L’acidose pyroglutamique chez une patiente âgée

L’acidose pyroglutamique, initialement décrite dans la population pédiatrique chez des patients présentant des déficits enzymatiques innés, est une cause méconnue d’acidose métabolique à trou anionique augmenté (AMTAA) chez l’adulte (1). Cette forme acquise touche principalement les femmes présentant une pathologie chronique, souffrant de dénutrition et avec des antécédents d’utilisation chronique de paracétamol (2). Au cours des dernières années, plusieurs cas d’acidose pyroglutamique ont été rapportés suite à l’utilisation concomitante de paracétamol et de flucloxacilline (3,4). Nous rapportons ici le cas d’une patiente chez qui le diagnostic d’acidose pyroglutamique a été posé dans un contexte de traitement concomitant par paracétamol et flucloxacilline. Ce cas clinique reflète l’importance de considérer l’acidose pyroglutamique dans le diagnostic différentiel de l’AMTAA sans étiologie clairement identifiée, particulièrement en Gériatrie où les facteurs de risques sont fréquemment présents.[Pyroglutamic acidemia in an elderly patient] Pyroglutamic acidemia, initially described in the pediatric population due to inborn enzymatic deficiencies, is a relatively unknown cause of high anion gap metabolic acidosis (1). Acquired pyroglutamic acidemia is mostly diagnosed in malnourished women suffering from a chronic illness and with a history of chronic acetaminophen use (2). During the past decade, several cases of flucloxacillin- and paracetamol-induced pyroglutamic acidosis have been reported (3,4). We herein report a case of a patient diagnosed with pyroglutamic acidosis in the context of concomitant paracetamol and flucloxacillin treatment. This case report highlights the need to consider pyroglutamic acidosis in the differential diagnosis of high anion gap metabolic acidosis, given its reversibility under appropriate management

Sublethal effects of metal toxicity and the measure of plant fitness in ecotoxicological experiments

International audienceAnthropogenic pollution is a major driver of global environmental change. To be properly addressed, the study of the impact of pollutants must consider both lethal effects and sublethal effects on individual fitness. However, measuring fitness remains challenging. In plants, the total number of seeds produced, i.e. the seed set, is traditionally considered, but is not readily accessible. Instead, performance traits related to survival, e.g., vegetative biomass and reproductive success, can be measured, but their correlation with seed set has rarely been investigated. To develop accurate estimates of seed set, relationships among 15 vegetative and reproductive traits were analyzed. For this purpose, Noccaea caerulescens (Brassicaceae), a model plant to study local adaptation to metalcontaminated environments, was used. To investigate putative variation in trait relationships, sampling included several accessions cultivated in contrasting experimental conditions. To test their applicability, selected estimates were used in the first generation of a Laboratory Natural Selection (LNS) experiment exposing experimentally plants to zinc soil pollution. Principal component analyses revealed statistical independence between vegetative and reproductive traits. Traits showing the strongest positive correlation with seed set were the number of non-aborted silicles, and the product of this number and mean silicle length. They thus appeared the most appropriate to document sublethal or fitness effects of environmental contaminants in plant ecotoxicological studies. The relevance of both estimates was confirmed by using them to assess the fitness of parental plants of the first generation of an LNS experiment: the same families consistently displayed the highest or the lowest performance values in two independent experimental metal-exposed populations. Thus, both these fitness estimates could be used to determine the expected number of offspring and the composition of successive generations in further LNS experiments investigating the impact of multi-generational exposure of a plant species to environmental pollution

Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

International audienceBackground: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients

A low aromatic amino-acid diet improves renal function and prevents kidney fibrosis in mice with chronic kidney disease

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p-Cresyl glucuronide is a major metabolite of p-cresol in mouse: in contrast to p-cresyl sulphate, p-cresyl glucuronide fails to promote insulin resistance

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Revues de l’American Physical Society :la qualité pour un juste prix !

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A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease

International audienceAbstract Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition

p-Cresyl sulfate promotes insulin resistance associated with CKD.

International audienceThe mechanisms underlying the insulin resistance that frequently accompanies CKD are poorly understood, but the retention of renally excreted compounds may play a role. One such compound is p-cresyl sulfate (PCS), a protein-bound uremic toxin that originates from tyrosine metabolism by intestinal microbes. Here, we sought to determine whether PCS contributes to CKD-associated insulin resistance. Administering PCS to mice with normal kidney function for 4 weeks triggered insulin resistance, loss of fat mass, and ectopic redistribution of lipid in muscle and liver, mimicking features associated with CKD. Mice treated with PCS exhibited altered insulin signaling in skeletal muscle through ERK1/2 activation. In addition, exposing C2C12 myotubes to concentrations of PCS observed in CKD caused insulin resistance through direct activation of ERK1/2. Subtotal nephrectomy led to insulin resistance and dyslipidemia in mice, and treatment with the prebiotic arabino-xylo-oligosaccharide, which reduced serum PCS by decreasing intestinal production of p-cresol, prevented these metabolic derangements. Taken together, these data suggest that PCS contributes to insulin resistance and that targeting PCS may be a therapeutic strategy in CKD

Clinical management of the uraemic syndrome in chronic kidney disease

The clinical picture of the uraemic syndrome is a complex amalgam of accelerated ageing and organ dysfunction, which progress in parallel to chronic kidney disease. The uraemic syndrome is associated with cardiovascular disease, metabolic bone disease, inflammation, protein energy wasting, intestinal dysbiosis, anaemia, and neurological and endocrine dysfunction. In this Review, we summarise specific, modern management options for the uraemic syndrome in chronic kidney disease. Although large randomised controlled trials are scarce, based on data from randomised controlled trials and observational studies, as well as pathophysiological reasoning, a therapeutic algorithm can be developed for this complex and multifactorial condition, with interventions targeting several modifiable factors simultaneously