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1.
J Gastrointestin Liver Dis ; 29(3): 470, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32830825
2.
PLoS One ; 15(8): e0237503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810154

RESUMO

BACKGROUND: Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. METHODS: We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the effect of vasopressors infused at admission in the intensive care unit (ICU) and total intraoperative fluid balance. Our primary outcome was 48-hour acute kidney injury (AKI) and our secondary outcomes were 7-day AKI, need for postoperative renal replacement therapy (RRT), time to extubation in the ICU, time to ICU discharge and survival up to 1 year. We fitted models adjusted for confounders using generalized estimating equations or survival models using robust standard errors. We reported results with 95% confidence intervals. RESULTS: We included 532 patients. Vasopressors use was not associated with 48-hour or 7-day AKI but modified the effects of fluid balance on RRT and mortality. A higher fluid balance was associated with a higher need for RRT (OR = 1.52 [1.15, 2.01], p<0.001 for interaction) and lower survival (HR = 1.71 [1.26, 2.34], p<0.01 for interaction) only among patients without vasopressors. In patients with vasopressors, higher doses of vasopressors were associated with a higher mortality (HR = 1.29 [1.13, 1.49] per 10 µg/min of norepinephrine). CONCLUSION: The presence of any vasopressor at the end of surgery was not associated with AKI or RRT. The use of vasopressors might modify the harmful association between fluid balance and other postoperative outcomes. The liberal use of vasopressors to implement a restrictive fluid management strategy deserves further investigation.


Assuntos
Lesão Renal Aguda , Hemodinâmica/fisiologia , Cuidados Intraoperatórios/métodos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Adulto , Idoso , Estudos de Coortes , Feminino , Hidratação/métodos , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Quebeque/epidemiologia , Terapia de Substituição Renal/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento , Equilíbrio Hidroeletrolítico/fisiologia
3.
N Z Med J ; 133(1519): 12-23, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32777791

RESUMO

AIM: The objective of this research is to determine community dwelling patients' awareness of temporarily discontinuing medicines during acute illness, and the actions they would undertake when acutely unwell. METHOD: Adults taking long-term oral medicines for chronic health conditions completed a four-question self-completion paper-based questionnaire collecting data requiring quantitative analysis. Recruitment occurred in six participating Hawke's Bay community pharmacies during 2017 and 2018. RESULTS: One hundred and thirty people completed the survey. Seventeen (13%) recalled receiving guidance from a health professional on which medicines to stop during excessive vomiting or diarrhoea. Only three people, however, would stop their medicines. Eighteen percent (17/95) of participants aged 65 years and older were prescribed both a NSAID and either an angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin-II receptor blocker (ARB); five reported receiving advice to withhold medicines. Three participants were prescribed a Triple Whammy combination; none reported being advised to withhold medicines. CONCLUSION: A small proportion of the participants recalled receiving guidance to temporarily withhold medicines during acute illness; many indicated the advice would not be followed. The results indicate a degree of acute kidney injury prior (AKI) at-risk prescribing. There are opportunities to empower people to self-manage at-risk medicines during periods of acute illness.


Assuntos
Doença Aguda , Lesão Renal Aguda/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto/estatística & dados numéricos , Medicamentos sob Prescrição/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Fatores de Risco
4.
Life Sci ; 256: 118016, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603817

RESUMO

AIMS: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. MAIN METHODS: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 µg/kg, i.p.). KEY FINDINGS: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-α, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. SIGNIFICANCE: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.


Assuntos
Lesão Renal Aguda/prevenção & controle , Curcumina/farmacologia , Inflamação/prevenção & controle , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Curcumina/administração & dosagem , Inibidores de Lipoxigenase/administração & dosagem , Inibidores de Lipoxigenase/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Semaforina-3A/sangue , Semaforinas/metabolismo
5.
Yakugaku Zasshi ; 140(7): 929-936, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612058

RESUMO

Cisplatin therapy induces kidney injury as a side effect. Thus, replacement fluid must be administered to prevent kidney injury. In our hospital, we use a Gemcitabine and Cisplatin combination chemotherapy (GC) at a total volume of approximately 500 mL for biliary tract cancer. We investigated the safety of GC with a small amount of replacement fluid. As a result, no serious adverse events and renal injury occurred that required discontinuation of treatment. The median overall survival time was 260 d (95% confidence interval, 154-367 d). This study suggests that GC with a small amount of replacement fluid could be performed tolerability. But we need to be careful about choosing patients such as patients who can drink 1 L orally and patients who can be treated as outpatients.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Hidratação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Life Sci ; 257: 118004, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621918

RESUMO

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) often develop acute kidney injury (AKI) caused by myocardial ischemia reperfusion (MI/R), and this renal injury can be resolved notably by dexmedetomidine. Endoplasmic reticulum (ER) stress was reported to get involved in organ injury including AKI. OBJECTIVES: The current study aimed to address the correlation between MI/R induced AKI with ER stress and to assess the effects of dexmedetomidine pretreatment on AKI protection. METHOD: Patients selected for heart valve replacement surgery were randomly assigned to NS group (pre-anesthesia with 0.9% NaCl) and DEX group (pre-anesthesia with dexmedetomidine). Rat MI/R model was induced by occluding coronary artery for 30 min followed by 48-hour reperfusion. Rats were randomized into Sham (0.9% NaCl), I/R (MI/R + 0.9% NaCl) and I/R + DEX (MI/R + dexmedetomidine). Organ function and ER stress condition were evaluated by blood chemistry, pathology, and molecular test. RESULTS: Clinical data indicated dexmedetomidine pretreatment attenuated AKI and oxidative stress as well as postischemic myocardial injury in patients. Accordingly animal results suggested dexmedetomidine reduced cellular injury and improved postischemic myocardial and renal function. Dexmedetomidine also reduced myocardial and renal cells apoptosis and down-regulated ER stress. CONCLUSIONS: These results suggested that dexmedetomidine pretreatment attenuates MI/R injury-induced AKI by relieving the ER stress.


Assuntos
Dexmedetomidina/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/prevenção & controle , Idoso , Animais , Apoptose/efeitos dos fármacos , China , Dexmedetomidina/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Isquemia/metabolismo , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica/métodos , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
PLoS One ; 15(7): e0234921, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673348

RESUMO

BACKGROUND: Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well. METHODS: We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration ≥ 0.3 mg/dl from baseline to day 2-3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations. RESULTS: 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7-93.1] µg/mg vs. 19.9 [IQR 12.3-38.9] µg/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio <30 mg/g), the NGAL/creatinine ratio was 2.6 higher in CI-AKI vs. no CI-AKI (47.8 [IQR 11.8-75.3] vs. 18.6 [IQR 11.7-36.3] µg/mg). No significant differences were obtained for KIM-1 and calprotectin (p>0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60-0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 µg/mg has a negative predictive value of 96.5%. CONCLUSIONS: The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Biomarcadores/sangue , Angiografia Coronária/efeitos adversos , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria , Curva ROC , Insuficiência Renal Crônica/complicações
8.
Medicine (Baltimore) ; 99(22): e20330, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481407

RESUMO

The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ±â€Š23.1 to 87.3 ±â€Š21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ±â€Š32.2 to 85.5 ±â€Š85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Guanina/análogos & derivados , Antígenos E da Hepatite B/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Telbivudina/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/uso terapêutico , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Telbivudina/administração & dosagem , Telbivudina/efeitos adversos
9.
Leukemia ; 34(7): 1726-1729, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483300

RESUMO

The scientific community faces an unexpected and urgent challenge related to the SARS-CoV-2 pandemic and is investigating the role of receptors involved in entry of this virus into cells as well as pathomechanisms leading to a cytokine "storm," which in many cases ends in severe acute respiratory syndrome, fulminant myocarditis and kidney injury. An important question is if it may also damage hematopoietic stem progenitor cells?


Assuntos
Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Células-Tronco Hematopoéticas/virologia , Inflamassomos/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/prevenção & controle , Lesão Renal Aguda/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Furanos/farmacologia , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/genética , Miocardite/epidemiologia , Miocardite/imunologia , Miocardite/prevenção & controle , Miocardite/virologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Piroptose/efeitos dos fármacos , Piroptose/genética , Piroptose/imunologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Sulfonamidas/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/virologia
10.
Life Sci ; 257: 117918, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32525002

RESUMO

OBJECTIVE: To investigate protective efficacies and mechanisms of Cathelicidin-BF (BF-30) peptide on streptozotocin (STZ)-induced diabetic kidney injury. METHODS: Effects of BF-30 on hydrogen peroxide induced oxidative damage in HK-2 renal cells were assessed by CCK-8 method. Forty STZ-induced diabetic rats with kidney injury were randomly divided into model control group, BF-30 group at different doses (0.1, 0.3 and 0.9 mg/kg). Blood biochemical and kidney related indexes as well adrenal morphological changes, inflammation related markers of diabetic rats were measured. RESULTS: Cell viability of HK-2 cells with oxidative damage induced by hydrogen peroxide were significantly improved by BF-30 with 0.8 µg/mL for 56.5% and 1.6 µg/mL for 82.3% compared with control. Moreover, the decreased reactive oxygen species (ROS), and increased intracellular antioxidant enzymes GPX1, SOD2 and GSH were showed in BF-30 treated groups. In addition, co-incubation of BF-30 in HK-2 cells promoted the increase of p-AMPK and LC3, decreased activation of p-mTOR, BAX and Caspase 3. Chronic treatment of BF-30 improved the STZ-induced diabetic characteristics of diabetic kidney disease (DKD) model rats. Further renal histopathological examination revealed 12-week treatment of BF-30 effectively improved the morphology of nephropathy in DKD rats. Moreover, BF-30 also could ameliorate excessive oxidative stress, renal cell apoptosis and fibrosis, thereby protects renal tissues. CONCLUSION: BF-30 exerted protective effects on STZ-induced kidney injury mainly through the inhibiting oxidative stress in kidney tissue, reducing renal fibrosis, increasing autophagy, and reducing the renal cell apoptosis related proteins to decrease the cell damage and protect nephrocytes.


Assuntos
Lesão Renal Aguda/prevenção & controle , Catelicidinas/farmacologia , Rim/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Catelicidinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Feminino , Fibrose/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Rim/patologia , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina/farmacologia
12.
Int J Mol Sci ; 21(9)2020 May 05.
Artigo em Inglês | MEDLINE | ID: covidwho-175942

RESUMO

Coronaviruses (CoVs), including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the novel coronavirus disease-2 (SARS-CoV-2) are a group of enveloped RNA viruses that cause a severe respiratory infection which is associated with a high mortality [...].


Assuntos
Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/virologia , Pneumonia Viral/virologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/prevenção & controle , Angiotensina II/farmacologia , Catepsinas/metabolismo , Morte Celular/efeitos dos fármacos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Creatinina/sangue , Estado Terminal/mortalidade , Endossomos/efeitos dos fármacos , Endossomos/enzimologia , Endossomos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Incidência , Túbulos Renais Proximais/fisiopatologia , Lisossomos/efeitos dos fármacos , Lisossomos/enzimologia , Lisossomos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Receptores Virais/metabolismo , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/fisiopatologia , Internalização do Vírus , Replicação Viral
14.
Int J Mol Sci ; 21(9)2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32380787

RESUMO

Coronaviruses (CoVs), including Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and the novel coronavirus disease-2 (SARS-CoV-2) are a group of enveloped RNA viruses that cause a severe respiratory infection which is associated with a high mortality [...].


Assuntos
Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/virologia , Pneumonia Viral/virologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/prevenção & controle , Angiotensina II/farmacologia , Catepsinas/metabolismo , Morte Celular/efeitos dos fármacos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Creatinina/sangue , Estado Terminal/mortalidade , Endossomos/efeitos dos fármacos , Endossomos/enzimologia , Endossomos/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Incidência , Túbulos Renais Proximais/fisiopatologia , Lisossomos/efeitos dos fármacos , Lisossomos/enzimologia , Lisossomos/metabolismo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Receptores Virais/metabolismo , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/fisiopatologia , Internalização do Vírus , Replicação Viral
15.
Toxicology ; 440: 152487, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418911

RESUMO

Renal toxicity is the primary factor that limits clinical use of cisplatin (CP). A previous study showed that omeprazole (OME) protected against CP-induced toxicity in human renal tubular HK-2 cells and rat kidneys. However, the protective mechanisms of OME have not been characterized. We evaluated the ability of OME to inhibit CP-induced inflammation, and characterized the pathways responsible for this effect. Rats were randomly divided into five groups (n = 10/group). The OME groups were intraperitoneally injected with 1.8 or 3.6 mg OME /kg body weight once daily for 5 days. One hour after final administration of vehicle or OME, all rats (except those in control group and OME alone group) were intraperitoneally injected with 15 mg/kg CP. Twenty-four hours after CP injection, the surgery was applied. The time points and dosing of OME and CP were calculated based on previous studies and the therapeutic dose for patients. Omeprazole attenuated CP-induced apoptosis and damage in vivo and in vitro, as evidenced by increased cell viability and prevention of structural damage. Omeprazole ameliorated CP-induced renal injury through inhibition of NF-κB activation and IκBα degradation, and down-regulation of toll-like receptor 4 (TLR4) and Nod-like receptor protein 3 (NLRP3). Lipopolysaccharide, a TLR4 agonist, was used to verify this mechanism. The results indicated that OME inhibited CP-induced expression of inflammatory proteins, and this effect was blunted by co-treatment with LPS in HK-2 cells. These findings suggested that the protective effects of OME against CP-induced kidney damage may occur through inhibition of the TLR4/NF-κB/NLRP3 signaling pathway. This study provided evidence that OME may be a promising agent to inhibit CP-induced nephrotoxicity.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Antineoplásicos , Cisplatino , NF-kappa B/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Proteínas I-kappa B/efeitos dos fármacos , Testes de Função Renal , Masculino , Ratos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
16.
Life Sci ; 255: 117719, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428599

RESUMO

AIMS: To investigate the protective function of exosomes from adipose tissue-derived mesenchymal stem cells (AMSCs) in sepsis-induced acute kidney injury (AKI) in mice and the possible underlying mechanism in order to provide a theoretical and experimental basis for using exosomes in clinical. MAIN METHODS: The AKI model was prepared through cecal ligation and puncture (CLP). Exosomes were injected via the tail vein of mice. Male C57/BL6 mice (18-22 g; 6-8 weeks old) were randomly grouped. Firstly, after mice were modeled, the variations of inflammatory cytokines and kidney functions at different time points (0, 6, 12, 24 and 48 h) were comprehended. Secondly, mice were divided into Sham, CLP and CLP + Exo, and the survival rates of each group were observed. Lastly, a time point (24 h) was selected for exploring the effect and mechanism of exosomes. The levels of inflammatory cytokines in serum were detected by ELISA, while the kidney was by immunohistochemistry. Kidney histopathological score were analyzed by hematoxylin-eosin (HE) staining. The protein levels of sirtuin 1 (SIRT1), inflammation-related and apoptosis-related were detected by western blot. KEY FINDINGS: In CLP group, renal function gradually deteriorated, and the kidneys was in a state of inflammation, apoptosis and microcirculation disorders. However, SIRT1 was activated after intervention of exosomes in CLP mice, which reversed above changes. The mortality was reduced with treatment of exosomes in AKI mice. SIGNIFICANCE: In mice of sepsis-induce AKI, the intervention of AMSCs derived exosomes played a renal protective effect. The mechanism may be through SIRT1 signaling pathway.


Assuntos
Lesão Renal Aguda/prevenção & controle , Exossomos/metabolismo , Células-Tronco Mesenquimais/citologia , Sepse/terapia , Sirtuína 1/metabolismo , Lesão Renal Aguda/etiologia , Tecido Adiposo/citologia , Animais , Apoptose/fisiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/complicações
17.
J Pharmacol Sci ; 143(3): 226-233, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32446726

RESUMO

Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), characterized by tubulointerstitial inflammation. Currently, progress in developing effective therapies to prevent or ameliorate AKI by anti-inflammation remains slow. Emerging studies have suggested that NLRP3 (the NOD-, LRR- and pyrin domain-containing 3) inflammasome plays a key role in a wide spectrum of kidney disease models including I/R injury. In this study, we investigated the renal protective effects of A68930, a specific agonist for the D-1 dopamine receptor (DRD1), which was recently recognized to downregulate NLRP3 inflammasome via DRD1 signaling. AKI was induced by renal I/R injury and A68930 was intraperitoneally injected 3 times after renal reperfusion. We showed that A68930 significantly ameliorated renal dysfunction. Meanwhile, A68930 markedly reduced macrophages and T cells infiltration, renal pro-inflammatory cytokines production (TNF-α, IL-6, IL-1ß), serum pro-inflammatory cytokine (TNF-α and IL-6) and NLRP3 inflammasome activation. Additionally, A68930 attenuated I/R-induced mitochondria injury, which was observed by transmission electron microscopy. In summary, our results demonstrated that activation of DRD1 by A68930 inhibited renal and systematic inflammation, and improved kidney function in I/R induced AKI model, which was probably related to the inhibition of the NLRP3 inflammasome activation.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/genética , Cromanos/farmacologia , Cromanos/uso terapêutico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/metabolismo , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/complicações , Fator de Necrose Tumoral alfa/metabolismo
18.
Londres; National Institute for Health and Care Excellence; Mayo 6, 2020. 15 p.
Monografia em Inglês | BIGG | ID: biblio-1097056

RESUMO

The purpose of this guideline is to help healthcare professionals prevent, detect and manage acute kidney injury in adults in hospital with known or suspected COVID-19. This is important to improve outcomes and reduce the need for renal replacement therapy.


Assuntos
Humanos , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/complicações , Infecções por Coronavirus/prevenção & controle , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/prevenção & controle , Lesão Renal Aguda/terapia , Betacoronavirus
19.
Am J Physiol Renal Physiol ; 318(6): F1531-F1538, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390514

RESUMO

Renal ischemia-reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of chromobox 7 (CBX7) could attenuate renal I/R injury in vivo and in vitro as well as the potential mechanisms. Adult male mice were subjected to right renal ischemia and reperfusion for different periods, both with and without the CBX7 inhibitor UNC3866. In addition, human kidney cells (HK-2) were subjected to a hypoxia/reoxygenation (H/R) process for different periods, both with or without the CBX7 inhibitor or siRNA for CBX7. The results showed that expression of CBX7, glucose regulator protein-78 (GRP78), phosphorylated eukaryotic translation initiation factor-2α (p-eIF2α), and C/EBP homologous protein (CHOP) were increased after extension of I/R and H/R periods. Moreover, overexpression of CBX7 could elevate the expression of CBX7, GRP78, p-eIF2α, and CHOP. However, CBX7 inhibition with either UNC3866 or genetic knockdown led to reduced expression of GRP78, p-eIF2α, and CHOP through nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 activation in I/R and H/R injury. Furthermore, ML385, the Nrf2 inhibitor, could elevate endoplasmic reticulum stress levels, abrogating the protective effects of UNC3866 against renal I/R injury. In conclusion, our results demonstrated that CBX7 inhibition alleviated acute kidney injury by preventing endoplasmic reticulum stress via the Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury.


Assuntos
Lesão Renal Aguda/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Rim/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oligopeptídeos/farmacologia , Complexo Repressor Polycomb 1/antagonistas & inibidores , Traumatismo por Reperfusão/prevenção & controle , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Animais , Hipóxia Celular , Linhagem Celular , Heme Oxigenase-1/genética , Humanos , Rim/enzimologia , Rim/patologia , Masculino , Proteínas de Membrana/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais
20.
AJR Am J Roentgenol ; 215(1): 15-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32348183

RESUMO

OBJECTIVE. The purpose of this study was to determine whether contrast medium volume and method of administration and baseline estimated glomerular filtration rate influence the efficacy of prophylactic hydration for prevention of acute kidney injury after contrast administration. MATERIALS AND METHODS. An online search of PubMed conducted on August 25, 2017, produced a total of 697 studies. After the reports were reviewed, nine were included in this study. The extracted data on all patients in these studies were separated into a group that received prophylactic hydration and a group that did not. The following three parameters were used for subgroup analysis: contrast medium volume, contrast administration method, and baseline estimated glomerular filtration rate. The t test was performed, and study-level odds ratios with 95% CIs and p values were calculated. Tests of heterogeneity were conducted. RESULTS. When the volume of contrast agent administered exceeded 100 mL, hydration was beneficial in the prevention of contrast-induced acute kidney injury (odds ratio, 0.546). If the volume was less than 100 mL, hydration had no efficacy in preventing contrast-induced acute kidney injury (odds ratio, 0.917). Administration route and baseline estimated glomerular filtration rate exerted no effect on the efficacy of prophylactic hydration. CONCLUSION. For patients who receive less than 100 mL of contrast medium, the prevalent practice for contrast-enhanced CT studies, prophylactic hydration may not be necessary, regardless of the estimated glomerular filtration rate or route of contrast administration. For patients undergoing procedures requiring administration of large volumes of contrast medium, however, hydration is recommended to prevent contrast-induced acute kidney injury.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Hidratação/métodos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos
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