Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jul 6, 2016; 5(4): 378-388
Published online Jul 6, 2016. doi: 10.5527/wjn.v5.i4.378
Measurement of the intestinal permeability in chronic kidney disease
Matty L Terpstra, Ramandeep Singh, Suzanne E Geerlings, Frederike J Bemelman
Matty L Terpstra, Ramandeep Singh, Suzanne E Geerlings, Frederike J Bemelman, Division of Nephrology, Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands
Author contributions: Terpstra ML and Singh R performed the electronic search, all co-authors searched their own personal databases; Terpstra ML and Singh R independently screened all the articles for meeting the inclusion criteria; Bemelman FJ was consulted if there was discussion about inclusion; Terpstra ML extracted all data and wrote the paper under supervision of Geerlings SE and Bemelman FJ.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript. For this project no foundation or funding was received. For other non-related projects Bemelman FJ received a grant from Astellas Pharma. Geerlings SE is advisory consultant for InfectoPharm about fosfomycin iv.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Matty L Terpstra, MD, Division of Nephrology, Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Room number A3-273. P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. m.terpstra@amc.nl
Telephone: +31-20-5666135 Fax: +31-20-6972286
Received: February 17, 2016
Peer-review started: February 19, 2016
First decision: March 25, 2016
Revised: April 7, 2016
Accepted: June 14, 2016
Article in press: June 16, 2016
Published online: July 6, 2016
Abstract

AIM: To evaluate methods measuring the intestinal per-meability in chronic kidney disease (CKD) and clarify whether there is an increased intestinal permeability in CKD.

METHODS: We reviewed the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol and performed a systematic literature search through MEDline and EMBASE. All controlled trials and cohort studies using non-invasive methods to assess intestinal permeability in CKD patients were included. Excluded were: Conference abstracts and studies including patients younger than 18 years or animals. From the included studies we summarized the used methods and their advantages and disadvantages. For the comparison of their results we divided the included studies in two categories based on their included patient population, either assessing the intestinal permeability in mild to moderate CKD patients or in end stage renal disease (ESRD) patients. Results were graphically displayed in two plots, one comparing the intestinal permeability in mild to moderate CKD patients to healthy controls and one comparing the intestinal permeability in ESRD patients to healthy controls.

RESULTS: From the 480 identified reports, 15 met our inclusion criteria. Methods that were used to assess the intestinal permeability varied from markers measured in plasma to methods based on calculating the urinary excretion of an orally administered test substance. None of the applied methods has been validated in CKD patients and the influence of decreased renal function on the different methods remains unclear to a certain extent. Methods that seem the least likely to be influenced by decreased renal function are the quantitative PCR (qPCR) for bacterial DNA in blood and D-lactate. Considering the results published by the included studies; the studies including patients with mild to moderate CKD conducted conflicting results. Some studies did report an increase in intestinal permeability whilst other did not find a significant increased permeability. However, despite the variety in used methods among the different studies, all studies measuring the intestinal permeability in ESRD point out a significant increased intestinal permeability. Results should nevertheless be interpreted with caution due to the possible influence of a decreased glomerular filtration rate on test results.

CONCLUSION: The intestinal permeability in CKD: (1) could be measured by qPCR for bacterial DNA in blood and D-lactate; and (2) seems to be increased in ESRD.

Keywords: Chronic kidney disease, Intestinal barrier function, Intestinal permeability, Markers, Renal failure

Core tip: Several methods are currently being used to measure the intestinal permeability, there is however no gold standard. In addition to this, most methods are influenced by renal function. We suggest that preferred methods to assess the intestinal permeability in chronic kidney disease patients could be quantitative PCR for bacterial DNA in blood and D-lactate. Independent of the used method, all studies measuring the intestinal permeability in patients with end stage renal disease (ESRD) reported a significantly increased intestinal permeability. Even though these results should be interpret with caution due to the disadvantages of the applied methods, it seems likely that there is a connection between ESRD and intestinal barrier dysfunction.