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1.
N Engl J Med ; 382(5): 416-426, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-31995687

RESUMO

BACKGROUND: Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models to identify mechanisms by which suPAR acts and to assess it as a therapeutic target. METHODS: We measured plasma levels of suPAR preprocedurally in patients who underwent coronary angiography and patients who underwent cardiac surgery and at the time of admission to the intensive care unit in critically ill patients. We assessed the risk of acute kidney injury at 7 days as the primary outcome and acute kidney injury or death at 90 days as a secondary outcome, according to quartile of suPAR level. In experimental studies, we used a monoclonal antibody to urokinase plasminogen activator receptor (uPAR) as a therapeutic strategy to attenuate acute kidney injury in transgenic mice receiving contrast material. We also assessed cellular bioenergetics and generation of reactive oxygen species in human kidney proximal tubular (HK-2) cells that were exposed to recombinant suPAR. RESULTS: The suPAR level was assessed in 3827 patients who were undergoing coronary angiography, 250 who were undergoing cardiac surgery, and 692 who were critically ill. Acute kidney injury developed in 318 patients (8%) who had undergone coronary angiography. The highest suPAR quartile (vs. the lowest) had an adjusted odds ratio of 2.66 (95% confidence interval [CI], 1.77 to 3.99) for acute kidney injury and 2.29 (95% CI, 1.71 to 3.06) for acute kidney injury or death at 90 days. Findings were similar in the surgical and critically ill cohorts. The suPAR-overexpressing mice that were given contrast material had greater functional and histologic evidence of acute kidney injury than wild-type mice. The suPAR-treated HK-2 cells showed heightened energetic demand and mitochondrial superoxide generation. Pretreatment with a uPAR monoclonal antibody attenuated kidney injury in suPAR-overexpressing mice and normalized bioenergetic changes in HK-2 cells. CONCLUSIONS: High suPAR levels were associated with acute kidney injury in various clinical and experimental contexts. (Funded by the National Institutes of Health and others.).


Assuntos
Lesão Renal Aguda/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Angiografia Coronária/efeitos adversos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Idoso , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Biomarcadores/sangue , Estado Terminal , Modelos Animais de Doenças , Feminino , Humanos , Unidades de Terapia Intensiva , Túbulos Renais/citologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Razão de Chances , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Medição de Risco/métodos , Ativador de Plasminogênio Tipo Uroquinase/farmacologia
2.
Toxicol Lett ; 318: 65-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654803

RESUMO

OBJECTIVE: The optimal measuring timing of serum/plasma Cystatin C (CysC) for early detection of contrast-induced acute kidney injury (CIAKI) remains un-studied. We elucidated further on this issue. METHODS: We searched PubMed, MEDLINE, and Embase from inception until March 2018 for studies evaluating diagnostic accuracy of CysC for detecting CIAKI in patients exposed to contrast agents during diagnostic examinations or cardiac/peripheral catheterizations. RESULTS: A total of 10 relevant studies, comprising 2554 patients, were included and divided into the <24 -h and 24 -h groups based on CysC measuring timing (i.e., hours after contrast agent exposure). Compared with creatinine, pooled diagnostic odds ratio of CysC for detecting CIAKI of the <24 -h and 24 -h groups was 7.59 (95 % confidence interval [CI]: 1.31-44.08) and 53.81 (95 % CI: 13.57-213.26). Pooled sensitivity of the <24 -h and 24 -h groups was 0.81 and 0.88. Pooled specificity of the <24 -h and 24 -h groups was 0.64 and 0.88, respectively. Area under the hierarchical summary receiver operating characteristic curve of the <24 -h and 24 -h groups was 0.75 and 0.93. CONCLUSIONS: Measuring CysC at 24 h after contrast agent exposure shows higher diagnostic accuracy for early detection of CIAKI than measuring CysC at <24 h after contrast agent exposure.


Assuntos
Lesão Renal Aguda/diagnóstico , Meios de Contraste/efeitos adversos , Cistatina C/sangue , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Idoso , Biomarcadores/sangue , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo
3.
Medicina (B Aires) ; 79(5): 391-396, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31671389

RESUMO

High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.


Assuntos
Transtornos Nutricionais/sangue , Transtornos Nutricionais/etiologia , Vitamina B 12/sangue , Lesão Renal Aguda/sangue , Lesão Renal Aguda/complicações , Doenças Hematológicas/sangue , Doenças Hematológicas/complicações , Humanos , Hepatopatias/sangue , Hepatopatias/complicações , Neoplasias/sangue , Neoplasias/complicações , Vitamina B 12/efeitos adversos
4.
Clin Interv Aging ; 14: 1763-1769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695346

RESUMO

Background: Critically ill older patients with acute kidney injury (AKI), also referred to as acute renal failure, are associated with high in-hospital mortalities. Preexisting malnutrition is highly prevalent among AKI patients and increases in-hospital mortality rate. This study is to evaluate the predictive power of some serum nutritional related biomarkers predicting the 90 days in-hospital mortality of critically ill older patients with AKI. Methods: A prospective, observational study was conducted in a university teaching hospital. One hundred and five critically ill older patients with AKI aged 60-95 were enrolled and were divided into survival group (n=44) and non-survival group (n=61) in the light of their final outcomes. Receiver operating characteristic analyses (ROC) were performed to calculate the area under ROC curve (AUC). Sensitivity and specificity of in-hospital mortality prediction were calculated. Results: Significant differences were found between the survival group and non-survival group of critically ill older patients with AKI. AUC of low density lipoprotein (LDL) and albumin were 0.686 and 0.595, respectively. The asymptotic 95% confidence intervals of LDL and albumin were 0.524-0.820 and 0.488-0.696, respectively. Sensitivity of the 90 days in-hospital mortality prediction of LDL and albumin were 68.71% and 69.09%, respectively. Specificity of 90 days in-hospital mortality prediction of LDL and albumin were 69.23% and 50.0%, respectively. Conclusion: LDL and albumin did not have sufficient power to predict the 90 days in-hospital mortality of critically ill older patients with AKI. Further research on the association between malnutrition and poor prognosis of critically ill older patients with AKI is needed in the future.Trial registration: ClinicalTrials.gov identifier: NCT00953992.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Mortalidade Hospitalar , Lipoproteínas LDL/sangue , Albumina Sérica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
5.
Medicine (Baltimore) ; 98(43): e16989, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651833

RESUMO

Periprocedural myocardial injury (PMI) and contrast-induced nephropathy (CIN) are frequent complications of percutaneous coronary intervention (PCI) associated with early and late major adverse cardiovascular events. Both conditions are associated with similar risk factors, which could imply their possible association. The aim of our study was to assess the correlation of PMI and early postprocedural creatinine shift (ECS) as a marker of renal injury.A total of 209 hospitalized patients with stable coronary artery disease (CAD) were enrolled, who underwent an elective PCI in a period of 12 months. All patients had their serum high-sensitivity troponin I (hsTnI) measured at baseline and 16 hours after the PCI. PMI was defined according to the elevation of postprocedural hsTnI using criteria provided by both the most recent consensus documents as well as evidence-based data. Renal injury was evaluated using the ECS concept. Serum creatinine (SCr) was also measured at baseline and at 16 hours. ECS was defined as SCr >5% at 16 hours compared to baseline.Although incidence of both PMI (77.5%) and ECS (44.5%) were high, no association of these 2 conditions could be found. Further analyses of our data showed that diabetes is associated with a higher incidence of ECS, while patients on beta-blocker therapy had a lower incidence of ECS.In our study, no association between PMI and ECS was found. Additional studies with a larger number of patients and longer patient observation are needed to assess the correlation between PMI and CIN as well as to validate the attractive, but controversial, concept of ECS as an early marker of CIN.


Assuntos
Lesão Renal Aguda/epidemiologia , Meios de Contraste/efeitos adversos , Traumatismos Cardíacos/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/cirurgia , Creatinina/sangue , Estudos Transversais , Procedimentos Cirúrgicos Eletivos , Feminino , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Fatores de Risco , Troponina I/sangue
6.
BMC Res Notes ; 12(1): 484, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383003

RESUMO

OBJECTIVE: This study aimed to determine if contrast medium volume (CMV) is a risk factor for acute kidney injury (AKI) during transcatheter aortic valve implantation (TAVI) via a transfemoral approach performed without major complications. All TAVI procedures performed at our institution between March 2014 and March 2018 were retrospectively reviewed. AKI was diagnosed using the Acute Kidney Injury Network classification based on the Valve Academic Research Consortium-2 definition. Procedures performed via a transapical approach and those in which circulatory dynamics failed intraoperatively were excluded. RESULTS: Eighty-one (96.4%) of 100 patients scheduled for TAVI were enrolled; seven (8.6%) developed AKI and 74 (91.4%) did not. The serum creatinine (SCr) level was significantly higher (p < 0.05) and the estimated glomerular filtration rate was significantly lower in the AKI group (p < 0.05). The CMV was significantly higher in the AKI group (103 ml vs 84 ml, p < 0.05), as was the CMV × SCr/BW value (3.34 vs 1.49, p < 0.01). The area under the curve for CMV × SCr/BW was 0.9228 and the cut-off value was 2.99. The CMV, SCr, and estimated glomerular filtration rate affect the likelihood of AKI after transfemoral TAVI and a CMV × SCr/BW value > 2.99 accurately predicts AKI.


Assuntos
Lesão Renal Aguda/diagnóstico , Meios de Contraste/metabolismo , Creatinina/sangue , Implante de Prótese de Valva Cardíaca/métodos , Substituição da Valva Aórtica Transcateter/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/fisiopatologia , Idoso de 80 Anos ou mais , Feminino , Taxa de Filtração Glomerular , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Humanos , Período Intraoperatório , Modelos Logísticos , Masculino , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/estatística & dados numéricos
7.
Ann Biol Clin (Paris) ; 77(4): 375-380, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418698

RESUMO

Blood concentration of cystatin C is independent of muscle mass and tubular secretion. It can be used, in the absence of a reference method, as an alternative marker to creatinine for the evaluation of renal function and the estimation of glomerular filtration rate (GFR). Both particle-enhanced immunonephelemetry (PENIA) or immunoturbidimetry (PETIA) methods are available to determine cystatin C. From an analytical point of view, it is recommended to use methods whose calibration is traceable to the reference material (ERM-DA471/IFCC) and to report an estimated GFR based on cystatin C. The main equations used are those developed in 2012 by the group "Chronic kidney disease epidemiology collaboration (CKD-EPI)" for adults and those published by Schwartz in 2012 for children. National and international recommendations suggest using a cystatin C-based GFR estimate as a confirmatory test in the clinical settings where the relationship between creatinine production and muscular mass impairs the clinical performance of creatinine. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the estimation and/or the monitoring of renal function in children and adolescents due to rapid changes in muscle mass; in patients with impaired muscle mass and in patients with an alteration of tubular secretion of creatinine (essentially iatrogenic effects).


Assuntos
Cistatina C/análise , Taxa de Filtração Glomerular , Testes de Função Renal/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Criança , Creatinina/sangue , Cistatina C/sangue , Humanos , Testes de Função Renal/normas , Padrões de Referência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Estatística como Assunto/métodos , Estatística como Assunto/normas
8.
Am J Health Syst Pharm ; 76(16): 1204-1210, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369115

RESUMO

PURPOSE: Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal ß-lactams (APBLs) are reported. METHODS: A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset. RESULTS: A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734). CONCLUSION: Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.


Assuntos
Lesão Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Sepse/tratamento farmacológico , Vancomicina/efeitos adversos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Antibacterianos/administração & dosagem , Criança , Creatinina/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Combinação Piperacilina e Tazobactam/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Vancomicina/administração & dosagem
9.
Int J Mol Sci ; 20(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366007

RESUMO

Acute kidney injury (AKI) is a serious complication of acute pancreatitis (AP), which occurs in up to 70% of patients with severe AP and significantly increases the risk of mortality. At present, AKI is diagnosed based on dynamic increase in serum creatinine and decreased urine output; however, there is a need for earlier and more accurate biomarkers. The aim of the study was to review current evidence on the laboratory tests that were studied as the potential biomarkers of AKI in AP. We also briefly summarized the knowledge coming from the studies including sepsis or ICU patients since severe acute pancreatitis is associated with systemic inflammation and organ failure. Serum cystatin C and serum or urine NGAL have been shown to predict or diagnose AKI in AP; however, this evidence come from the single center studies of low number of patients. Other markers, such as urinary kidney injury molecule-1, cell cycle arrest biomarkers (tissue inhibitor metalloproteinase-2 and urine insulin-like growth factor-binding protein 7), interleukin-18, liver-type fatty acid-binding protein, or calprotectin have been studied in other populations suffering from systemic inflammatory states. In AP, the potential markers of AKI may be significantly influenced by either dehydration or inflammation, and the impact of these factors may be difficult to distinguish from kidney injury. The subject of AKI complicating AP is understudied. More studies are needed, for both exploratory (to choose the best markers) and clinical (to evaluate the diagnostic accuracy of the chosen markers in real clinical settings).


Assuntos
Lesão Renal Aguda/sangue , Pancreatite/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Cistatina C/sangue , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Lipocalina-2/sangue , Lipocalina-2/urina , Pancreatite/complicações , Pancreatite/urina , Inibidor Tecidual de Metaloproteinase-2/sangue
10.
J Vet Intern Med ; 33(5): 2029-2036, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381195

RESUMO

BACKGROUND: Bleeding tendencies can occur with uremia. OBJECTIVES: To characterize primary hemostatic function in dogs with acute kidney injury (AKI). ANIMALS: Ten dogs with International Renal Interest Society AKI grade III or above and 10 healthy controls. METHODS: Prospective study comparing PCV, platelet count, platelet aggregometry (Multiplate), and von Willebrand factor antigen to collagen binding activity ratio (vWF:Ag:vWF:CBA) in 2 groups of dogs (AKI group versus controls). Buccal mucosal bleeding time was measured in the AKI group only. Data are presented as median [25th, 75th percentile] unless otherwise stated. Significance was set at P < .05. RESULTS: Mean PCV was significantly lower in the AKI (34.7%; ±SD, 8.8) than in the control (46.1%; ±SD, 3.6; P < .001) group. Platelet count was significantly higher in the AKI (350.5 × 103 /µL [301, 516]) than in the control (241 × 103 /µL [227, 251]; P = .01) group. Collagen-activated platelet aggregometry measured as area under the curve was significantly lower in the AKI (36.9 ± 17.7) than in the control (54.9 ± 11.2; P = .05) group. vWF:Ag:vWF:CBA was significantly higher in the AKI (2.2 [1.9, 2.6]) than in the control (1.1 [1.1, 1.2]; P = .01) group. There was a strong correlation between vWF:Ag:vWF:CBA and creatinine (r = 0.859; P < .001), but no other variables. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with AKI had decreased collagen-activated platelet aggregation and appear to have a type II von Willebrand disease-like phenotype as indicated by the high vWF:Ag:vWF:CBA.


Assuntos
Lesão Renal Aguda/veterinária , Colágeno/metabolismo , Doenças do Cão/fisiopatologia , Fator de von Willebrand/análise , Lesão Renal Aguda/sangue , Lesão Renal Aguda/fisiopatologia , Animais , Tempo de Sangramento/veterinária , Doenças do Cão/sangue , Cães , Feminino , Masculino , Mucosa Bucal , Contagem de Plaquetas/veterinária , Testes de Função Plaquetária/veterinária , Estudos Prospectivos
11.
S Afr J Surg ; 57(2): 63, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31342688

RESUMO

BACKGROUND: Crush injury is a common presenting clinical problem in South African trauma patients, causing acute kidney injury (AKI). It has been theorised previously that the AKI was not due to an anaerobic phenomenon. A previous local study noted the presence of a mild hyperlactataemia among patients with crush syndrome, but the significance and causes of this was not fully explored. This study aimed to examine the incidence of hyperlactataemia in patients with crush syndrome presenting to a busy emergency department (ED) in rural South Africa. METHOD: The study was conducted at Edendale Hospital in KwaZulu-Natal province in South Africa from 1 June 2016 to 31 December 2017. All patients from the ED who had sustained a crush injury secondary to a mob assault were included in the study. Patients with GCS on arrival of < 13 or polytrauma were excluded from analysis. The primary outcome of interest was the presence of hyperlactataemia (> 2.0mmol/L) on presentation. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose and stage AKI as a secondary outcome. RESULTS: A total of 84 patients were eligible for analysis. Sixty-nine (82%) patients presented with hyperlactataemia. The median serum lactate was 4.9mmol/L (IQR 2.3-7.2mmol/L). Fifteen (18%) patients were diagnosed with AKI on presentation according to serum creatinine. Ten patients were diagnosed as Stage 1, three were Stage 2 and two Stage 3 AKI respectively. There was no difference in the incidence of AKI in patients with or without hyperlactataemia (p = 0.428). Time from injury to presentation was a median 365 minutes (IQR 180-750 minutes). Six (7%) patients were admitted to high care unit and nine (11%) were admitted to the intensive care unit (ICU). No patients died within 48 hours of admission. Two patients received renal replacement therapy during the first 48 hours of admission to hospital. CONCLUSION: Hyperlactataemia is a common feature of patients presenting to the ED following crush syndrome secondary to beatings received during interpersonal violence. The origin of this hyperlactataemia is currently unknown. Further research needs to be conducted into the origin of the hyperlactataemia and its clinical significance. In this cohort, the utilisation of RRT was low but the incidence of AKI was high and developed rapidly following the injury. The utilisation of RRT also needs to be further studied in larger patient populations in South Africa to make local clinical recommendations for use.


Assuntos
Lesão Renal Aguda/sangue , Vítimas de Crime , Lesões por Esmagamento/sangue , Hiperlactatemia/sangue , Lesão Renal Aguda/terapia , Adulto , Lesões por Esmagamento/terapia , Feminino , Humanos , Hiperlactatemia/terapia , Masculino , Fatores de Risco , África do Sul/epidemiologia , Síndrome
12.
Biomed Res Int ; 2019: 7298635, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31346523

RESUMO

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major and serious complication in patients undergoing cardiac surgery and is independently associated with perioperative mortality and mortality. Therapeutic intervention aiming at reversing kidney dysfunction seems disappointing across multiple settings. Consequently, attention has shifted from treatment to prevention and early detection. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have unified diagnostic standards mainly based on the serum creatinine (Scr) level or urine output, but neither marker is kidney specific. Efforts have been made to identify novel biomarkers with high sensitivity and specificity. The diagnostic capabilities of neutrophil gelatinase-associated lipocalin (NGAL) and G1 cell cycle arrest biomarker as biomarkers have been confirmed in a large number of clinical trials. The utility of biomarkers of cardiac function and inflammation has been validated in clinical studies. Aiming to offer valuable information for further research, we summarize the progress in defining current markers relevant to CSA-AKI in the last three years.


Assuntos
Lesão Renal Aguda/sangue , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Lipocalina-2/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Proteínas da Fase Aguda/metabolismo , Creatinina/sangue , Diagnóstico Precoce , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Humanos , Rim/metabolismo , Rim/patologia
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(2): 224-229, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31309763

RESUMO

Cardiac surgery-related acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery in adults. Currently, there is no specific examination method, and the diagnosis relying on serum creatinine and urine volume changes is of hysteresis. Biomarkers with the potential to predict CSA-AKI have become the focus in recent years. Clinical studies have shown that neutrophil gelatinase related lipid transporters and cell cycle inhibitors are of high diagnostic value; liver fatty acid binding protein can be used to assist in the diagnosis of CSA-AKI; microRNAs help to assess the poor prognosis of patients; the combined application of biomarkers may be used to predict the occurrence of CSA-AKI. CSA-AKI biomarkers provide the possibility for early clinical diagnosis and timely intervention, and are expected to become a new breakthrough in the diagnosis and treatment of CSA-AKI.


Assuntos
Lesão Renal Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina/sangue , Humanos
14.
Biosens Bioelectron ; 142: 111482, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31279172

RESUMO

In this study, we demonstrate a novel affinity peptide-incorporated electrochemical biosensor for the detection of acute kidney injury and the diabetic biomarker neutrophil gelatinase-associated lipocalin (NGAL). Biopanning of the M13 phage display library over immobilized NGAL led to the rapid identification of unique affinity peptide with an amino acid sequence of DRWVARDPASIF, and the peptide-displayed phage particles were found to be specific affinities for NGAL. To address the development of peptide-based electrochemical sensor, a series of synthetic peptides away from phage particles was rationally designed, chemically synthesized, and immobilized to a gold sensor layer. Among five synthetic peptide derivatives tested, NGAL BP1 was selected as most promising recognition receptor, and its binding affinity was monitored by SWV and EIS. Using EIS, the limit of detection (LOD) was 1.74 ng/mL, while SWV had a LOD of 3.93 ng/mL. The detection performance of the peptide-incorporated sensor was comparable to commercially available ELISA NGAL detection kits. In addition, the validation of the peptide sensor was also confirmed with plasma from patients, and it was observed that the sensitivity of the peptide sensor showed a statistically significant difference. Our results show that the phage and peptide sensor system could detect NGAL with high sensitivity and selectivity, and this suggests its potential use as a biosensing platform for monitoring NGAL in a miniaturized electrochemical biosensor.


Assuntos
Técnicas Biossensoriais/métodos , Lipocalina-2/sangue , Peptídeos/química , Lesão Renal Aguda/sangue , Sequência de Aminoácidos , Sítios de Ligação , Biomarcadores/sangue , Técnicas Eletroquímicas/métodos , Ouro/química , Humanos , Limite de Detecção , Lipocalina-2/análise , Biblioteca de Peptídeos
15.
PLoS Negl Trop Dis ; 13(7): e0007486, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260445

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). CONCLUSIONS/SIGNIFICANCE: AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Mordeduras de Serpentes/complicações , Venenos de Víboras/sangue , Venenos de Víboras/urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Adolescente , Adulto , Idoso , Animais , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Víbora de Russell , Fatores de Tempo , Adulto Jovem
16.
Tohoku J Exp Med ; 248(2): 63-71, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31178527

RESUMO

Oxidative stress (OS) frequently contributes to the development of acute kidney injury (AKI). Iron can promote oxidative stress and tissue injury by catalyzing free reactive oxygen species (ROS) generation and increasing the steady-state concentration of these potent oxidants. The anticipated role of ferritin is to protect from OS by sequestering iron and limiting its involvement in reactions that generate ROS. In this prospective study, we aimed to investigate the association between serum ferritin levels and kidney function recovery among patients with AKI. Renal recovery was determined as a return of serum creatinine to less than 1.25 times the baseline value after 90 days of follow-up. One hundred twelve patients (72 males and 40 females, 63.68 ± 10.6 years old) were included in the final analysis. They were divided into AKI recovery (n = 76) and non-recovery groups (n = 36). Ferritin levels on admission were higher in AKI recovery group [284 (IQR 153-525) ng/mL] compared with the non-recovery group [127.4 (IQR 30-243) ng/mL], p < 0.001. Serum ferritin levels and the renal recovery significantly positively correlated (r = 0.72, p < 0.001). In multiple linear regression analysis, higher serum ferritin was associated with renal function recovery (OR 3.68, CI 2.02-3.97, p < 0.001). The optimal cut-off point of 240.5 ng/mL was determined for serum ferritin, which showed a sensitivity of 75.8% and a positive predictive value of 90%. In conclusion, serum ferritin levels on admission may be used as a prognostic marker for predicting renal recovery in AKI patients.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/fisiopatologia , Ferritinas/sangue , Testes de Função Renal , Recuperação de Função Fisiológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ferro/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC
17.
Dis Markers ; 2019: 8480925, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191757

RESUMO

Purpose: To analyse the capacity of whole-blood NGAL (wbNGAL) to stratify AKI in critically ill patients with and without sepsis. Methods: Whole-blood NGAL was measured with a point-of-care device at admission and 48 hours later in patients admitted to a general ICU. Patients were classified by the AKIN and KDIGO classifications at admission and 24 and 48 hours. We performed an ROC curve analysis. wbNGAL values at admission were compared in patients with sepsis and septic shock. Results: The study included 100 consecutively admitted patients (40 female) with mean age 59.1 ± 17.8 years. Thirty-three patients presented AKI at admission, and 10 more developed it in the next 48 h. Eighteen patients had AKI stage 3, 14 of them at admission. Nine patients required renal replacement therapy. According to KDIGO at admission, wbNGAL values were 78 µg/L (60-187) in stage 0 (n = 67), 263 µg/L (89-314) in stage 1 (n = 8), 484 µg/L (333-708) in stage 2 (n = 11), and 623 µg/L (231-911) in stage 3 (n = 14), p = 0.0001 for trend. Ten patients did not complete 48 hours of study: 6 of 10 were discharged (initial wbNGAL 130 µg/L (60-514)) and 4 died (773 µg/L (311-1010)). The AUROC curve of wbNGAL to predict AKI was 0.838 (95% confidence interval 0.76-0.92, p = 0.0001), with optimal cut-off value of 178 µg/L (sensitivity 76.7%, specificity 78.9%, p < 0.0001). At admission, twenty-nine patients had sepsis, of whom 20 were in septic shock. wbNGAL concentrations were 81 µg/L (60-187) in patients without sepsis, 481 (247-687) in those with sepsis, and 623.5 µg/L (361-798) in the subgroup of septic shock (p < 0.0001). Conclusions: Whole-blood NGAL concentration at ICU admission was a good stratifier of AKI in critically ill patients. However, wbNGAL concentrations were higher in septic patients irrespective of AKI occurrence.


Assuntos
Lesão Renal Aguda/sangue , Lipocalina-2/sangue , Lesão Renal Aguda/patologia , Adulto , Idoso , Biomarcadores/sangue , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Braz J Cardiovasc Surg ; 34(5): 565-571, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165612

RESUMO

OBJECTIVE: Acute kidney injury (AKI) is one of the most important complications after coronary artery bypass grafting (CABG) procedure. Serum albumin, which is an acute phase reactant, is suggested to be associated with AKI development subsequent to various surgical procedures. In this study, we research the relation between preoperative serum albumin levels and postoperative AKI development in diabetes mellitus (DM) patients undergoing isolated CABG. METHODS: We included a total of 634 diabetic patients undergoing CABG (60.5±9.1 years, 65.1% male) into this study, which was performed between September 2009 and January 2014 in a single center. The relation between preoperative serum albumin levels and postoperative AKI development was observed. AKI was evaluated and diagnosed using the Kidney Disease: Improving Global Outcomes (KDIGO) classification. RESULTS: AKI was diagnosed in 230 (36.3%) patients. Multiple logistic regression analysis was performed to determine the independent predictors of AKI development. Proteinuria (odds ratio [OR] and 95% confidence interval [CI], 1.066 [1.002-1.135]; P=0.043) and low preoperative serum albumin levels (OR and 95% CI, 0.453 [0.216-0.947]; P=0.035) were found to be independent predictors of AKI. According to the receiver operating characteristic curve analysis, albumin level <3mg/dL (area under the curve: 0.621 [0.572-0.669], P<0.001) had 83% sensitivity and 10% specificity on predicting the development of AKI. CONCLUSION: We observed that a preoperative low serum albumin level was associated with postoperative AKI development in patients with DM who underwent isolated CABG procedure. We emphasize that this adjustable albumin level should be considered before the operation since it is an easy and clinically implementable management for the prevention of AKI development.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Ponte de Artéria Coronária/efeitos adversos , Complicações do Diabetes/sangue , Hipoalbuminemia/sangue , Lesão Renal Aguda/diagnóstico , Idoso , Análise de Variância , Glicemia/análise , Índice de Massa Corporal , Creatinina/sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Período Pré-Operatório , Proteinúria , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Fatores de Tempo
19.
Clin Chim Acta ; 495: 552-555, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31175848

RESUMO

BACKGROUND: Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for predicting acute kidney injury (AKI). The purpose of this study was to evaluate the diagnostic performance of urinary NGAL in predicting AKI in sepsis patients in the emergency department. METHODS: A total of 140 patients were enrolled. We compared serum procalcitonin and urinary NGAL concentrations between patients with local infection, sepsis, and septic shock, and between patients who did and did not develop AKI with sepsis. Receiver-operating characteristic curve analysis was used to evaluate the ability to predict AKI in sepsis patients. RESULTS: Both serum procalcitonin and urinary NGAL concentrations were significantly higher in the sepsis and septic shock groups than in the local infection group (both p < 0.001). In sepsis patients, serum procalcitonin and urinary NGAL concentrations were higher in AKI patients than in those without AKI (p = 0.006, p < 0.001, respectively). The area under the curve for predicting of AKI was higher for a urinary NGAL of 0.820 (95% confidence interval (CI) 0.721-0.895) than for a serum procalcitonin concentration of 0.76 (95% CI 0.597-0.800). CONCLUSION: Urinary NGAL concentration may predict AKI in patients with sepsis in the emergency department.


Assuntos
Lesão Renal Aguda/complicações , Lesão Renal Aguda/urina , Serviço Hospitalar de Emergência , Lipocalina-2/urina , Sepse/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Curva ROC
20.
Med Sci Monit ; 25: 4362-4369, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185006

RESUMO

BACKGROUND Ischemia-reperfusion (I/R) leads to kidney injury. Renal I/R frequently occurs in kidney transplantations and acute kidney injuries. Recent studies reported that miR-30 stimulated immune responses and reductions in renal I/R related to anti-inflammation. Our study investigated the effects of miR-30c-5p on renal I/R and the relationship among miR-30c-5p, renal I/R, and macrophages. MATERIAL AND METHODS Sprague Dawley rats received intravenous tail injections of miR-30c-5p agomir. Then a renal I/R model were established by removing the left kidney and clamping the right renal artery. Serum creatinine (Cr) was analyzed using a serum Cr assay kit, and serum neutrophil gelatinase associated lipocalin (NGAL) was measured using a NGAL ELISA (enzyme-linked immunosorbent assay) kit. Rat kidney tissues were analyzed using hematoxylin and eosin staining. THP-1 cells treated with miR-30c-5p agomir and miR-30c-5p antagomir were measured with quantitative reverse transcription-polymerase chain reaction. Protein levels were analyzed by western blot. RESULTS MiR-30c-5p agomir reduced serum Cr, serum NGAL, and renal I/R injury. MiR-30c-5p agomir inhibited the expression of CD86 (M1 macrophage marker), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-alpha) and promoted the expression of CD206 (M2 macrophage marker), interleukin (IL)-4, and IL-10 in rat kidneys. MiR-30c-5p agomir reduced the expression of CD86 and iNOS, and increased the expression of CD206 and IL-10 in THP-1 cells. CONCLUSIONS We preliminarily demonstrated that miR-30c-5p agomir might decrease renal I/R through transformation of M1 macrophages to M2 macrophages and resulted in changes in inflammatory cytokines.


Assuntos
Lesão Renal Aguda/sangue , Macrófagos/metabolismo , MicroRNAs/sangue , Traumatismo por Reperfusão/sangue , Lesão Renal Aguda/genética , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Creatina/sangue , Humanos , Inflamação/sangue , Rim/irrigação sanguínea , Rim/patologia , Lipocalina-2/sangue , Macrófagos/patologia , Masculino , MicroRNAs/genética , Óxido Nítrico Sintase Tipo II/sangue , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Células THP-1 , Fator de Necrose Tumoral alfa/sangue
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