , Troca Plasmática , Gravidez , Estudos Retrospectivos
11.
BMC Infect Dis ; 21(1): 137, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33526010

RESUMO

BACKGROUND: The use of complement inhibition is well established for complement mediated thrombotic microangiopathy, but its role in secondary forms of thrombotic microangiopathy is debated. We here present a case of thrombotic microangiopathy triggered by Capnocytophaga canimorsus, illustrating the diagnostic difficulties in discriminating between different thrombotic microangiopathies, and the dilemmas regarding how to treat this disease entity. CASE PRESENTATION: A previously healthy 56-year-old woman presented with fever and confusion. She was diagnosed with sepsis from Capnocytophaga canimorsus and thrombotic microangiopathy. Marked activation of both T-cells, endothelium and complement were documented. She was successfully treated with antimicrobial therapy, the complement inhibitor eculizumab and splenectomy. After several weeks, a heterozygote variant in complement factor B was localized, potentially implying the diagnosis of a complement mediated TMA over an isolated infection related TMA. CONCLUSIONS: We discuss the possible interactions between complement activation and other findings in severe infection and argue that complement inhibition proved beneficial to this patient's rapid recovery.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Capnocytophaga/patogenicidade , Ativação do Complemento , Inativadores do Complemento/uso terapêutico , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/tratamento farmacológico , Feminino , Infecções por Bactérias Gram-Negativas , Humanos , Pessoa de Meia-Idade , Noruega/epidemiologia , Sepse/etiologia
12.
Br J Haematol ; 193(1): 43-51, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538335
13.
BMJ Case Rep ; 14(2)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637496

RESUMO

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Humanos , Masculino , Oligopeptídeos/efeitos adversos
14.
Blood Adv ; 5(1): 1-11, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33570619

RESUMO

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study has shown that the incidence of TA-TMA is much higher than prior retrospective studies that did not systematically screen. These data have not been replicated in a multicenter study. Our objective was to determine the incidence and risk factors for TA-TMA and compare outcomes of pediatric HSCT patients with and without TA-TMA. Patients were prospectively screened for TA-TMA at participating centers using a simple to implement and inexpensive strategy from the start of the preparative regimen through day +100. TA-TMA was diagnosed if ≥4 of 7 laboratory/clinical markers diagnostic for TA-TMA were present concurrently or if tissue histology showed TA-TMA. A total of 614 patients (359 males; 58%) received prospective TA-TMA screening at 13 pediatric centers. TA-TMA was diagnosed in 98 patients (16%) at a median of 22 days (interquartile range, 14-44) posttransplant. Patients with TA-TMA had significantly increased bloodstream infections (38% [37/98] vs 21% [107/51], P ≤ .001), mean total hospitalization days (68; 95% confidence interval [CI], 63-74 vs 43; 95% CI, 41-45; P ≤ .001), and number of days spent in the intensive care unit (10.1; 95% CI, 6.4-14; vs 1.6; 95% CI, 1.1-2.2; P ≤ .001) in the first 100 days after HSCT compared with patients without TA-TMA. Overall survival was significantly higher in patients without TA-TMA (93%; 490/516) compared with patients with TA-TMA (78%; 76/98) (P ≤ .001). These data support the need for systematic screening for TA-TMA and demonstrate the feasibility and efficacy of an easy to implement strategy to do so.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia
15.
Clin Rheumatol ; 40(7): 2735-2743, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33543375

RESUMO

OBJECTIVES: Non-immune complex (IC)-mediated renal thrombotic microangiopathy (TMA) has been reported in patients with systemic lupus erythematosus (SLE), but most studies included patients with both renal TMA and IC-mediated lupus nephritis (LN). In this study, the clinicopathological features and outcomes of renal injury characterised by only renal TMA were retrospectively analyzed. METHODS: Patients with glomerular and/or vascular TMA in the absence of subendothelial or epithelial immune deposits were screened from 2,332 biopsied of SLE patients. The TMA lesions were divided into glomerular, vascular or both. Acute tubular-interstitial injury was semi-quantitatively analyzed. The podocyte foot process effacement (FPE) was measured by electronic microscopy. RESULTS: Two hundred fifty-seven (11.0%) renal biopsies revealed TMA, among which 237 biopsies showed TMA coexisting with LN, and 20 (0.9%) biopsies had only renal TMA without or with only mesangial immune deposits. All patients manifested with acute kidney injury and haematological disorders. Among them, 11 (55%) required renal replacement therapy, 12 (60%) had nephrotic syndrome and 13 (65.0%) showed microvascular haemolytic anaemia with thrombocytopenia. Seventeen (85%) biopsies revealed both glomerular TMA and vascular TMA, two had only glomerular TMA and one had vascular TMA. Eight (40%) had no glomerular immune deposits and 12 (60%) showed only mesangial immune deposits. The acute tubulointerstitial injury in patients requiring dialysis was more severe than those not needing dialysis ((43.6 ± 24.9) % vs. (21.7 ± 20.1) %, p = 0.047). FPE of podocytes was positively correlated with proteinuria (r2 = 0.347, p = 0.006). All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange. The renal function of 11 patients requiring dialysis initially recovered after 16.0 (interquartile range [IQR] 9.0, 30.0) days of treatment. During the follow-up of 58.0 (IQR 36.0, 92.3) months, remission was achieved in 19 (95%) patients; only one patient had no response. No patient died or progressed to end-stage renal disease; six patients (30%) relapsed. CONCLUSION: Renal TMA, usually accompanying severe renal injury, was not uncommon in SLE patients with renal disease and should be distinguished from immune complex-mediated severe classes of LN. Early intensive immunosuppressive treatment may be associated with a good long-term renal outcome. Key Points • Most previous reports of renal TMA in SLE patients were associated with severe types of immune complex-mediated lupus nephritis; • Renal TMA with glomerular pauci-immune or only mesangial immune deposits was found in SLE patients and clinically presented with severe acute renal injury but good renal outcome; • Renal TMA should be considered as a unique type of SLE-associated renal injury.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Microangiopatias Trombóticas , Humanos , Rim , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/complicações , Nefrite Lúpica/terapia , Diálise Renal , Estudos Retrospectivos , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/terapia
16.
Ann Palliat Med ; 10(1): 767-777, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33474943

RESUMO

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but severe pulmonary complication of malignant tumors. It is characterized by the presence of multiple microscopic tumor emboli attached to the endothelium of small pulmonary arteries and induces fibrointimal proliferation and the activation of coagulation. The main clinical manifestations of PTTM are dyspnea, dry cough, hypoxemia, pulmonary hypertension, right heart failure, thrombocytopenia, and disseminated intravascular coagulation (DIC). Chest computed tomography (CT) shows no distinctive findings, and PTTM is often unrecognized and universally underdiagnosed, with an appalling prognosis. An antemortem diagnosis of PTTM is also difficult due to a lack of specific clinical and imaging features. Moreover, there is presently no therapeutic management and the illness rapidly progresses to death. Early identification and timely and effective use of oncotherapy can help to alleviate symptoms and improve prognosis. According to recent reports, targeting angiogenesis factors including platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) have marginally improved survival. In this article, we report the case of a patient with advanced lung adenocarcinoma complicated with PTTM and DIC. A combined therapeutic regimen of bevacizumab with pemetrexed successfully improved chest CT findings, respiratory symptoms, DIC, and short-term outcomes. Anti-angiogenesis drugs modify the pulmonary vascular structure, and rapidly improve the lung tumor microenvironment. And therefore, it may be a potentially effective drug for the treatment of PTTM.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Microangiopatias Trombóticas , Adenocarcinoma de Pulmão/tratamento farmacológico , Bevacizumab/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/uso terapêutico , Microangiopatias Trombóticas/tratamento farmacológico , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular
19.
Front Immunol ; 11: 610696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343584

RESUMO

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.


Assuntos
Proteína ADAMTS13/imunologia , Armadilhas Extracelulares/imunologia , Trombose/imunologia , Fator de von Willebrand/imunologia , Doença Aguda , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Isquemia Encefálica/virologia , Humanos , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia , Trombose/patologia , Trombose/virologia , Microangiopatias Trombóticas/imunologia , Microangiopatias Trombóticas/patologia , Microangiopatias Trombóticas/virologia
20.
Adv Chronic Kidney Dis ; 27(5): 365-376, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33308501

RESUMO

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.


Assuntos
Injúria Renal Aguda/metabolismo , Citocinas/metabolismo , Glomerulonefrite/metabolismo , Microangiopatias Trombóticas/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Antibacterianos/efeitos adversos , Antivirais/efeitos adversos , Apolipoproteína L1/genética , Ácido Ascórbico/efeitos adversos , Azotemia/metabolismo , Azotemia/patologia , Azotemia/fisiopatologia , /patologia , Progressão da Doença , Glomerulonefrite/patologia , Glomerulonefrite/fisiopatologia , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/fisiopatologia , Mortalidade Hospitalar , Humanos , Túbulos Renais Proximais/lesões , Tempo de Internação , Mioglobina/metabolismo , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Nefrite Intersticial/fisiopatologia , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Nefrose Lipoide/fisiopatologia , Insuficiência Renal Crônica , Rabdomiólise/metabolismo , Índice de Gravidade de Doença , Microangiopatias Trombóticas/patologia , Microangiopatias Trombóticas/fisiopatologia , Vitaminas/efeitos adversos
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