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Toxins 2018, 10(5), 204; https://doi.org/10.3390/toxins10050204

Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease: Putative Role of Uremic Toxins

1
Univ. Lyon, CarMeN lab, INSERM U1060, INRA U1397, INSA de Lyon, Université Claude Bernard Lyon 1, F-69621 Villeurbanne, France
2
Department of Nephrology, Hospices Civils de Lyon, Hôpital Edouard Herriot, F-69437 Lyon, France
3
Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, F-69495 Pierre-Bénite, France
*
Author to whom correspondence should be addressed.
Received: 16 April 2018 / Revised: 10 May 2018 / Accepted: 15 May 2018 / Published: 16 May 2018
(This article belongs to the Special Issue The Intestine and Uremia)
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Abstract

Although gastrointestinal complications are a common feature of patients with chronic kidney disease (CKD), the impact of uremia on bowel motility remains poorly understood. The present study was, therefore, designed to investigate the impact of uremia on gut motility. Kidney failure was induced in mice by chemical nephrectomy using an adenine diet (0.25% w/w). Gastrointestinal transit time and colon motility were explored in vivo and ex vivo. Colons from control mice were incubated with uremic plasma or uremic toxins (urea, indoxyl-sulfate or p-cresyl-sulfate) at concentrations encountered in patients with end-stage renal disease. Mice fed an adenine diet for 3 weeks exhibited a 3-fold increase in plasma urea (p < 0.001) evidencing kidney failure. The median gastrointestinal transit time was doubled (1.8-fold, p < 0.001) while a reduction in colonic propulsive motility was observed in CKD mice (3-fold, p < 0.001). Colon from CKD mice exhibited an abnormal pattern of contraction associated with a blunted maximal force of contraction. Control colons incubated with plasma from hemodialysis patients exhibited a blunted level of maximal contraction (p < 0.01). Incubation with urea did not elicit any difference but incubation with indoxyl-sulfate or p-cresyl-sulfate decreased the maximal force of contraction (−66% and −55%, respectively. p < 0.01). Taken together, these data suggest that uremia impairs colon motility probably through the retention of uremic toxins. Colon dysmotility might contribute to the gastrointestinal symptoms often reported in patients with CKD. View Full-Text
Keywords: uremia; chronic kidney disease; gastrointestinal motility; colon; uremic toxins uremia; chronic kidney disease; gastrointestinal motility; colon; uremic toxins
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Hoibian, E.; Florens, N.; Koppe, L.; Vidal, H.; Soulage, C.O. Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease: Putative Role of Uremic Toxins. Toxins 2018, 10, 204.

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