Experimental studies of small intestinal permeability and function in uremia

• The intestinal permeability has been investigated in experimental chronic and acute uremia in rats. The permeability and the mucosal ability to exclude larger molecules have been measured using differently sized polyethylene glycols (PEG 400 and 1000: mean weights of 400 and 1000 dalton, range 326-1162 dalton). The permeation (uptake) of the differently sized molecules has been estimated from the urinary recovery of the PEGs after oral administration of the permeability markers. The effects of two different diets (high-and low-protein) have been studied inexperimental chronic uremia and in normal rats. The renal excretion of the PEGs after intravenous administration has also been investigated in chronic uremic rats. Furthermore, the effect of experimental acute uremia on intestinal brush border peptidases, disaccharidases and mucosal morphology have been studied. Finally has the urinary recovery of PEGs been investigated in patients with renal insufficiency compared to healthy subjects.The urinary recovery of PEGs was reduced after intravenous administration in chronic uremic rats. The relative excretion of the smaller PEGs was, however, increased compared to the larger ones in the uremic rats. The opposite was found in the control rats. Intestinal permeability, measured as an increased urinary recovery after oral administration of larger PEGs, was increased in chrortic uremic rats.The overall urinary recovery of the PEG molecules was reduced in patients with renal insufficiency. However, the relative excretion of the differently sized PEGs indicated a relative increased uptake of larger molecules also in uremic patients suggesting a more permeable gut.An opposite pattern was seen in experimental acute uremic rats, reduced urinary recovery along with a relative decreased excretion of larger molecules compatible with a less permeable gut.Moreover, both in the chronic uremic and in the control rats treated with low-protein diet was a reduction of intestinal permeability seen.Increased activity of brush border peptidases was found in acute uremic rats. Minor morphological changes, shortening of the microvilli of the enterocytes in the small intestine were also observed. On the other hand, no alterations of the disaccharidases were measured.In conclusion, the change in intestinal permeability indicates a more leaky mucosal barrier in chronic uremia. Functional alterations i.e. increased peptidase activity was seen in acute uremic rats. A more leaky gut might allow potentially toxic, infectious and immunogenic substances to pass more freely over the mucosa in chronic uremia.

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