Publication date: Available online 12 December 2017
Source:Translational Research
Author(s): Ayse L. Mindikoglu, Antone R. Opekun, Nagireddy Putluri, Sridevi Devaraj, David Sheikh-Hamad, John M. Vierling, John A. Goss, Abbas Rana, Gagan K. Sood, Prasun K. Jalal, Lesley A. Inker, Robert P. Mohney, Hocine Tighiouart, Robert H. Christenson, Thomas C. Dowling, Matthew R. Weir, Stephen L. Seliger, William R. Hutson, Charles D. Howell, Jean-Pierre Raufman, Laurence S. Magder, Cristian Coarfa
The application of non-targeted metabolomic profiling has recently become a powerful non-invasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultra-performance liquid chromatography/tandem mass spectrometry to identify preliminary metabolomic biomarker candidates. Among the 1028 metabolites identified, 34 were significantly increased in subjects with high liver and kidney disease severity compared to those with low liver and kidney disease severity. The highest average fold-change (2.39) was for 4-acetamidobutanoate. Metabolite-based enriched pathways were significantly associated with the identified metabolomic signature (P values ranged from 2.07E-06 to 0.02919). Ascorbate and aldarate metabolism, methylation, and glucuronidation were among the most significant protein-based enriched pathways associated with this metabolomic signature (P values ranged from 1.09E-18 to 7.61E-05). Erythronate had the highest association with measured GFR (R-square=0.571, P<0.0001). Erythronate (R=0.594, P<0.0001) and N6-carbamoylthreonyladenosine (R=0.591, P<0.0001) showed stronger associations with measured GFR compared to Cr (R=0.588, P<0.0001) even after controlling for age, gender and race. The 5 most significant metabolites that predicted mortality independent of kidney disease and demographics were S-adenosylhomocysteine (P=0.0003), glucuronate (P=0.0006), trans-aconitate (P=0.0018), 3-ureidopropionate (P=0.0021), and 3-(4-hydroxyphenyl)lactate (P=0.0047). A unique metabolomic signature associated with hepatorenal dysfunction in cirrhosis was identified for further investigations that provide potentially important mechanistic insights into cirrhosis-altered metabolism.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2nUiMya
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
-
Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
-
2016-11-22T07-55-59Z Source: International Journal of Medical Science and Public Health Banothu Srinivas, Madhu Mohan Reddy B. Backgrou...
-
2016-10-15T06-30-01Z Source: The Southeast Asian Journal of Case Report and Review Sangita Deepak Kamath, Neeraj Jain, Saurabh Pathak, Ba...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
-
Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου