Published online Jul 6, 2016. doi: 10.5527/wjn.v5.i4.378
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
Processing time: 132 Days and 16.8 Hours
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.
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.