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

Abstract

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. 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.

Gut-derived uremic toxin handling in vivo requires OAT-mediated tubular secretion in chronic kidney disease

“…Thus, it would seem that strategies aimed at limiting the generation of these uremic toxins early in the development of CKD could have beneficial effects, such as limiting the dietary source or treating with an intestinal absorbent such as AST-120 (51,(80)(81)(82). Moreover, since CKD and increasing levels of uremic toxins also can lead to gut dysbiosis (reflecting aberrant bidirectional interorganismal remote communication) and the generation of additional uremic solutes that could accelerate the progression of CKD (37,83), it is clear that limiting the accumulation of these uremic solutes/toxins early in the process could abort this vicious cycle and preserve residual tubular secretory activity.…”

Dietary Components That May Influence the Disturbed Gut Microbiota in Chronic Kidney Disease

“…It is important to consider that the benefits of the vegetable-based protein diet are probably related not only to protein but could be attributed to all other components of this dietary pattern. Despite the benefits associated with a vegetable-based protein diet, it is not yet known whether this diet pattern could promote more benefits to the gut microbiota than other patterns, and thereby perhaps render long-term health advantages to CKD patients [102,103]. The generation of uremic toxins is directly associated with the ratio of protein-to-carbohydrate intake because a high ratio favors the prevalence of proteolytic bacteria over saccharolytic species.…”

Very Low Protein Diet for Patients with Chronic Kidney Disease: Recent Insights

“…Several studies evidence the direct role of some uremic toxins, such as urea, trimetylamine N-oxyde, and p-cresol sulphate in glucose homeostasis alterations and incidence of diabetes [18,19]. A recent study showed that NT contributed to the insuline resistance reduction (estimated by the homeostatic model assessment-Homa-test) in 145 CKD patients with type 2 diabetes and a mean age of 65.5 ± 11.4 years.…”