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1.
Hipertens. riesgo vasc ; 37(3): 101-107, jul.-sept. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193518

RESUMO

INTRODUCTION: Blood pressure (BP) control is fundamental to the care of patients with chronic kidney disease (CKD), and is relevant at all stages of CKD. Renin-angiotensin-aldosterone system (RAAS) blockers have shown to be effective, not only in BP control but also in reducing proteinuria and slowing CKD progression. However, there is a lack of evidence for recommending RAAS blockers in elderly patients with CKD without proteinuria. The primary outcome of the present study is to evaluate the impact of RAAS blockers on CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: The PROERCAN trial (trial registration, NCT03195023) is a multicentre open-label, randomized controlled clinical trial with 110 participants over 65 years-old with hypertension and CKD stages 3-4 without proteinuria. Patients will be randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs, and will be followed up for three years. Primary outcome is the estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcomes include BP control, renal and cardiovascular events, and mortality. RESULTS AND CONCLUSIONS: The design of this trial is presented here. The results will show if antihypertensive treatment with RAAS blockers has an impact on CKD progression in elderly patients without proteinuria. Any differences in BP control, cardiovascular events, and mortality with each antihypertensive treatment will be also clarified


INTRODUCCIÓN: El control de la presión arterial (PA) es fundamental para los pacientes con enfermedad renal crónica (ERC) y es relevante en todos los estadios de ERC. Los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) han demostrado su efectividad no solo en el control de la PA sino también en la reducción de la proteinuria y de la progresión de la ERC. Sin embargo, no existe evidencia para recomendar el uso de BSRAA en pacientes añosos con ERC sin proteinuria. El objetivo principal del estudio es evaluar el impacto de los BSRAA en la progresión de ERC en pacientes añosos sin proteinuria. MATERIAL Y MÉTODOS: El estudio PROERCAN (NCT03195023) es un ensayo clínico multicéntrico, abierto, aleatorizado de 110 pacientes hipertensos, mayores de 65 años con ERC estadios3 y4 sin proteinuria. Los pacientes son aleatorizados 1:1 a recibir tratamiento con BSRAA u otros antihipertensivos y el seguimiento será de 3años. La variable principal es el descenso del filtrado glomerular estimado durante el tiempo de seguimiento. Las variables secundarias incluyen las cifras de PA, eventos renales y cardiovasculares y mortalidad. RESULTADOS Y CONCLUSIÓN: El diseño del ensayo clínico se desarrolla en el presente artículo. Los resultados determinarán si el tratamiento antihipertensivo con BSRAA tiene un impacto en la progresión de la ERC en pacientes añosos sin proteinuria. Así mismo, se aclararán las diferencias en el control de la PA, los eventos cardiovasculares y la mortalidad con los distintos tratamientos antihipertensivos


Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Sistema Renina-Angiotensina/efeitos dos fármacos , Insuficiência Renal Crônica/terapia , Proteinúria/etiologia , Progressão da Doença , Proteinúria/terapia , Taxa de Filtração Glomerular
2.
BMC Med Genet ; 21(1): 183, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957924

RESUMO

BACKGROUND: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. CASE PRESENTATION: Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography-mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. CONCLUSIONS: Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Hiper-Homocisteinemia/complicações , Proteinúria/diagnóstico , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/genética , Aminoácidos/sangue , Sequência de Bases , Carnitina/análogos & derivados , Carnitina/sangue , Pré-Escolar , DNA/sangue , DNA/genética , Cromatografia Gasosa-Espectrometria de Massas , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/genética , Masculino , Ácido Metilmalônico/urina , Proteinúria/etiologia
5.
Medicine (Baltimore) ; 99(39): e22341, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991448

RESUMO

RATIONALE: The Goodpasture syndrome is an extremely rare disease, with renal and pulmonary manifestations, and is mediated by anti-glomerular basement membrane (anti-GBM) antibodies. Renal pathological changes are mainly characterized by glomerular crescent formation and linear immunofluorescent staining for immunoglobulin G on the GBM. There are few reports on the atypical course of the syndrome involving serum-negative anti-GBM antibodies. Therefore, we present a case of Goodpasture syndrome that presented with nephrotic-range proteinuria and was seronegative for anti-GBM antibodies. PATIENT CONCERNS: A 38-year-old Chinese man presented with a lung lesion that was discovered by physical examination a month prior to presentation. The chief concern was occasional hemoptysis without fever, cough, chest pain, and edema. DIAGNOSES: Laboratory testing revealed that the urinary protein level and urine erythrocyte count were 7.4 g/24 hours and 144/high-power field (HPF), respectively. Serological testing for anti-GBM antibodies was negative. Chest computed tomography revealed multiple exudative lesions in both lungs, indicating alveolar infiltration and hemorrhage. Electronic bronchoscopy and pathological examination of the alveolar lavage fluid indicated no abnormalities. However, kidney biopsy suggested cellular crescent formation and segmental necrosis of the globuli, with linear IgG and complement C3 deposition on the GBM. These findings were consistent with the diagnosis of anti-GBM antibody nephritis. INTERVENTIONS: The patient underwent 7 sessions of double filtration plasmapheresis. He was also administered with intravenous methylprednisolone and cyclophosphamide. After renal function stabilization, he was discharged under an immunosuppressive regimen comprising of glucocorticoids and cyclophosphamides. OUTCOMES: Three months later, follow-up examination revealed that the 24-hour urine protein had increased to 13 g. Furthermore, the urine erythrocyte count was 243/HPF. After a 6-month follow-up, the patient achieved partial remission, with a proteinuria level of 3.9 g/24 hours and a urine erythrocyte count of 187/HPF. LESSONS: This extremely rare case of Goodpasture syndrome manifested with seronegativity for anti-GBM antibodies and nephrotic-range proteinuria. Our findings emphasize the importance of renal biopsy for the clinical diagnosis of atypical cases. Furthermore, because renal involvement achieved only partial remission despite therapy, early detection and active treatment of the Goodpasture syndrome is necessary to improve the prognosis of patients.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/imunologia , Autoanticorpos/sangue , Proteinúria/etiologia , Administração Intravenosa , Adulto , Assistência ao Convalescente , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Grupo com Ancestrais do Continente Asiático/etnologia , Complemento C3/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemoptise/diagnóstico , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Nefrite/diagnóstico , Nefrite/imunologia , Plasmaferese/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
6.
Rev Assoc Med Bras (1992) ; 66Suppl 2(Suppl 2): 112-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965368

RESUMO

OBJECTIVE: We aimed to present a review of renal changes in patients with COVID-19. METHODS: We performed a systematic review of the literature to identify original articles regarding clinical, laboratory, and anatomopathological kidney changes in patients infected with SARS-CoV-2 published until May 7, 2020. The search was carried out across PubMed, Scopus, and Embase using the keywords "COVID-19", "coronavirus", "SARS-CoV-2", "kidney injury" and "kidney disease". Fifteen studies presented clinical and laboratory renal changes in patients with COVID-19, and three addressed anatomopathological changes. DISCUSSION: Acute kidney injury (AKI) was a relevant finding in patients with COVID-19. There were also significant changes in laboratory tests that indicated kidney injury, such as increased serum creatinine and blood urea nitrogen (BUN), proteinuria, and hematuria. The presence of laboratory abnormalities and AKI were significant in severely ill patients. There was a considerable prevalence of AKI among groups of patients who died of COVID-19. Histopathological analysis of the kidney tissue of patients infected with SARS-CoV-2 suggested that the virus may directly affect the kidneys. CONCLUSION: Although COVID-19 affects mainly the lungs, it can also impact the kidneys. Increased serum creatinine and BUN, hematuria, proteinuria, and AKI were frequent findings in patients with severe COVID-19 and were related to an increased mortality rate. Further studies focusing on renal changes and their implications for the clinical condition of patients infected with the novel coronavirus are needed.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Lesão Renal Aguda/fisiopatologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/urina , Creatinina/sangue , Hematúria/etiologia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/urina , Proteinúria/etiologia , Urina/química
7.
Transplantation ; 104(8): 1695-1702, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732849

RESUMO

BACKGROUND: Reports about prognosis of adults receiving small pediatric-donor kidneys (PDK) as compared to those receiving elder pediatric or adult donor kidneys (ADKs) are controversial. This study aimed to examine the outcomes of adults receiving small PDK and possible prognostic factors. METHODS: The records of adults who received kidneys from donors < 10 years old at our center from July 1, 2011 to June 30, 2018 were reviewed. RESULTS: A total of 121 adults were small PDK recipients. Twenty-three patients received 29 biopsies or nephrectomy between 6 and 896 days posttransplantation days. Seven patients (30.4%) had pediatric donor glomerulopathy (PDG), which developed from 113 to 615 days posttransplantation. The incidence of proteinuria and hematuria was significantly higher in the PDG group. The characteristic pathological finding in PDG was irregular lamination and splintering of the glomerular basement membrane (GBM). Donor age, donor weight, and donor kidney volume were significantly less in PDG cases compared with the non-PDG cases. For the risk factors of PDG, increasing urinary RBC count during follow-up was an independent predictor, while increasing donor age and body weight were protective factors. PDG was not a significant risk factor for Scr increasing of PDKs. CONCLUSIONS: PDG is a potential cause of abnormal urinalysis in adults receiving small PDKs. The pathological characteristic change of PDG is splitting and lamination of GBM. Persistent hematuria after transplantation in recipients of PDK is a predictor of PDG development.


Assuntos
Glomerulonefrite/patologia , Hematúria/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Proteinúria/epidemiologia , Adolescente , Adulto , Fatores Etários , Aloenxertos/anatomia & histologia , Aloenxertos/patologia , Biópsia , Peso Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Membrana Basal Glomerular/patologia , Sobrevivência de Enxerto , Hematúria/etiologia , Hematúria/patologia , Hematúria/urina , Humanos , Lactente , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/urina , Prognóstico , Fatores de Proteção , Proteinúria/etiologia , Proteinúria/patologia , Proteinúria/urina , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento , Adulto Jovem
10.
Medicine (Baltimore) ; 99(29): e20678, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702818

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is among the common and serious complications of diabetes and is also a major cause of end-stage kidney disease. Early DN is also called diabetic microalbumin period, the main treatment is in the control of blood sugar on the basis of kidney protection and urine lowering protein. There are few effective methods of western medicine treatment, and most of them are accompanied by adverse reactions. But some studies have shown that traditional Chinese medicine has achieved the curative effect and has certain superiority. However, there are few systematic reviews on the treatment of traditional Chinese herbal medicine for early DN currently. Therefore, this study conducted a systematic review of clinical efficacy and safety of Chinese herbal medicine for the treatment of patients with early DN, aim to comprehensively analyze the role of traditional Chinese herbal medicine in the treatment of early DN. METHODS AND ANALYSIS: The protocol of this systematic review and meta-analysis was registered on the INPLASY website (https://inplasy.com/inplasy-2020-4-0139/) and INPLASY registration number is INPLASY202040139. A systematic literature search will be conducted in 3 English database and 4 Chinese databases with a language limitation of English and Chinese. Search for clinical research literature on Chinese herbal medicine treatment of DN published in domestic and foreign biomedical journals. The time is limited from January 2010 to February 2020. We will investigate heterogeneity across studies and publication bias. To assess the risk of bias and quality of the included studies, we will use the Cochrane Collaboration's ROB tool. According to the relevant standards in the Cochrane Intervention System Evaluation Manual, it will be divided into low risk, high risk, and unclear. We will also use the RevMan 5.3 software and Stata 13.0 software for meta-analysis of the effectiveness and symptom scores of DN proteinuria. ETHICS AND DISSEMINATION: The ethical considerations are not required because the systematic review is based on published studies. The systematic review and meta-analysis will be published in a peer-reviewed Journal.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Complicações do Diabetes/epidemiologia , Nefropatias Diabéticas/classificação , Nefropatias Diabéticas/complicações , Feminino , Humanos , Falência Renal Crônica/etiologia , Masculino , Proteinúria/diagnóstico , Proteinúria/etiologia , Proteinúria/urina , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Sensibilidade e Especificidade , Resultado do Tratamento
11.
Clin Rheumatol ; 39(9): 2811-2815, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32720260

RESUMO

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.


Assuntos
Síndrome Antifosfolipídica/imunologia , Infecções por Coronavirus/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Pneumonia Viral/imunologia , Adolescente , Anemia/etiologia , Anticorpos Anticardiolipina/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Anuria/etiologia , Betacoronavirus , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Complemento C3/imunologia , Complemento C4/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , DNA/imunologia , Ecocardiografia , Evolução Fatal , Feminino , Parada Cardíaca/etiologia , Hematúria/etiologia , Humanos , Inibidor de Coagulação do Lúpus/imunologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Pandemias , Posicionamento do Paciente , Pericardiocentese , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Decúbito Ventral , Proteinúria/etiologia , Diálise Renal , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Respiração Artificial , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Trombocitopenia/etiologia , Trombose Venosa/etiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
12.
PLoS One ; 15(7): e0235759, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634168

RESUMO

BACKGROUND: Renal abnormalities in HIV infected children may be due to the HIV infection or treatment among other factors. Tenofovir disoproxil fumarate (TDF) is associated with proximal renal tubular dysfunction, proteinuria and decrease in glomerular function. Studies in developed countries have shown variable prevalence of proximal renal tubular dysfunction in children on TDF. There are no known studies in developing countries, including Zimbabwe, documenting the proximal tubular function in HIV infected children on TDF. The aim of this study was to assess renal and proximal renal tubular function in HIV infected children receiving TDF and determine factors associated with proximal tubular dysfunction. METHODS: A descriptive cross-sectional study was conducted in HIV infected patients below 18 years of age attending outpatient clinics at two tertiary hospitals in Harare, who received a TDF-containing antiretroviral regimen for at least six months. Dipstick protein and glucose, serum and urine phosphate and creatinine levels were measured. Fractional excretion of phosphate was calculated. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Tubular dysfunction was defined by at least two of the following characteristics: normoglycaemic glycosuria, hypophosphatemia and fractional excretion of phosphate > 18%. FINDINGS: One hundred and ninety-eight children below 18 years of age were recruited over a period of six months. The prevalence of tubular dysfunction was 0.5%. Normoglycaemic glycosuria occurred in 1 (0.5%), fractional excretion of phosphate >18% in 4 (2%), and hypophosphatemia in 22 [11.1%] patients. Severe stunting was associated with increased risk of hypophosphatemia (OR 9.31 CI (1.18, 80.68) p = 0.03). Reduction in estimated glomerular filtration rate (eGFR) < 90ml/min/1.73m2 and proteinuria was evident in 35.9% and 32.8% of children, respectively. Concurrent TDF and HIV-1 protease inhibitor-based regimen was the only independent factor associated with reduction in GFR (OR 4.43 CI (1.32; 4.89) p = 0.016). CONCLUSION: Tubular dysfunction was uncommon in Zimbabwean children on a TDF-based ART regimen. Hypophosphatemia, proteinuria and reduction in eGFR were common. Reassessing renal function using more sensitive biomarkers is needed to examine the long-term tolerance of TDF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Síndrome de Fanconi/etiologia , Infecções por HIV/complicações , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico , Adolescente , Fármacos Anti-HIV/efeitos adversos , Criança , Estudos Transversais , Síndrome de Fanconi/induzido quimicamente , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Proteinúria/etiologia , Inibidores da Transcriptase Reversa/efeitos adversos , Tenofovir/efeitos adversos , Centros de Atenção Terciária , Zimbábue
14.
JAMA ; 324(1): 79-89, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633805

RESUMO

Importance: Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe. Objective: To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis. Evidence Review: A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature. Findings: There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype. Conclusions and Relevance: All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Algoritmos , Benzoxazóis/uso terapêutico , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Inativação Gênica , Insuficiência Cardíaca/etiologia , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Transplante de Fígado , Melfalan/uso terapêutico , Prognóstico , Proteinúria/etiologia , Transplante de Células-Tronco
15.
Intensive Care Med ; 46(7): 1339-1348, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32533197

RESUMO

Acute kidney injury (AKI) has been reported in up to 25% of critically-ill patients with SARS-CoV-2 infection, especially in those with underlying comorbidities. AKI is associated with high mortality rates in this setting, especially when renal replacement therapy is required. Several studies have highlighted changes in urinary sediment, including proteinuria and hematuria, and evidence of urinary SARS-CoV-2 excretion, suggesting the presence of a renal reservoir for the virus. The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. Non-specific mechanisms include haemodynamic alterations, right heart failure, high levels of PEEP in patients requiring mechanical ventilation, hypovolemia, administration of nephrotoxic drugs and nosocomial sepsis. To date, there is no specific treatment for COVID-19 induced AKI. A number of investigational agents are being explored for antiviral/immunomodulatory treatment of COVID-19 and their impact on AKI is still unknown. Indications, timing and modalities of renal replacement therapy currently rely on non-specific data focusing on patients with sepsis. Further studies focusing on AKI in COVID-19 patients are urgently warranted in order to predict the risk of AKI, to identify the exact mechanisms of renal injury and to suggest targeted interventions.


Assuntos
Lesão Renal Aguda/virologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Sistema Renina-Angiotensina/fisiologia , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/terapia , Betacoronavirus/fisiologia , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/urina , Creatinina/sangue , Estado Terminal , Hematúria/etiologia , Humanos , Rim/fisiopatologia , Rim/virologia , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/urina , Proteinúria/etiologia , Urinálise , Urina/química , Urina/virologia
16.
Scand J Immunol ; 92(3): e12915, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32533866

RESUMO

Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. Together with B cells, respective self-reactive T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secretion, B cell activation and promoting amplification of the autoimmune response. Annexin A1 is expressed by many cell types and binds to phospholipids in a Ca2+ -dependent manner. Abnormal expression of annexin A1 was found on activated B and T cells in both murine and human autoimmunity suggesting its potential role as a therapeutic target. In the present study, we have investigated the possibility to suppress autoimmune manifestation in spontaneous mouse model of lupus using anti-annexin A1 antibody. Groups of lupus-prone MRL/lpr mice were treated with the anti-annexin A1 monoclonal antibody, and the disease activity and survival of the animals were following up. Flow cytometry, ELISA assays, and histological and immunofluorescence kidney analyses were used to determine the levels of Annexin A1 expression, cytokines, anti-dsDNA antibodies and kidney injuries. The administration of this monoclonal antibody to MRL/lpr mice resulted in suppression of IgG anti-dsDNA antibody production, modulated IL-10 secretion, decreased disease activity and prolonged survival compared with the control group.


Assuntos
Anexina A1/antagonistas & inibidores , Anexina A1/imunologia , Anticorpos Monoclonais/farmacologia , Fatores Imunológicos/farmacologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Animais , Autoanticorpos/imunologia , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Humanos , Imunoglobulina G/imunologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Camundongos , Camundongos Endogâmicos MRL lpr , Proteinúria/etiologia , Proteinúria/urina , Baço/imunologia , Baço/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do Tratamento
17.
BJOG ; 127(11): 1374-1380, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479682

RESUMO

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Síndrome HELLP/fisiopatologia , Fator de Crescimento Placentário/metabolismo , Pneumonia Viral/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Complicações Infecciosas na Gravidez/fisiopatologia , Artéria Uterina/diagnóstico por imagem , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Betacoronavirus , Pressão Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Feminino , Síndrome HELLP/etiologia , Síndrome HELLP/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Proteinúria/etiologia , Proteinúria/fisiopatologia , Fluxo Pulsátil , Índice de Gravidade de Doença , Centros de Atenção Terciária , Trombocitopenia/etiologia , Trombocitopenia/fisiopatologia
18.
Am J Kidney Dis ; 76(2): 295-297, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32362418
19.
J Am Soc Nephrol ; 31(6): 1157-1165, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-154772

RESUMO

BACKGROUND: Some patients with COVID-19 pneumonia also present with kidney injury, and autopsy findings of patients who died from the illness sometimes show renal damage. However, little is known about the clinical characteristics of kidney-related complications, including hematuria, proteinuria, and AKI. METHODS: In this retrospective, single-center study in China, we analyzed data from electronic medical records of 333 hospitalized patients with COVID-19 pneumonia, including information about clinical, laboratory, radiologic, and other characteristics, as well as information about renal outcomes. RESULTS: We found that 251 of the 333 patients (75.4%) had abnormal urine dipstick tests or AKI. Of 198 patients with renal involvement for the median duration of 12 days, 118 (59.6%) experienced remission of pneumonia during this period, and 111 of 162 (68.5%) patients experienced remission of proteinuria. Among 35 patients who developed AKI (with AKI identified by criteria expanded somewhat beyond the 2012 Kidney Disease: Improving Global Outcomes definition), 16 (45.7%) experienced complete recovery of kidney function. We suspect that most AKI cases were intrinsic AKI. Patients with renal involvement had higher overall mortality compared with those without renal involvement (28 of 251 [11.2%] versus one of 82 [1.2%], respectively). Stepwise multivariate binary logistic regression analyses showed that severity of pneumonia was the risk factor most commonly associated with lower odds of proteinuric or hematuric remission and recovery from AKI. CONCLUSIONS: Renal abnormalities occurred in the majority of patients with COVID-19 pneumonia. Although proteinuria, hematuria, and AKI often resolved in such patients within 3 weeks after the onset of symptoms, renal complications in COVID-19 were associated with higher mortality.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Hematúria/etiologia , Pneumonia Viral/complicações , Proteinúria/etiologia , Adulto , Idoso , Infecções por Coronavirus/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Prognóstico , Estudos Retrospectivos
20.
Am J Kidney Dis ; 76(3): 350-360, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32336487

RESUMO

RATIONALE & OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that the use of histopathologic features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING & PARTICIPANTS: All 2,720 individuals from the Biopsy Biobank Cohort of Indiana who underwent kidney biopsy between 2002 and 2015 and had at least 2 years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbid conditions, baseline clinical characteristics, and histopathologic features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate ≤ 10mL/min/1.73m2. ANALYTICAL APPROACH: Multivariable Cox regression model with internal validation by bootstrapping. Models including clinical and demographic variables were fit with the addition of histopathologic features. To assess the impact of adding a histopathology variable, the amount of variance explained (r2) and the C index were calculated. The impact on prediction was assessed by calculating the net reclassification index for each histopathologic variable and for all combined. RESULTS: Median follow-up was 3.1 years. Within 5 years of biopsy, 411 (15.1%) patients developed kidney failure. Multivariable analyses including demographic and clinical variables revealed that severe glomerular obsolescence (adjusted HR, 2.03; 95% CI, 1.51-2.03), severe interstitial fibrosis and tubular atrophy (adjusted HR, 1.99; 95% CI, 1.52-2.59), and severe arteriolar hyalinosis (adjusted HR, 1.53; 95% CI, 1.14-2.05) were independently associated with the primary outcome. The addition of all histopathologic variables to the clinical model yielded a net reclassification index for kidney failure of 5.1% (P < 0.001) with a full model C statistic of 0.915. Analyses addressing the competing risk for death, optimism, or shrinkage did not significantly change the results. LIMITATIONS: Selection bias from the use of clinically indicated biopsies and exclusion of patients with less than 2 years of follow-up, as well as reliance on surrogate indicators of kidney failure onset. CONCLUSIONS: A model incorporating histopathologic features from kidney biopsy specimens improved prediction of kidney failure and may be valuable clinically. Future studies will be needed to understand whether even more detailed characterization of kidney tissue may further improve prognostication about the future trajectory of estimated glomerular filtration rate.


Assuntos
Rim/patologia , Insuficiência Renal/patologia , Adolescente , Adulto , Biópsia , Comorbidade , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/epidemiologia , Proteinúria/etiologia , Insuficiência Renal/complicações , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
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