Measurement of the intestinal permeability in chronic kidney disease

Table 1 Characteristics of the used methods assessing the intestinal permeability

Marker for intestinal permeability	Mechanism of action	Advantages	Disadvantages	Influence renal function	Part of the intestine evaluated	Ref.
D-lactate (plasma)	Produced by bacteria in the colon. Present in human blood at very low concentrations as a product of methylglyoxal metabolism. In case of increased intestinal permeability levels will rise due to increased translocation across the intestinal mucosa	Non-invasive Low levels in healthy subjects, high specificity Mainly large intestine; thus focusing on part of the bowel with the highest bacterial load	Possibly increased fermentation of undigested carbohydrates to D-lactate in case of bacterial overgrowth	Influenced by renal function to some extent	Mainly large intestine	[18,19]
Sugar absorption test (urine)	Method based on calculating the urinary excretion of orally administered test substance that reflects the non-mediated diffusion of that probe across the intestinal barrier. Most commonly used combination of sugars is a oligosaccharide or disaccharide (lactulose, cellobiose) combined with a monosaccharide (mannitol). By adding sucralose to the test, which is not degraded by the bacteria of the colon, the colonic permeability can be assessed	Non-invasive Different sugar combinations can assess different parts of the gastrointestinal tract	Relative impractical in use Results could be influenced by decreased bowel motility 32 Used according to different protocols and different combinations of sugars which makes the comparison of studies difficult Relative large inter- and intra-individual variety	Influenced by renal function. Corrected by using the ratio of administered sugars. It is however not clarified whether this correction is sufficient due to possible different renal clearance of the administered sugars	Small intestine, large intestine (only if sucralose, is added)	[14-17]
5¹Cr-EDTA (urine)	Method based on calculating the urinary excretion of orally administered test substance that reflects the non-mediated diffusion of that probe across the intestinal barrier	Not degraded by bacteria in the colon, useful marker for both the small and large intestinal permeability	Radioactivity Not commonly used nowadays due to radioactivity	Influenced by renal function. Corrected in included studies: 24-h Cr-EDTA excretion = 100% of the total oral dose excreted in the urine in 24 h/creatinine	Both small and large intestine	[20-23]
Endotoxin level (blood), LPS (plasma)	Indirect measurement of translocation of bacterial products	High specificity	Not eligible to use among patients with inflammation in the GI tract	Unlikely to be influenced by renal function	Both small and large intestine	[18,25,26]
Bacterial derived DNA (16S rRNA PCR) (blood)	Direct measurement of bacterial products in blood	Optimal tool for detection and identification of bacterial isolates	Not eligible to use among patients with inflammation in the GI tract	Unlikely to be influenced by renal function	Both small and large intestine	[18,19,24]
Polyethylene glycols (PEG) (urine)	Method based on calculating the urinary excretion of orally administered test substance that reflects the non-mediated diffusion of that probe across the intestinal barrier. It is hypothesized that, as saccharides in sugar absorption test, molecular PEG will only cross the intestinal mucosa to the circulation in case of barrier integrity loss. Increased urinary levels of large PEGs therefore reflect an increased intestinal permeability	Biologically inert and not degraded by bacteria, thus providing information of the whole intestinal permeability	High inter- and intra-individual variations have been reported, even in healthy controls[34]	Influenced by renal function	Both small and large intestine	[28]

AVF: Arteriovenous fistula; CAPD: Continuous ambulatory peritoneal dialysis; CKD: Chronic kidney disease; CVC: Central venous catheter; ESRD: End stage renal disease; HD: Hemodialysis; IgAN: IgA nephropathy; IgA GN: IgA glomerulonephritis; IC-GN: Immunocomplex glomerulonephritis; INS: Idiopathic nephrotic syndrome; Li: Lithium; LPS: Lipopolysaccharide; PD: Peritoneal dialysis; PEG: Polyethylene glycols; TER: Trans epithelial electrical resistance.