Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

Fernández-Prado, Raúl; Esteras, Raquel; Perez-Gomez, María Vanessa; Gracia-Iguacel, Carolina; González‐Parra, Emilio; Sanz, Ana B.; Ortíz, Alberto; Sanchez-Niño, María Dolores

doi:10.3390/nu9050489

Cited by 86 publications

(52 citation statements)

References 157 publications

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“…In the current study, supplementation for 24 weeks did not affect either the skeletal muscle strength or circulating markers in healthy women over 65 years of age. Positive and negative aspects of l -carnitine supplementation need to be clarified, especially considering its metabolite trimethylamino- N -oxide, which may be associated with the etiology of some diseases [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

et al. 2018

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Skeletal muscle wasting, associated with aging, may be regulated by the inflammatory cytokines as well as by insulin-like growth factor 1 (IGF-1). l-carnitine possesses anti-inflammatory properties and increases plasma IGF-1 concentration, leading to the regulation of the genes responsible for protein catabolism and anabolism. The purpose of the present study was to evaluate the effect of a 24-week l-carnitine supplementation on serum inflammatory markers, IGF-1, body composition and skeletal muscle strength in healthy human subjects over 65 years of age. Women between 65 and 70 years of age were supplemented for 24 weeks with either 1500 mg l-carnitine-l-tartrate or an isonitrogenous placebo per day in a double-blind fashion. Before and after the supplementation protocol, body mass and composition, as well as knee extensor and flexor muscle strength were determined. In the blood samples, free carnitine, interleukin-6, tumor necrosis factor-α, C-reactive protein and IGF-1 were determined. A marked increase in free plasma carnitine concentration was observed due to l-carnitine supplementation. No substantial changes in other parameters were noted. In the current study, supplementation for 24 weeks affected neither the skeletal muscle strength nor circulating markers in healthy women over 65 years of age. Positive and negative aspects of l-carnitine supplementation need to be clarified.

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Section: Discussionmentioning

confidence: 99%

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

et al. 2018

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“…This points towards major deficiencies in our understanding of the pathogenesis of CKD and of the pathophysiology of the CKD-associated increase in cardiovascular risk and premature aging. A key feature of advanced CKD is accumulation of uremic toxins that are no longer excreted by damaged kidneys, although in some instances increased toxin production also contributes to CKD manifestations [9][10][11]. However, this would not explain why there is already an increased risk of death when GFR is preserved, i.e., in patients in whom CKD is diagnosed because of abnormally high albuminuria yet GFR is still above 60 mL/min/1.73 m 2 .…”

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confidence: 99%

Chronodisruption: A Poorly Recognized Feature of CKD

Carriazo

Ramos

Sanz

et al. 2020

Toxins

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Multiple physiological variables change over time in a predictable and repetitive manner, guided by molecular clocks that respond to external and internal clues and are coordinated by a central clock. The kidney is the site of one of the most active peripheral clocks. Biological rhythms, of which the best known are circadian rhythms, are required for normal physiology of the kidneys and other organs. Chronodisruption refers to the chronic disruption of circadian rhythms leading to disease. While there is evidence that circadian rhythms may be altered in kidney disease and that altered circadian rhythms may accelerate chronic kidney disease (CKD) progression, there is no comprehensive review on chronodisruption and chronodisruptors in CKD and its manifestations. Indeed, the term chronodisruption has been rarely applied to CKD despite chronodisruptors being potential therapeutic targets in CKD patients. We now discuss evidence for chronodisruption in CKD and the impact of chronodisruption on CKD manifestations, identify potential chronodisruptors, some of them uremic toxins, and their therapeutic implications, and discuss current unanswered questions on this topic.

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“…Dietary Trp is metabolized by gut bacteria and the liver and incorporated into proteins and is excreted in urine as Trp metabolites. Gut bacteria Trp metabolism leads to the production of indole and IAA, which behave as or are precursors of uremic toxins [9,33]. Indole biosynthesis from dietary Trp is catalysed by a single-step reaction involving a specific Trpase (EC 4.1.99.1) [34].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients

Paats

Adoberg

Arund

et al. 2020

IJMS

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Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, −0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (−72%, −39%, −43%, respectively), serum tryptophan levels increased, resulting in negative RR (−8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.

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Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

Cited by 86 publications

References 157 publications

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

l-Carnitine Supplementation in Older Women. A Pilot Study on Aging Skeletal Muscle Mass and Function

Chronodisruption: A Poorly Recognized Feature of CKD

Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients

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