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1.
Nat Commun ; 11(1): 5668, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168827

RESUMO

Artificial intelligence (AI) has demonstrated promise in predicting acute kidney injury (AKI), however, clinical adoption of these models requires interpretability and transportability. Non-interoperable data across hospitals is a major barrier to model transportability. Here, we leverage the US PCORnet platform to develop an AKI prediction model and assess its transportability across six independent health systems. Our work demonstrates that cross-site performance deterioration is likely and reveals heterogeneity of risk factors across populations to be the cause. Therefore, no matter how accurate an AI model is trained at the source hospital, whether it can be adopted at target hospitals is an unanswered question. To fill the research gap, we derive a method to predict the transportability of AI models which can accelerate the adaptation process of external AI models in hospitals.


Assuntos
Lesão Renal Aguda/etiologia , Inteligência Artificial , Aprendizado de Máquina , Lesão Renal Aguda/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco , Fatores de Risco , Adulto Jovem
2.
JAMA ; 324(16): 1629-1639, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33095849

RESUMO

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02669589.


Assuntos
Lesão Renal Aguda/terapia , Anticoagulantes/administração & dosagem , Ácido Cítrico/administração & dosagem , Terapia de Substituição Renal Contínua/instrumentação , Heparina/administração & dosagem , Lesão Renal Aguda/sangue , Lesão Renal Aguda/mortalidade , Idoso , Anticoagulantes/efeitos adversos , Cálcio/sangue , Ácido Cítrico/efeitos adversos , Terapia de Substituição Renal Contínua/mortalidade , Estado Terminal , Término Precoce de Ensaios Clínicos , Feminino , Filtração/instrumentação , Alemanha , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Heparina/efeitos adversos , Humanos , Infecções/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Tempo de Tromboplastina Parcial , Modelos de Riscos Proporcionais , Fatores de Tempo
3.
PLoS One ; 15(10): e0239770, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052974

RESUMO

Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.


Assuntos
Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/fisiopatologia , Microcirculação/fisiologia , Sepse/fisiopatologia , Lesão Renal Aguda/sangue , Estudos de Coortes , Creatinina/sangue , Feminino , Hidratação/métodos , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perfusão/métodos , Prognóstico , Sepse/sangue , Sepse/mortalidade , Equilíbrio Hidroeletrolítico/fisiologia
5.
J Am Soc Nephrol ; 31(11): 2725-2735, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32963090

RESUMO

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias
6.
Toxicol Lett ; 334: 21-26, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910981

RESUMO

MicroRNAs are key regulators of the normal kidney function and development, and altered in acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum microRNAs, with and without kidney injury, after human oxalic acid poisoning. We profiled urinary microRNAs in patients who ingested oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary microRNAs and lower expression of serum microRNAs. Most urine microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion. Poisoning irrespective of AKI led to significantly lower expression of many microRNAs in serum but relatively few changes in urinary miRNA expression. In conclusion, urinary microRNA signature provides a stronger measure of AKI in oxalic acid poisoning compared to serum microRNA. Kidney injury has the greatest impact on urinary microRNA, while poisoning itself was better reflected in serum miRNA. Plasma and urinary microRNAs signatures provide complementary information in toxic kidney injury.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , MicroRNAs , Ácido Oxálico/envenenamento , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/genética , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Coortes , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , MicroRNAs/sangue , MicroRNAs/urina
7.
PLoS One ; 15(9): e0238867, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915900

RESUMO

BACKGROUND: Hypophosphatemia and hypokalemia occur frequently during continuous renal replacement therapy (CRRT). We evaluated serum phosphate and potassium levels in patients administered three different types of dialysis solution. METHODS: The study population consisted of 324 intensive care unit patients who underwent CRRT between January 2015 and December 2018. Patients were divided into three groups: group 1 (n = 105) received Hemosol B0 (no potassium or phosphate); group 2 (n = 78) received Hemosol B0 and potassium-containing solution (MultiBic); and group 3 (n = 141) received phosphate- and potassium-containing solution (Phoxilium), Hemosol B2, Prismasol 2, and Prismasol 4. A different protocol was followed in each group. RESULTS: The incidence rate of hypophosphatemia was 55% lower in group 3 compared to group 1 (incidence rate ratio (IRR) 0.45, 95% confidence interval (CI): 0.33 to 0.61) and 61% lower compared to group 2 (IRR 0.39, 95% CI: 0.29 to 0.53). Group 3 also had a 50% lower incidence rate of hypokalemia compared to group 1 (IRR 0.50, 95% CI: 0.29 to 0.88). The negative slope in phosphate level in group 3 was greater than that in group 1 (ß = 0.19, 95% CI: 0.02 to 0.37, p = 0.032), while the negative slope in the potassium level was greater in group 2 than in group 1(ß = 0.10, 95% CI: 0.03 to 0.17, p = 0.008). Additional intravenous calcium was not used in any case, and most cases of acid-base disturbances were well controlled. CONCLUSIONS: The use of phosphate- and potassium-containing with a proper CRRT protocol prevented decreases in serum phosphate and potassium levels, thus also preventing hypophosphatemia and hypokalemia, and additional replacement during CRRT.


Assuntos
Lesão Renal Aguda/terapia , Terapia de Substituição Renal Contínua/métodos , Soluções para Diálise/química , Eletrólitos/química , Fosfatos/administração & dosagem , Potássio/administração & dosagem , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Idoso , Feminino , Humanos , Hipopotassemia/prevenção & controle , Hipofosfatemia/prevenção & controle , Unidades de Terapia Intensiva , Masculino , Fosfatos/sangue , Potássio/sangue , Estudos Retrospectivos
8.
Stroke ; 51(10): 3030-3038, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32838673

RESUMO

BACKGROUND AND PURPOSE: We determined the rates and predictors of acute kidney injury (AKI) and renal adverse events (AEs), and effects of AKI and renal AEs on death or disability in patients with intracerebral hemorrhage. METHODS: We analyzed data from a multicenter trial which randomized 1000 intracerebral hemorrhage patients with initial systolic blood pressure ≥180 mm Hg to intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure reduction within 4.5 hours of symptom onset. AKI was identified by serial assessment of daily serum creatinine for 3 days post randomization. RESULTS: AKI and renal AEs were observed in 149 patients (14.9%) and 65 patients (6.5%) among 1000 patients, respectively. In multivariate analysis, the higher baseline serum creatinine (≥110 µmol/L) was associated with AKI (odds ratio 2.4 [95% CI, 1.2-4.5]) and renal AEs (odds ratio 3.1 [95% CI, 1.2-8.1]). Higher area under the curve for intravenous nicardipine dose was associated with AKI (odds ratio 1.003 [95% CI, 1.001-1.005]) and renal AEs (odds ratio 1.003 [95% CI, 1.001-1.006]). There was a higher risk to death (relative risk 2.6 [95% CI, 1.6-4.2]) and death or disability (relative risk 1.5 [95% CI, 1.3-1.8]) at 90 days in patients with AKI but not in those with renal AEs. CONCLUSIONS: Intracerebral hemorrhage patients with higher baseline serum creatinine and those receiving higher doses of nicardipine were at higher risk for AKI and renal AEs. Occurrence of AKI was associated higher rates of death or disability at 3 months. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01176565.


Assuntos
Lesão Renal Aguda/etiologia , Pressão Sanguínea/fisiologia , Hemorragia Cerebral/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/fisiopatologia , Fatores Etários , Idoso , Hemorragia Cerebral/sangue , Hemorragia Cerebral/fisiopatologia , Creatinina/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
9.
Transplantation ; 104(8): 1553-1559, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732831

RESUMO

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.


Assuntos
Lesão Renal Aguda/diagnóstico , Função Retardada do Enxerto/epidemiologia , Seleção do Doador/métodos , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Aloenxertos/provisão & distribução , Biomarcadores/análise , Biópsia , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Seleção do Doador/normas , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Humanos , Rim/patologia , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/normas , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
10.
Nat Commun ; 11(1): 3852, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737308

RESUMO

Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Early clinical prediction is typically based on manually calculated screening metrics that simply weigh these parameters, such as early warning scores (EWS). The predictive performance of EWSs yields a tradeoff between sensitivity and specificity that can lead to negative outcomes for the patient. Previous work on electronic health records (EHR) trained artificial intelligence (AI) systems offers promising results with high levels of predictive performance in relation to the early, real-time prediction of acute critical illness. However, without insight into the complex decisions by such system, clinical translation is hindered. Here, we present an explainable AI early warning score (xAI-EWS) system for early detection of acute critical illness. xAI-EWS potentiates clinical translation by accompanying a prediction with information on the EHR data explaining it.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Pulmonar Aguda/diagnóstico , Inteligência Artificial , Registros Eletrônicos de Saúde/estatística & dados numéricos , Sepse/diagnóstico , Doença Aguda , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/patologia , Área Sob a Curva , Pressão Sanguínea , Estado Terminal , Diagnóstico Precoce , Frequência Cardíaca , Humanos , Prognóstico , Curva ROC , Sepse/sangue , Sepse/patologia
11.
Ann Hematol ; 99(10): 2303-2313, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32856141

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease characterized by a deregulated complement system, chronic Coombs-negative, intravascular hemolysis, and a variable clinical course with substantial risk to develop thromboembolic events. We analyzed diagnostic and prognostic parameters as well as clinical endpoints in 59 adult patients suffering from PNH in 5 hematology centers in Austria (observation period: 1978-2015). Median follow-up time was 5.6 years. The median clone size at diagnosis amounted to 55% and was higher in patients with classical PNH (81%) compared to patients with PNH associated with aplastic anemia (AA) or myelodysplastic syndromes (MDS) (50%). The clone size also correlated with lactate dehydrogenase (LDH) levels. In one patient, anemia improved spontaneously and disappeared with complete normalization of LDH after 16 years. Seventeen patients received therapy with eculizumab. The rate of thromboembolic events was higher in the pre-eculizumab era compared with eculizumab-treated patients but did not correlate with the presence of age-related clonal hematopoiesis or any other clinical or laboratory parameters. Peripheral blood colony-forming progenitor cell counts were lower in PNH patients compared with healthy controls. Only two patients with classical PNH developed MDS. Overall, 7/59 patients died after 0.5-32 years. Causes of death were acute pulmonary hypertension, Budd-Chiari syndrome, and septicemia. Overall survival (OS) was mainly influenced by age and was similar to OS measured in an age-matched healthy Austrian control cohort. Together, compared with previous times, the clinical course and OS in PNH are favorable, which may be due to better diagnosis, early recognition, and eculizumab therapy.


Assuntos
Hemoglobinúria Paroxística/epidemiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Adulto , Anemia Aplástica/epidemiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Áustria/epidemiologia , Medula Óssea/patologia , Causas de Morte , Células Clonais/patologia , Ensaio de Unidades Formadoras de Colônias , Terapia Combinada , Inativadores do Complemento/uso terapêutico , Creatinina/sangue , Progressão da Doença , Feminino , Seguimentos , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/epidemiologia , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Prognóstico , Tromboembolia/etiologia
12.
BMJ Case Rep ; 13(8)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32784239

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy.


Assuntos
Lesão Renal Aguda/complicações , Betacoronavirus , Infecções por Coronavirus/complicações , Fígado Gorduroso/complicações , Síndrome HELLP/diagnóstico , Pneumonia Viral/complicações , Pré-Eclâmpsia/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Adulto , Infecções por Coronavirus/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Feminino , Síndrome HELLP/sangue , Humanos , Testes de Função Renal , Pandemias , Pneumonia Viral/sangue , Pré-Eclâmpsia/sangue , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/sangue
14.
Surgery ; 168(4): 662-670, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32600883

RESUMO

BACKGROUND: Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to investigate combat-related post-traumatic acute kidney injury in recent military conflicts, used machine learning algorithms to identify clinical and biomarker variables associated with the development of post-traumatic acute kidney injury, and evaluated the effects of post-traumatic acute kidney injury on wound healing and nosocomial infection. METHODS: We conducted a retrospective clinical cohort review of 73 critically injured US military service members who sustained major combat-related extremity wounds and had collected injury characteristics, assayed serum and tissue biopsy samples for the expression of protein and messenger ribonucleic acid biomarkers. Bivariate analyses and random forest recursive feature elimination classification algorithms were used to identify associated injury characteristics and biomarker variables. RESULTS: The incidence of post-traumatic acute kidney injury was 20.5%. Of that, 86% recovered baseline renal function and only 2 (15%) of the acute kidney injury group required renal replacement therapy. Random forest recursive feature elimination algorithms were able to estimate post-traumatic acute kidney injury with the area under the curve of 0.93, sensitivity of 0.91, and specificity of 0.91. Post-traumatic acute kidney injury was associated with injury severity score, serum epidermal growth factor, and tissue activin A type receptor 1, matrix metallopeptidase 10, and X-C motif chemokine ligand 1 expression. Patients with post-traumatic acute kidney injury exhibited poor wound healing and increased incidence of nosocomial infections. CONCLUSION: The occurrence of acute kidney injury in combat casualties may be estimated using injury characteristics and serum and tissue biomarkers. External validations of these models are necessary to generalize for all trauma patients.


Assuntos
Lesão Renal Aguda/diagnóstico , Citocinas/sangue , Inflamação/sangue , Lesões Relacionadas à Guerra/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Adulto , Campanha Afegã de 2001- , Algoritmos , Biomarcadores/sangue , Infecção Hospitalar/complicações , Diagnóstico Precoce , Feminino , Humanos , Incidência , Escala de Gravidade do Ferimento , Guerra do Iraque 2003-2011 , Aprendizado de Máquina , Masculino , Militares , Estudos Retrospectivos , Fatores de Risco , Cicatrização , Adulto Jovem
15.
Bratisl Lek Listy ; 121(8): 565-570, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726119

RESUMO

OBJECTIVES: The effectiveness of the myo-inositol oxygenase (MIOX) enzyme was investigated in the diagnosis of acute kidney injury (AKI). METHODS: In total, 40 rats were divided into 5 groups (n = 8, for each group) while left kidney ischemia-reperfusion was implemented in groups 2, 3, 4 and 5. Group 1 was the control group. Group 2 underwent 1­hour ischemia and 2­hour reperfusion. Group 3 underwent 1­hour ischemia and 4­hour reperfusion. Group 4 underwent 2­hour ischemia and 2­hour reperfusion. Group 5 underwent 2­hour ischemia and 4­hour reperfusion. RESULTS: Serum creatinine and blood urea nitrogen levels in all ischemia-reperfusion groups were higher than in the control group (p<0.001). Serum MIOX level was higher in groups 2, 3 and 4 than in group 1 (p=0.002). Tissue MIOX level was lower in groups 2, 4, and 5 than in group 1 (p=0.039). Serum and tissue neutrophil gelatinase-associated lipocalin levels were not significantly different between the groups. The injury level in histopathologic examination was as follows: group 1

Assuntos
Lesão Renal Aguda , Inositol Oxigenase , Traumatismo por Reperfusão , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/enzimologia , Animais , Biomarcadores/sangue , Creatinina , Diagnóstico Precoce , Inositol Oxigenase/sangue , Rim , Ratos , Traumatismo por Reperfusão/diagnóstico
16.
Nat Commun ; 11(1): 2788, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493916

RESUMO

Oxidative stress is associated with many acute and chronic inflammatory diseases, yet limited treatment is currently available clinically. The development of enzyme-mimicking nanomaterials (nanozymes) with good reactive oxygen species (ROS) scavenging ability and biocompatibility is a promising way for the treatment of ROS-related inflammation. Herein we report a simple and efficient one-step development of ultrasmall Cu5.4O nanoparticles (Cu5.4O USNPs) with multiple enzyme-mimicking and broad-spectrum ROS scavenging ability for the treatment of ROS-related diseases. Cu5.4O USNPs simultaneously possessing catalase-, superoxide dismutase-, and glutathione peroxidase-mimicking enzyme properties exhibit cytoprotective effects against ROS-mediated damage at extremely low dosage and significantly improve treatment outcomes in acute kidney injury, acute liver injury and wound healing. Meanwhile, the ultrasmall size of Cu5.4O USNPs enables rapid renal clearance of the nanomaterial, guaranteeing the biocompatibility. The protective effect and good biocompatibility of Cu5.4O USNPs will facilitate clinical treatment of ROS-related diseases and enable the development of next-generation nanozymes.


Assuntos
Cobre/química , Depuradores de Radicais Livres/química , Inflamação/patologia , Nanopartículas/química , Tamanho da Partícula , Espécies Reativas de Oxigênio/química , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Lesão Renal Aguda/terapia , Alanina Transaminase/sangue , Animais , Antioxidantes/química , Aspartato Aminotransferases/sangue , Bovinos , Cobre/farmacocinética , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Análise de Componente Principal , Ratos Sprague-Dawley , Distribuição Tecidual , Cicatrização
18.
Crit Care Resusc ; 22(2): 142-151, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389106

RESUMO

BACKGROUND: Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. OBJECTIVE: To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. METHODS: We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. RESULTS: We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 µmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. CONCLUSION: In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.


Assuntos
Lesão Renal Aguda , Biomarcadores/urina , Pontos de Checagem do Ciclo Celular/fisiologia , Urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Creatinina/sangue , Estado Terminal , Taxa de Filtração Glomerular , Humanos , Unidades de Terapia Intensiva , Testes de Função Renal , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Micção
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 313-318, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32385995

RESUMO

OBJECTIVE: To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China. METHODS: A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKISCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL×min-1×1.73 m-2, and AoCKD was defined as meeting the KDIGO-AKISCr standard and baseline eGFR was 15-59 mL×min-1×1.73 m-2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. RESULTS: Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients (n = 322), AoCKD patients (n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation II (APACHE II) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL×min-1×1.73 m-2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (µmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ 2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio (HR) = 4.458, 95% confidence interval (95%CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU (HR = 5.181, 95%CI was 2.033-13.199, P = 0.001), and AoCKD (HR = 5.377, 95%CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. CONCLUSIONS: Further detailed classification (PAKI, AoCKD) based on KDIGO-AKISCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.


Assuntos
Lesão Renal Aguda/sangue , Creatinina/sangue , Adulto , China , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , Terapia de Substituição Renal , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 319-323, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32385996

RESUMO

OBJECTIVE: To observe the relationship between pulmonary artery systolic pressure (PASP) and acute renal injury (AKI) and prognosis after cardiopulmonary bypass (CPB) heart surgery. METHODS: The clinical data of 9 860 patients who underwent CPB heart surgery in Beijing Anzhen Hospital from January 1st, 2015 to December 31st, 2016 were analyzed retrospectively. The patients were divided into two groups according to whether AKI occurred after operation. The clinical data were obtained from hospital information system (HIS) and DoCare including general information, types of operation, preoperative complication, ejection fraction, serum creatinine (SCr), PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, blood products and drug usage, postoperative mechanical ventilation duration, length of intensive care unit (ICU) and hospital stay, and perioperative central venous pressure (CVP). Multivariate Logistic regression analysis was used to screen the risk factors of AKI after operation. According to the preoperative PASP level, the patients were divided into ≥ 60 mmHg (1 mmHg = 0.133 kPa) group and < 60 mmHg group, and the incidence of AKI and prognosis after operation were compared between the two groups. All patients were followed up by telephone after discharge, and they were divided into survival group and death group according to the follow-up results, and the clinical data were compared between the two groups. Multivariate Cox regression analysis was used to screen the risk factors of long-term prognosis. Kaplan-Meier survival curve was used to analyze the long-term prognosis of two groups with different preoperative PASP levels. RESULTS: 6 285 patients were enrolled in the final analysis. (1) Among the 6 285 patients, 2 592 patients (41.2%) suffered from AKI after operation, of whom 1 697 (65.5%) were stage 1 according to Kidney Disease: Improving Global Outcomes (KDIGO), which was the main type of AKI. Univariate analysis showed that age, preoperative ejection fraction, SCr, PASP, coronary heart disease, hypertension, diabetes, intraoperative CPB duration, aortic occlusion duration, fluid balance, red blood cell input and norepinephrine, dopamine, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be the risk factors of AKI after operation. Multivariate Logistic regression analysis showed that preoperative PASP was one of independent risk factors for AKI in patients undergoing CPB heart surgery [odds ratio (OR) = 4.753, 95% confidence interval (95%CI) was 1.328-8.417, P = 0.004]. The incidence of AKI after operation in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [73.8% (712/965) vs. 35.3% (1 880/5 320), P < 0.01]. (2) After a follow-up of (11±3) months, 237 patients (3.8%) died in 6 285 patients. The mortality of patients in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [9.5% (92/965) vs. 2.7% (145/5 320), P < 0.01]. Kaplan-Meier survival curve analysis showed that there was a significant difference between the two groups in cumulative survival rate (Log-Rank test: χ2 = 144.400, P < 0.001). Univariate analysis showed that male, age, preoperative hypertension, ejection fraction, PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be risk factors for long-term death of patients undergoing CPB heart surgery. Multivariate Cox regression analysis showed that for every 1 mmHg increase in preoperative PASP, the long-term mortality increased by 1.126 times [hazard ratio (HR) = 1.126, 95%CI was 1.003-1.604, P = 0.021]. CONCLUSIONS: The increase of PASP is related to AKI after CPB heart surgery, which is an independent risk factor for long-term mortality.


Assuntos
Lesão Renal Aguda/diagnóstico , Pressão Sanguínea , Ponte Cardiopulmonar , Lesão Renal Aguda/sangue , Humanos , Complicações Pós-Operatórias , Prognóstico , Artéria Pulmonar , Estudos Retrospectivos , Fatores de Risco
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