Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.970
Filtrar
1.
J Am Soc Nephrol ; 31(9): 2205-2221, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32826326

RESUMO

BACKGROUND: The incidence, severity, and outcomes of AKI in COVID-19 varied in different reports. In patients critically ill with COVID-19, the clinicopathologic characteristics of AKI have not been described in detail. METHODS: This is a retrospective cohort study of 81 patients critically ill with COVID-19 in an intensive care unit. The incidence, etiologies, and outcomes of AKI were analyzed. Pathologic studies were performed in kidney tissues from ten deceased patients with AKI. RESULTS: A total of 41 (50.6%) patients experienced AKI in this study. The median time from illness to AKI was 21.0 (IQR, 9.5-26.0) days. The proportion of Kidney Disease Improving Global Outcomes (KDIGO) stage 1, stage 2, and stage 3 AKI were 26.8%, 31.7%, and 41.5%, respectively. The leading causes of AKI included septic shock (25 of 41, 61.0%), volume insufficiency (eight of 41, 19.5%), and adverse drug effects (five of 41, 12.2%). The risk factors for AKI included age (per 10 years) (HR, 1.83; 95% CI, 1.24 to 2.69; P=0.002) and serum IL-6 level (HR, 1.83; 95% CI, 1.23 to 2.73; P=0.003). KDIGO stage 3 AKI predicted death. Other potential risk factors for death included male sex, elevated D-dimer, serum IL-6 level, and higher Sequential Organ Failure Assessment score. The predominant pathologic finding was acute tubular injury. Nucleic acid tests and immunohistochemistry failed to detect the virus in kidney tissues. CONCLUSIONS: AKI was a common and multifactorial complication in patients critically ill with COVID-19 at the late stage of the disease course. The predominant pathologic finding was acute tubular injury. Older age and higher serum IL-6 level were risk factors of AKI, and KDIGO stage 3 AKI independently predicted death.


Assuntos
Lesão Renal Aguda/patologia , Betacoronavirus , Infecções por Coronavirus/complicações , Rim/patologia , Pneumonia Viral/complicações , Lesão Renal Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/patologia , Creatinina/sangue , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , Rim/ultraestrutura , Rim/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Fatores de Risco
2.
Lancet ; 396(10247): 320-332, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682491

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/ultraestrutura , Células Epiteliais Alveolares/virologia , Autopsia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Feminino , Trato Gastrointestinal/patologia , Trato Gastrointestinal/ultraestrutura , Trato Gastrointestinal/virologia , Coração/virologia , Humanos , Rim/patologia , Rim/ultraestrutura , Rim/virologia , Fígado/patologia , Fígado/ultraestrutura , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Miocárdio/ultraestrutura , Pandemias , Pneumonia Viral/epidemiologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Mucosa Respiratória/patologia , Mucosa Respiratória/ultraestrutura , Mucosa Respiratória/virologia , Baço/patologia , Baço/ultraestrutura , Baço/virologia , Trombose/patologia , Traqueia/patologia , Traqueia/ultraestrutura , Traqueia/virologia , Washington/epidemiologia
3.
J Am Soc Nephrol ; 31(9): 1948-1958, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32660970

RESUMO

BACKGROUND: Reports show that AKI is a common complication of severe coronavirus disease 2019 (COVID-19) in hospitalized patients. Studies have also observed proteinuria and microscopic hematuria in such patients. Although a recent autopsy series of patients who died with severe COVID-19 in China found acute tubular necrosis in the kidney, a few patient reports have also described collapsing glomerulopathy in COVID-19. METHODS: We evaluated biopsied kidney samples from ten patients at our institution who had COVID-19 and clinical features of AKI, including proteinuria with or without hematuria. We documented clinical features, pathologic findings, and outcomes. RESULTS: Our analysis included ten patients who underwent kidney biopsy (mean age: 65 years); five patients were black, three were Hispanic, and two were white. All patients had proteinuria. Eight patients had severe AKI, necessitating RRT. All biopsy samples showed varying degrees of acute tubular necrosis, and one patient had associated widespread myoglobin casts. In addition, two patients had findings of thrombotic microangiopathy, one had pauci-immune crescentic GN, and another had global as well as segmental glomerulosclerosis with features of healed collapsing glomerulopathy. Interestingly, although the patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR, immunohistochemical staining of kidney biopsy samples for SARS-CoV-2 was negative in all ten patients. Also, ultrastructural examination by electron microscopy showed no evidence of viral particles in the biopsy samples. CONCLUSIONS: The most common finding in our kidney biopsy samples from ten hospitalized patients with AKI and COVID-19 was acute tubular necrosis. There was no evidence of SARS-CoV-2 in the biopsied kidney tissue.


Assuntos
Lesão Renal Aguda/patologia , Betacoronavirus , Infecções por Coronavirus/complicações , Rim/patologia , Pneumonia Viral/complicações , Idoso , Biópsia , Infecções por Coronavirus/patologia , Feminino , Humanos , Rim/ultraestrutura , Necrose Tubular Aguda/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia
5.
J Am Soc Nephrol ; 31(9): 2158-2167, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32727719

RESUMO

BACKGROUND: AKI is common among hospitalized patients with coronavirus disease 2019 (COVID-19) and is an independent risk factor for mortality. Although there are numerous potential mechanisms underlying COVID-19-associated AKI, our current knowledge of kidney pathologic findings in COVID-19 is limited. METHODS: We examined the postmortem kidneys from 42 patients who died of COVID-19. We reviewed light microscopy findings in all autopsies and performed immunofluorescence, electron microscopy, and in situ hybridization studies for SARS-CoV-2 on a subset of samples. RESULTS: The cohort had a median age of 71.5 years (range, 38-97 years); 69% were men, 57% were Hispanic, and 73% had a history of hypertension. Among patients with available data, AKI developed in 31 of 33 patients (94%), including 6 with AKI stage 1, 9 with stage 2, and 16 with stage 3. The predominant finding correlating with AKI was acute tubular injury. However, the degree of acute tubular injury was often less severe than predicted for the degree of AKI, suggesting a role for hemodynamic factors, such as aggressive fluid management. Background changes of hypertensive arterionephrosclerosis and diabetic glomerulosclerosis were frequent but typically mild. We identified focal kidney fibrin thrombi in 6 of 42 (14%) autopsies. A single Black patient had collapsing FSGS. Immunofluorescence and electron microscopy were largely unrevealing, and in situ hybridization for SARS-CoV-2 showed no definitive positivity. CONCLUSIONS: Among a cohort of 42 patients dying with COVID-19, autopsy histologic evaluation revealed acute tubular injury, which was typically mild relative to the degree of creatinine elevation. These findings suggest potential for reversibility upon resolution of SARS-CoV-2 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/patologia , Rim/patologia , Pneumonia Viral/patologia , Lesão Renal Aguda/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Rim/ultraestrutura , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Pandemias
6.
J Am Soc Nephrol ; 31(9): 1959-1968, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32680910

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. METHODS: We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. CONCLUSIONS: Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.


Assuntos
Betacoronavirus , Infecções por Coronavirus/patologia , Rim/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus/isolamento & purificação , Biópsia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Feminino , Humanos , Rim/ultraestrutura , Rim/virologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/imunologia
10.
Int. j. morphol ; 38(2): 461-471, abr. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1056463

RESUMO

This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.


Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.


Assuntos
Animais , Masculino , Ratos , Vitamina E/farmacologia , Lesão Renal Aguda/induzido quimicamente , Artemeter/toxicidade , Vitamina E/administração & dosagem , Microscopia Eletrônica , Biomarcadores/análise , Ratos Wistar , Rim/efeitos dos fármacos , Rim/patologia , Rim/ultraestrutura , Antimaláricos/toxicidade
11.
Kidney Int ; 98(1): 219-227, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32327202

RESUMO

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus-like particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.


Assuntos
Infecções por Coronavirus/patologia , Rim/ultraestrutura , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
12.
Ecotoxicol Environ Saf ; 192: 110256, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32014724

RESUMO

The modulatory role of the Spirulina platensis (SP) against furan-induced (FU) hepatic and renal damage was assessed in this study. For achieving this, sixty rats were distributed into six groups: control group, SP-administered group (300 mg/kg b.wt orally for 28 days), a FU-intoxicated group (16 mg/kg b.wt, orally, daily for 28 days), protective co-treated group SP/F (administered SP 300 mg/kg b.wt, one week before, and concurrently with FU intoxication), therapeutic co-treated group FU/SP (administered SP 300 mg/kg b.wt, one week after FU intoxication for 28 days) and protective/therapeutic co-treated group SP/FU/SP (administered SP one week before and after, concurrently with FU intoxication). Subsequently, the biochemical responses and the histology of hepatic and renal tissues in treated rats were assessed. The results indicated that FU intoxication induced a significant hepato- and nephropathy represented by the elevation in the values of tissue injury biomarkers and reduction in protein levels. Histologically, a wide range of morphological, cytotoxic, inflammatory, and vascular alterations as well as downregulation in the immunoexpression of the proliferating cell nuclear antigen (PCNA) and the proliferation-associated nuclear antigen (Ki-67) were induced by FU intoxication. Oral SP administration, particularly in the protective/therapeutic co-treated group, markedly supressed the serum levels of the tissue injury biomarkers, diminished the inflammatory response, restored the cytotoxic alterations, upregulated the immunoexpression of PCNA and Ki-67, and restored the perturbed morphology of the hepatic and renal tissues. In conclusion, the obtained data demonstrated that SP co-administration elicits both protective and therapeutic potential against the FU-induced hepato- and nephropathy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/terapia , Furanos/toxicidade , Nefropatias/terapia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Spirulina , Animais , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Antígeno Ki-67/metabolismo , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos
14.
Artif Organs ; 44(1): 81-90, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31368159

RESUMO

Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome to sudden rewarming to normothermic. However, the identification of an oxygen carrier that could function at a temperature range from 4 to 7°C or whether it is necessary to use oxygen carrier during kidney rewarming, remains unresolved. This study was designed to test the use of a hemoglobin-based oxygen carrier (HBOC) during gradual kidney rewarming as an alternative to simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into the control and the HBOC group. In the control group, no oxygen carrier was used during rewarming perfusion and the perfusion solution was oxygenated only by applying diffused carbogen flow. The protocol mimicked a donor after circulatory death (DCD) kidney transplantation, where after 30 minutes warm ischemia and 120 minutes cold storage in University of Wisconsin solution, the DCD kidneys underwent gradual rewarming from 10 to 37°C during 90 minutes with or without HBOC. This was followed by 30 minutes of warm ischemia in room temperature to mimic the anastomosis time and 120 minutes of reperfusion at 37°C to mimic the early post-transplant state of the graft. The HBOC group demonstrated superior kidney function which was highlighted by higher ultrafiltrate production, better glomerular filtration rate and improved sodium reabsorption. There was no significant difference between the 2 groups regarding the hemodynamics, tissue injury, and adenosine triphosphate levels. In conclusion, this study suggests better renal function recovery in DCD kidneys after rewarming with HBOC compared to rewarming without an oxygen carrier.


Assuntos
Substitutos Sanguíneos/farmacologia , Hemoglobinas/farmacologia , Rim/fisiologia , Preservação de Órgãos/métodos , Animais , Desenho de Equipamento , Rim/efeitos dos fármacos , Rim/ultraestrutura , Masculino , Preservação de Órgãos/instrumentação , Consumo de Oxigênio/efeitos dos fármacos , Perfusão/instrumentação , Perfusão/métodos , Ratos , Ratos Endogâmicos Lew , Reaquecimento/instrumentação , Reaquecimento/métodos
15.
Micron ; 130: 102797, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31862481

RESUMO

Scanning electron microscopy (SEM) use in the biomedical sciences has traditionally been used for characterisation of cell and tissue surface topography. This paper demonstrates the utility of high-resolution scanning electron microscopy (HRSEM) to diagnostic pathology and cell biology ultrastructural examinations. New SEM applications based on the production of transmission electron microscopy-like (TEM-like) images are now possible with the recent introduction of new technologies such as low kV scanning transmission electron microscopy (STEM) detectors, automated scan generators and high-resolution column configurations capable of sub-nanometre resolution. Typical specimen types traditionally imaged by TEM have been examined including renal, lung, prostate and brain tissues. The specimen preparation workflow was unchanged from that routinely used to prepare TEM tissue, apart from replacing copper grids for section mounting with a silicon substrate. These instruments feature a small footprint with little in the way of ancillary equipment, such as water chillers, and are more cost-effective than traditional TEM columns. Also, a new generation of benchtop SEMs have recently become available and have also been assessed for its utility in the tissue pathology and cell biology settings.


Assuntos
Microscopia Eletrônica de Varredura/métodos , Neoplasias/diagnóstico , Neoplasias/patologia , Animais , Equipamentos para Diagnóstico , Humanos , Rim/patologia , Rim/ultraestrutura , Masculino , Camundongos , Próstata/patologia , Próstata/ultraestrutura
16.
Ren Fail ; 41(1): 1045-1053, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31809666

RESUMO

A 43-year-old Chinese man with a silicosis history was admitted to our hospital due to bilateral lower extremity edema for 1 year, exacerbating with hematuria for 2 months. He started working as a coal miner 30 years ago, and was diagnosed as silicosis 3 months ago. Lab tests revealed hematuria 3+, proteinuria 3+, and a serum creatinine value 2.47 mg/dl on routine check. He was diagnosed with focal proliferative IgA nephropathy (IgAN) and acute tubulo-interstitial nephritis by renal biopsy. He was treated with corticosteroids and got a remission 4 months later. Immunohistochemical staining showed the deposition of macrophage receptor with collagenous structure (MARCO), nod-like receptor pyrin domain-containing-3 (NLRP3), Caspase-1, apoptosis-associated speck (ASC), interleukin (IL)-1ß, and IL-18 in both glomerular and tubulo-interstitial areas. We proposed that the silicon exposure could be related to his kidney disease in the patient and NLRP3 mediated inflammation might be involved in its pathogenesis which needs further explorations.


Assuntos
Nefropatias/etiologia , Rim/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Silicose/complicações , Adulto , Humanos , Rim/ultraestrutura , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Silicose/metabolismo
17.
Int. j. morphol ; 37(4): 1335-1341, Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1040134

RESUMO

Food additives and flavour enhancers used in the food industry are potential health risks. We tested the hypothesis that the food additive and flavour enhancer, monosodium glutamate (MSG), which is the sodium salt of glutamic acid can induce ultrastructural alterations to the kidney, and the antioxidant vitamin E can protect against acute kidney injuries induced by a toxic dose of MSG in a rat model of the disease. The model group of rats received a daily dose of MSG (4 gm/kg) for 7 days, whereas the protective groups were either received a 100 mg/kg vitamin E plus MSG or 300 mg/kg vitamin E plus MSG for 7 days. Rats were then sacrificed on day 8. Transmission and light microscopy images revealed substantial kidney damage induced by MSG in the model group as demonstrated by degenerated epithelial cells with Pyknotic nuclei, swollen mitochondria, damaged brush margins, dilated tubules, and widening of Bowman's space with shrinkage and deformity of some glomeruli. Treatment of the model group with vitamin E showed a substantial protection of kidney tissue and renal ultrastructure by 300 mg/kg vitamin E compared to a partial protection by 100 mg/kg vitamin E. In addition, MSG significantly (p<0.05) increased serum levels of urea and creatinine, which were significantly (p<0.05) decreased with vitamin E. However, for serum creatinine, high doses of vitamin E (300 mg/kg) were more effective than lower doses (100 mg/kg) of vitamin E. These results indicate that vitamin E at 300 mg/kg effectively protects against MSG-induced acute kidney injury in rats.


Los aditivos alimentarios y los potenciadores del sabor utilizados en la industria alimentaria son riesgos potenciales para la salud. Probamos la hipótesis de que el aditivo alimentario y el potenciador del sabor, glutamato monosódico (MSG), la sal sódica del ácido glutámico, puede inducir alteraciones ultraestructurales del riñón, y que las propiedades antioxidantes de la vitamina E, pueden proteger contra las lesiones renales inducidas por una dosis tóxica de MSG en un modelo de rata. El grupo modelo de ratas recibió una dosis diaria de MSG (4 g / kg) durante 7 días, mientras que los grupos protectores recibieron una dosis de 100 mg / kg de vitamina E más MSG o 300 mg / kg de vitamina E más MSG durante 7 días. Las ratas se sacrificaron el día 8. Las imágenes de microscopía óptica y de transmisión revelaron un daño renal sustancial inducido por el MSG en el grupo modelo, como lo demuestran las células epiteliales degeneradas con núcleos picnóticos, mitocondrias hinchadas, bordes dañados, túbulos dilatados y ensanchamiento del espacio de Bowman, además de la deformidad de algunos glomérulos. El tratamiento del grupo modelo con vitamina E mostró una protección sustancial del tejido renal y la ultraestructura renal de 300 mg / kg de vitamina E en comparación con una protección parcial de 100 mg / kg de vitamina E. Además, el MSG aumentó significativamente (p <0,05) en el suero los niveles de urea y creatinina, disminuyeron significativamente (p <0,05) con la vitamina E. Sin embargo, para la creatinina sérica, las dosis altas de vitamina E (300 mg / kg) fueron más efectivas que las dosis más bajas (100 mg / kg) de vitamina E. Estos resultados indican que la vitamina E a 300 mg / kg protege eficazmente contra la lesión renal aguda inducida por MSG en ratas.


Assuntos
Animais , Ratos , Glutamato de Sódio/toxicidade , Vitamina E/uso terapêutico , Lesão Renal Aguda/tratamento farmacológico , Vitamina E/farmacologia , Ratos Sprague-Dawley , Microscopia Eletrônica de Transmissão , Modelos Animais de Doenças , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Rim/patologia , Rim/ultraestrutura
19.
Ann R Coll Surg Engl ; 101(8): 609-616, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508984

RESUMO

INTRODUCTION: Hypothermic machine perfusion, an organ preservation modality, involves flow of chilled preservation fluid through an allograft's vasculature. This study describes a simple, reproducible, human model that allows for interrogation of flow effects during ex vivo organ perfusion. MATERIALS AND METHODS: Gonadal veins from deceased human renal allografts were subjected to either static cold storage or hypothermic machine perfusion for up to 24 hours. Caspase-3, Krüppel-like factor 2 expression and electron microscopic analysis were compared between 'flow' and 'no-flow' conditions, with living donor gonadal vein sections serving as negative controls. RESULTS: The increase in caspase-3 expression was less pronounced for hypothermic machine-perfused veins compared with static cold storage (median-fold increase 1.2 vs 2.3; P < 0.05). Transmission electron microscopy provided ultrastructural corroboration of endothelial cell apoptosis in static cold storage conditions. For static cold storage preserved veins, Krüppel-like factor 2 expression diminished in a time-dependent manner between baseline and 12 hours (P < 0.05) but was abrogated and reversed by hypothermic machine perfusion (P < 0.05). CONCLUSIONS: Our methodology is a simple, reproducible and successful model of ex vivo perfusion in the context of human organ preservation. To demonstrate the model's utility, we establish that two widely used markers of endothelial health (caspase-3 and Krüppel-like factor 2) differ between the flow and no-flow conditions of the two predominant kidney preservation modalities. These findings suggest that ex vivo perfusion may mediate the induction of a biochemically favourable endothelial niche which may contribute tohypothermic machine perfusion's association with improved renal transplantation outcomes.


Assuntos
Transplante de Rim/métodos , Rim/irrigação sanguínea , Modelos Biológicos , Soluções para Preservação de Órgãos/farmacocinética , Preservação de Órgãos/métodos , Apoptose , Biomarcadores/metabolismo , Cadáver , Caspase 3/metabolismo , Temperatura Baixa , Endotélio Vascular/metabolismo , Humanos , Rim/metabolismo , Rim/ultraestrutura , Fatores de Transcrição Kruppel-Like/metabolismo , Microscopia Eletrônica , Perfusão/métodos , Veias/metabolismo , Veias/ultraestrutura
20.
Ann Diagn Pathol ; 43: 151403, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494491

RESUMO

Crystal-storing histiocytosis (CSH) is a rare manifestation of monoclonal gammopathy in which histiocytes containing monoclonal proteins in their cytoplasm are found in various organs of the body including the kidney. Within the kidney, these monoclonal crystal-laden histiocytes have been described to occur in the interstitium (most commonly) or in the glomerular mesangium. CSH within glomerular capillary loops has rarely been reported. We describe three cases of CSH primarily affecting the glomerular capillaries and review the literature of CSH in general. Twenty cases of CSH involving the kidney are present in the literature; three describe CSH in glomeruli, only one of which showed histiocytes predominantly in glomerular capillary loops, while 15 had predominantly or solely interstitial CSH. Most cases involve IgG kappa crystals with only one case involving lambda light chain. Patients with CSH predominantly involving the glomerular capillaries showed a trend toward lower serum creatinine and proteinuria at presentation, and several patients with CSH lacked a definitive diagnosis of a monoclonal gammopathy at the time of diagnosis, emphasizing the role that kidney biopsy and particularly electron microscopy play in diagnosis of this entity.


Assuntos
Mesângio Glomerular/patologia , Histiocitose/complicações , Rim/patologia , Adulto , Idoso , Biópsia , Creatinina/sangue , Feminino , Mesângio Glomerular/irrigação sanguínea , Mesângio Glomerular/metabolismo , Mesângio Glomerular/ultraestrutura , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Histiócitos/metabolismo , Histiócitos/patologia , Humanos , Rim/metabolismo , Rim/ultraestrutura , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/patologia , Masculino , Microscopia Eletrônica/métodos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Proteínas do Mieloma/metabolismo , Paraproteinemias/patologia , Proteinúria/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA