Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis

Background. Acute kidney injury (AKI) is a frequent complication of decompensated cirrhosis with increased mortality. Traditional biomarkers such as serum creatinine are not sensitive for detecting injury without functional change. We hypothesize that urinary exosomes potentially carry markers that...

Full description

Bibliographic Details
Main Authors: Linda Awdishu, Shirley Tsunoda, Michelle Pearlman, Chanthel Kokoy-Mondragon, Majid Ghassemian, Robert K. Naviaux, Heather M. Patton, Ravindra L. Mehta, Bhavya Vijay, Satish P. RamachandraRao
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:Critical Care Research and Practice
Online Access:http://dx.doi.org/10.1155/2019/5912804
id doaj-ea7e7ca4d3fa40eba581855f5a3de637
record_format Article
spelling doaj-ea7e7ca4d3fa40eba581855f5a3de6372020-11-24T22:11:41ZengHindawi LimitedCritical Care Research and Practice2090-13052090-13132019-01-01201910.1155/2019/59128045912804Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with CirrhosisLinda Awdishu0Shirley Tsunoda1Michelle Pearlman2Chanthel Kokoy-Mondragon3Majid Ghassemian4Robert K. Naviaux5Heather M. Patton6Ravindra L. Mehta7Bhavya Vijay8Satish P. RamachandraRao9UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, USAUC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, USAUC San Diego, Department of Medicine, Division of Gastroenterology, San Diego, USABiomarkers Laboratory, O’Brien Center for Acute Kidney Injury Research, Nephrology-Hypertension, UC San Diego, Department of Medicine, San Diego, USAUC San Diego, Department of Chemistry & Biochemistry, Biomolecular & Proteomics Spectrometry Facility, San Diego, USAUC San Diego, Departments of Medicine, Pediatrics and Pathology, San Diego, USAUC San Diego, Department of Medicine, Division of Gastroenterology, San Diego, USABiomarkers Laboratory, O’Brien Center for Acute Kidney Injury Research, Nephrology-Hypertension, UC San Diego, Department of Medicine, San Diego, USAI-AIM Biomarkers Laboratory, The University of Trans-Disciplinary Health Sciences and Technology (TDU), Bangalore, IndiaBiomarkers Laboratory, O’Brien Center for Acute Kidney Injury Research, Nephrology-Hypertension, UC San Diego, Department of Medicine, San Diego, USABackground. Acute kidney injury (AKI) is a frequent complication of decompensated cirrhosis with increased mortality. Traditional biomarkers such as serum creatinine are not sensitive for detecting injury without functional change. We hypothesize that urinary exosomes potentially carry markers that differentiate the type of kidney injury in cirrhotic patients. Methods. This is a prospective, single-center, and observational study of adult patients with cirrhosis. The patient groups included healthy normal controls, compensated cirrhosis with normal kidney function, decompensated cirrhosis with normal kidney function, and decompensated cirrhosis with AKI. Data were extracted from the electronic health record including etiology of liver disease, MELD score, history of decompensation, Child-Turcotte-Pugh score, history of AKI, and medication exposures. Urine samples were collected at the time of consent. Urine exosome protein content was analyzed, and proteomic data were validated by immunoblotting. Statistical analysis included partial least squares-discriminant analysis coupled with variable importance in projection identification. Results. Eighteen cirrhotic subjects were enrolled, and six healthy control subjects were extracted from our biorepository. Urine exosomes were isolated, and 1572 proteins were identified. Maltase-glucoamylase was the top discriminating protein confirmed by western blotting. Conclusions. Patients with cirrhosis and AKI have upregulation of renal brush border disaccharidase, MGAM, in urinary exosomes which may differentiate the type of kidney injury in cirrhosis; however, the clinical significance of this requires further validation.http://dx.doi.org/10.1155/2019/5912804
collection DOAJ
language English
format Article
sources DOAJ
author Linda Awdishu
Shirley Tsunoda
Michelle Pearlman
Chanthel Kokoy-Mondragon
Majid Ghassemian
Robert K. Naviaux
Heather M. Patton
Ravindra L. Mehta
Bhavya Vijay
Satish P. RamachandraRao
spellingShingle Linda Awdishu
Shirley Tsunoda
Michelle Pearlman
Chanthel Kokoy-Mondragon
Majid Ghassemian
Robert K. Naviaux
Heather M. Patton
Ravindra L. Mehta
Bhavya Vijay
Satish P. RamachandraRao
Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
Critical Care Research and Practice
author_facet Linda Awdishu
Shirley Tsunoda
Michelle Pearlman
Chanthel Kokoy-Mondragon
Majid Ghassemian
Robert K. Naviaux
Heather M. Patton
Ravindra L. Mehta
Bhavya Vijay
Satish P. RamachandraRao
author_sort Linda Awdishu
title Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
title_short Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
title_full Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
title_fullStr Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
title_full_unstemmed Identification of Maltase Glucoamylase as a Biomarker of Acute Kidney Injury in Patients with Cirrhosis
title_sort identification of maltase glucoamylase as a biomarker of acute kidney injury in patients with cirrhosis
publisher Hindawi Limited
series Critical Care Research and Practice
issn 2090-1305
2090-1313
publishDate 2019-01-01
description Background. Acute kidney injury (AKI) is a frequent complication of decompensated cirrhosis with increased mortality. Traditional biomarkers such as serum creatinine are not sensitive for detecting injury without functional change. We hypothesize that urinary exosomes potentially carry markers that differentiate the type of kidney injury in cirrhotic patients. Methods. This is a prospective, single-center, and observational study of adult patients with cirrhosis. The patient groups included healthy normal controls, compensated cirrhosis with normal kidney function, decompensated cirrhosis with normal kidney function, and decompensated cirrhosis with AKI. Data were extracted from the electronic health record including etiology of liver disease, MELD score, history of decompensation, Child-Turcotte-Pugh score, history of AKI, and medication exposures. Urine samples were collected at the time of consent. Urine exosome protein content was analyzed, and proteomic data were validated by immunoblotting. Statistical analysis included partial least squares-discriminant analysis coupled with variable importance in projection identification. Results. Eighteen cirrhotic subjects were enrolled, and six healthy control subjects were extracted from our biorepository. Urine exosomes were isolated, and 1572 proteins were identified. Maltase-glucoamylase was the top discriminating protein confirmed by western blotting. Conclusions. Patients with cirrhosis and AKI have upregulation of renal brush border disaccharidase, MGAM, in urinary exosomes which may differentiate the type of kidney injury in cirrhosis; however, the clinical significance of this requires further validation.
url http://dx.doi.org/10.1155/2019/5912804
work_keys_str_mv AT lindaawdishu identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT shirleytsunoda identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT michellepearlman identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT chanthelkokoymondragon identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT majidghassemian identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT robertknaviaux identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT heathermpatton identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT ravindralmehta identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT bhavyavijay identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
AT satishpramachandrarao identificationofmaltaseglucoamylaseasabiomarkerofacutekidneyinjuryinpatientswithcirrhosis
_version_ 1725804577849081856