Admission Urinary and Serum Metabolites Predict Renal Outcomes in Hospitalized Patients With Cirrhosis

• Type of Material: Article
• Authors: Ram Subramanian, Emory University; Jasmohan S Bajaj, Virginia Commonwealth University; Guadalupe Garcia-Tsao, Yale University; Rajender K Reddy, University of Pennsylvania; Jacqueline G O'Leary, Dallas Veterans Affairs Medical Center; Hugo E Vargas, Mayo Clinic Arizona; Jennifer C Lai, University of California San Francisco; Patrick S Kamath, Mayo Clinic Rochester; Puneeta Tandon, University of Alberta; Paul Thuluvath, Mercy Medical Center; Andrew Fagan, Virginia Commonwealth University; Tejasav Sehrawat, Mayo Clinic Rochester; Randolph De La Rosa Rodriguez, Yale University; Leroy R Thacker, Virginia Commonwealth University; Florence Wong, University of Toronto
• Language: English
• Date: 2021-07-08
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 by the American Association for the Study of Liver Diseases.
• Final Published Version (URL): http://dx.doi.org/10.1002/hep.31907
• Title of Journal or Parent Work: HEPATOLOGY
• Volume: 74
• Issue: 5
• Start Page: 2699
• End Page: 2713
• Grant/Funding Information: Supported by VA Merit Review (I0CX00176) and National Center for Advancing Translational Sciences/National Institutes of Health (R21TR003095 and R21TR002024) and investigator-initiated grants from Grifols and Mallinckrodt Pharmaceuticals; Additional support was received from the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK026743)
• Keywords: ASSOCIATION; MANAGEMENT; ACUTE KIDNEY INJURY; KYNURENINE PATHWAY; Life Sciences & Biomedicine; Gastroenterology & Hepatology; Science & Technology; DIAGNOSIS; REVISED CONSENSUS RECOMMENDATIONS; MORTALITY; INTERNATIONAL CLUB; DISEASE

Abstract

Background and Aims: Acute kidney injury (AKI) has a poor prognosis in cirrhosis. Given the variability of creatinine, the prediction of AKI and dialysis by other markers is needed. The aim of this study is to determine the role of serum and urine metabolomics in the prediction of AKI and dialysis in an inpatient cirrhosis cohort. Approach and Results: Inpatients with cirrhosis from 11 North American Consortium of End-stage Liver Disease centers who provided admission serum/urine when they were AKI and dialysis-free were included. Analysis of covariance adjusted for demographics, infection, and cirrhosis severity was performed to identify metabolites that differed among patients (1) who developed AKI or not; (2) required dialysis or not; and/pr (3) within AKI subgroups who needed dialysis or not. We performed random forest and AUC analyses to identify specific metabolite(s) associated with outcomes. Logistic regression with clinical variables with/without metabolites was performed. A total of 602 patients gave serum (218 developed AKI, 80 needed dialysis) and 435 gave urine (164 developed AKI, 61 needed dialysis). For AKI prediction, clinical factor–adjusted AUC was 0.91 for serum and 0.88 for urine. Major metabolites such as uremic toxins (2,3-dihydroxy-5-methylthio-4-pentenoic acid [DMTPA], N2N2dimethylguanosine, uridine/pseudouridine) and tryptophan/tyrosine metabolites (kynunerate, 8-methoxykyunerate, quinolinate) were higher in patients who developed AKI. For dialysis prediction, clinical factor–adjusted AUC was 0.93 for serum and 0.91 for urine. Similar metabolites as AKI were altered here. For dialysis prediction in those with AKI, the AUC was 0.81 and 0.79 for serum/urine. Lower branched-chain amino-acid (BCAA) metabolites but higher cysteine, tryptophan, glutamate, and DMTPA were seen in patients with AKI needing dialysis. Serum/urine metabolites were additive to clinical variables for all outcomes. Conclusions: Specific admission urinary and serum metabolites were significantly additive to clinical variables to predict AKI development and dialysis initiation in inpatients with cirrhosis. These observations can potentially facilitate earlier initiation of renoprotective measures.