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Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins

  • Microvascular Complications—Nephropathy (M Afkarian and B Roshanravan, Section Editors)
  • Published:
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Abstract

Purpose of Review

Chronic kidney disease (CKD) is characterized by the accumulation of uremic retention solutes (URS) and is associated with perturbations of glucose homeostasis even in absence of diabetes. The underlying mechanisms of insulin resistance, β cell failure, and increase risk of diabetes in CKD, however, remain unclear. Metabolomic studies reported that some metabolites are similar in CKD and diabetic kidney disease (DKD) and contribute to the progression to end-stage renal disease. We attempted to discuss the mechanisms involved in the disruption of carbohydrate metabolism in CKD by focusing on the specific role of URS.

Recent Findings

Recent clinical data have demonstrated a defect of insulin secretion in CKD. Several studies highlighted the direct role of some URS (urea, trimethylamine N-oxide (TMAO), p-cresyl sulfate, 3-carboxylic acid 4-methyl-5-propyl-2-furan propionic (CMPF)) in glucose homeostasis abnormalities and diabetes incidence.

Summary

Gut dysbiosis has been identified as a potential contributor to diabetes and to the production of URS. The complex interplay between the gut microbiota, kidney, pancreas β cell, and peripheral insulin target tissues has brought out new hypotheses for the pathogenesis of CKD and DKD. The characterization of intestinal microbiota and its associated metabolites are likely to fill fundamental knowledge gaps leading to innovative research, clinical trials, and new treatments for CKD and DKD.

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Authors and Affiliations

  1. Department Nephrology, Centre Hospitalier Lyon Sud, 69495, Pierre-Benite, France

    Laetitia Koppe & Denis Fouque

  2. Univ. Lyon, CarMeN lab, INSA-Lyon, INSERM U1060, INRA, Université Claude Bernard Lyon 1, 69621, Villeurbanne, France

    Laetitia Koppe, Denis Fouque & Christophe O. Soulage

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  1. Laetitia Koppe
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  2. Denis Fouque
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Correspondence to Laetitia Koppe.

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L. Koppe and C.O. Soulage declare that they have no conflict of interest.

D. Fouque received honoraria and travel support from Fresenius Kabi, which markets a ketoanalogue supplement.

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This article is part of the Topical Collection on Microvascular Complications—Nephropathy

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Koppe, L., Fouque, D. & Soulage, C.O. Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins. Curr Diab Rep 18, 97 (2018). https://doi.org/10.1007/s11892-018-1064-7

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