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Thèse de Doctorat
DOI
https://doi.org/10.11606/T.5.2024.tde-06052024-170046
Document
Auteur
Nom complet
Adriana de Queiroz Borges
Adresse Mail
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2024
Directeur
Jury
Farias, Alberto Queiroz (Président)
Andraus, Wellington
Gonçalves, Luciana Lofêgo
Malbouisson, Luiz Marcelo Sá
Titre en portugais
Marcadores bioquímicos e biológicos no diagnóstico diferencial entre lesão renal aguda pré-renal, síndrome hepatorrenal e necrose tubular aguda em pacientes com cirrose: estudo de acurácia diagnóstica
Mots-clés en portugais
Ascite
Cirrose
Fração de exceção de ureia
Fração de excreção de sódio
Infecções bacterianas
Lesão renal aguda
Necrose tubular aguda
NGAL urinária
Proteína de lipocalina associada à gelatinase dos neutrófilos humanos
Síndrome hepatorrenal
Resumé en portugais
Introdução: as três principais causas de LRA no paciente com cirrose são lesão pré-renal (ou induzida por hipovolemia), síndrome hepatorrenal e necrose tubular aguda (NTA). A diferenciação precoce entre as três condições possibilitaria estratégias terapêuticas individualizadas. Objetivo: avaliar a acurácia diagnóstica de marcadores bioquímicos e biológicos (fração de excreção de sódio, fração de excreção de ureia, relação NGAL/creatinina urinária) na distinção entre as três principais causas de LRA no paciente com cirrose. Os objetivos específicos foram: determinar o melhor ponto de corte dos diferentes marcadores; comparar o perfil dos diferentes marcadores de acordo com a causa da lesão renal aguda; combinar marcadores para melhorar a acurácia diagnóstica. Métodos: trata-se de um estudo prospectivo, multicêntrico nacional, delineado de acordo com a metodologia STARD Standards for Reporting of Diagnostic Accuracy Studies. Foram incluídos pacientes consecutivos com cirrose e ascite internados por descompensação da cirrose. Amostras de sangue e urina foram coletadas no momento da inclusão, ou em até 24 horas para determinação dos marcadores citados. O diagnóstico de LRA foi feito por adjudicação por 3 hepatologistas. Resultados: FENa com ponto de corte 0,4 apresentou acurácia 85%, especificidade 87%, sensibilidade 78%, VPP (valor preditivo positivo) 65%, VPN (valor preditivo negativo) 93%, LR- (razão de verossimilhança negativa) 2,4% e LR+ (razão de verossimilhança positiva) 62% para distinguir NTA das outras causas de LRA. NGAL/creatinina acima de 320 g/g apresentou acurácia 83%, especificidade 86%, sensibilidade 74%, VPP 63%, VPN 91%, LR- 3% e LR+ 54% para distinguir NTA de outras causas de LRA. Há importante sobreposição de valores da FENa e do NGAL na LRA. Entretanto, FENa< 0,2 é sugestivo de SHR e apresentou acurácia 65%, especificidade 62%, sensibilidade 69%, VPP 46%, VPN 81%, LR- 48% e LR+ 1,8 %. A FEUr teve acurácia 74% no ponto de Youden com especificidade de 87% VPP 38%, VPN 80%, LR- 84 %, LR+ 21% e acurácia 77% no ponto de rule in com especificadade de 96%, VPP 50%, VPN 78%, LR- 91 %, LR+ 3,4%. A associação de FENa e NGAL/creatinina aumentou a acurácia diagnóstica para diagnóstico de NTA e não-NTA (de 85% para 88%) a associação de FENa e FEUr aumentou de 85% para 89% (p<0,001)
Titre en anglais
Biochemical and biological markers in the differential diagnosis between prerenal acute kidney injury, hepatorenal syndrome and acute tubular necrosis in patients with cirrhosis: a diagnostic accuracy study
Mots-clés en anglais
Acute kidney injury
Ascites
Bacterial infections
Cirrhosis
Hepatorenal syndrome
Neutrophil gelatinase associated lipocalin
Sodium excretion fraction
Urea excretion fraction
Urinary NGAL
Resumé en anglais
Introduction: the three main causes of acute kidney injury (AKI) in patients with cirrhosis are pre-renal injury (or induced by hypovolemia), hepatorenal syndrome (HRS) and acute tubular necrosis (ATN). Early differentiation between the three conditions would enable individualized therapeutic strategies. Objective: to evaluate the diagnostic accuracy of biochemical and biological markers (sodium excretion fraction, urea excretion fraction, NGAL/urinary creatinine ratio) in distinguishing between the three main causes of AKI in patients with cirrhosis. The specific objectives were: to determine the best cutoff point for the different markers; compare the profile of different markers according to the cause of acute kidney injury; combine markers to improve diagnostic accuracy. Methods: this is a prospective, national multicenter study, designed according to the STARD methodology Standards for Reporting of Diagnostic Accuracy Studies. Consecutive patients with cirrhosis and ascites admitted due to decompensation of cirrhosis were included. Blood and urine samples were collected at the time of inclusion, or within 24 hours to determine the aforementioned markers. The diagnosis of AKI was made by adjudication by 3 hepatologists. Results: FENa with a cutoff point of 0.4 showed accuracy 85%, specificity 87%, sensitivity 78%, PPV (positive predictive value) 65%, NPV (negative predictive value) 93%, LR- (negative likelihood ratio) 24% and LR (positive likelihood ratio) 6,2% to distinguish NTA from other causes of AKI. NGAL/creatinine above 320 g/g showed accuracy 83%, specificity 86%, sensitivity 74%, PPV 63%, NPV 91%, LR- 30% and LR+ 5,4% to distinguish NTA from other causes of AKI. There is an important overlap in FENa and NGAL values in the LRA. However, FENa< 0.2 is suggestive of HRS and presented accuracy 65%, specificity 63%, sensitivity 69%, PPV 46%, NPV 81%, LR- 48% and LR+ 1,8%. The FEUr was 74% accurate, in Youden point (43,3), showed specificity 87%, sensitivity 26%, PPV (positive predictive value) 38%, NPV (negative predictive value) 80%, LR- (negative likelihood ratio) 8,4% and LR+ (positive likelihood ratio) 21% and with a cutoff point of 50,7 (rule in) showed accuracy 77%, specificity 96%, sensitivity 12%, PPV 50%, NPV 79%, LR- 9,1% and LR+ 34% to distinghis NTA from other causes of NTA. The association of FENa and NGAL/creatinine increased the diagnostic accuracy for diagnosing NTA and non-NTA (accuracy from 85% to 88%) p<0,001 and the association of FENa and FEUr incresead accuracy from 85% to 89% (p<0,001)
 
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Date de Publication
2024-05-28
 
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