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1. WO2020064995 - USE OF BIOMARKERS REPRESENTING CARDIAC, VASCULAR AND INFLAMMATORY PATHWAYS FOR THE PREDICTION OF ACUTE KIDNEY INJURY IN PATIENTS WITH TYPE 2 DIABETES

Publication Number WO/2020/064995
Publication Date 02.04.2020
International Application No. PCT/EP2019/076155
International Filing Date 27.09.2019
IPC
G01N 33/68 2006.01
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48Biological material, e.g. blood, urine; Haemocytometers
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68involving proteins, peptides or amino acids
CPC
G01N 2800/042
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
04Endocrine or metabolic disorders
042Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
G01N 2800/347
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
34Genitourinary disorders
347Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy
G01N 2800/50
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2800Detection or diagnosis of diseases
50Determining the risk of developing a disease
G01N 33/6893
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
48Biological material, e.g. blood, urine
50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68involving proteins, peptides or amino acids
6893related to diseases not provided for elsewhere
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • UNIVERSITÉ DE POITIERS [FR]/[FR]
  • CENTRE HOSPITALIER UNIVERSITAIRE DE POITIERS [FR]/[FR]
Inventors
  • SAULNIER, Pierre Jean
Agents
  • INSERM TRANSFERT
Priority Data
18306273.628.09.2018EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) USE OF BIOMARKERS REPRESENTING CARDIAC, VASCULAR AND INFLAMMATORY PATHWAYS FOR THE PREDICTION OF ACUTE KIDNEY INJURY IN PATIENTS WITH TYPE 2 DIABETES
(FR) UTILISATION DE BIOMARQUEURS REPRÉSENTANT DES VOIES CARDIAQUES, VASCULAIRES ET INFLAMMATOIRES PERMETTANT LA PRÉDICTION D'UNE LÉSION RÉNALE AIGUË CHEZ DES PATIENTS ATTEINTS DE DIABÈTE DE TYPE 2
Abstract
(EN)
Acute kidney injury (AKI) is a related to chronic kidney disease and death in patients from the general population, with or without type 2 diabetes. Nevertheless AKI biomarkers are rarely validated in diabetes population. The inventors aimed to explore the individual and combined prognostic value of 7 circulating candidate markers for AKI. This include markers of cardiac and endothelial dysfunction (mid-regional-pro-adrenomedullin [MRproADM], angiopoietinlike-2 [ANGPTL2], N-terminal prohormone brain natriuretic peptide [NTproBNP]) oxidative stress (fluorescent advanced glycation endproducts [AGE], carbonyls), cardio-renal pathways (copeptin [CTproAVP]), and inflammation (soluble TNF receptor 1 [TNFR1]). They prospectively followed-up 1345 (565 women/780 men) type 2 diabetes participants of a French single-centre hospital-based cohort (SURDIAGENE). In univariate analysis, each biomarker was significantly associated with AKI, and 6 remained associated after multivariable adjustment. The addition of a multimarker score summing standardized and weighted values of these 6 markers to the model including usual risk factors significantly improved C-statistics (0.724 to 0.759, P<0.0001), and 5-year risk-predictive performance (relative integrated discrimination improvement index=0.435, P<0.0001). Thus the panel of 6 biomarkers representing cardiac, vascular and inflammatory pathways improves the prediction of AKI over usual risk factors in patients with type 2 diabetes.
(FR)
L'invention porte sur la prédiction d'une lésion rénale aiguë (AKI) qui est une maladie liée à une maladie rénale chronique et à la mort chez des patients issus de la population générale, atteints ou non de diabète de type 2. Néanmoins, les biomarqueurs d'AKI sont rarement validés dans la population atteinte de diabète. Les inventeurs ont cherché à explorer une valeur pronostique individuelle et combinée de 7 marqueurs candidats circulants d'une AKI. Les marqueurs comprennent des marqueurs de dysfonctionnement cardiaque et endothélial (pro-adrénomédulline [MRproADM], angiopoïétine-2 [ANGPTL2], peptide natriurétique du cerveau de prohormone N-terminale [NTproBNP]), stress oxydatif (produits terminaux de glycation avancée fluorescents [AGE], carbonyles), voies cardio-rénales (copeptine [CTproAVP]), et inflammation (récepteur TNF soluble 1 [TNFR1]). Ils ont suivi de manière prospective 1345 participants (565 femmes/780 hommes) atteint de diabète de type 2 issus d'une cohorte d'un hôpital français à centre unique (SURDIAGENE). Dans une analyse univariée, chaque biomarqueur a été significativement associé à une AKI, et 6 sont restés associés après un réglage multivariable. L'ajout d'un score multimarqueur qui additionne des valeurs normalisées et pondérées desdits 6 marqueurs au modèle comprend des statistiques C significativement améliorées de facteurs de risque habituels (0,724 à 0,759, P<0,0001), et de performances prédictives de risque à 5 ans (indice d'amélioration de discrimination intégrée relative =0,435, P<0,0001). Ainsi, le panel de 6 biomarqueurs représentant des voies cardiaques, vasculaires et inflammatoires améliore la prédiction d'AKI sur des facteurs de risque usuels chez des patients atteints de diabète de type 2.
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