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Dr. Laetitia KOPPE
Department of Nephrology, Centre Hospitalier Lyon Sud, Cardiovascular, Metabolism, Diabetology and Nutrition (CarMeN) Lab, European Center for Nutrition and Health (CENS), University of Lyon, Lyon, France

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Research Keywords & Expertise

0 Chronic Kidney Disease
0 Inflammation
0 Insulin Resistance
0 Urea
0 sarcopenia

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Chronic Kidney Disease
uremic toxins
Insulin Resistance
intestinal microbiota
P-cresyl sulfate
Protein energy wasting and malnutrition
Inflammation
Urea
Indoxyl sulfate
glucose homeostasis
Beta cell and insulin secretion

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Preprint content
Published: 03 June 2021
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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 uremic toxins production, with a lower risk of malnutrition.

ACS Style

Christophe Barba; Bérengère Benoit; Bres Emilie; Stéphanie Chanon; Aurélie Vieille-Marchiset; Claudie Pinteur; Sandra Pesenti; Griet Glorieux; Cécile Picard; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. A Low Aromatic Amino-Acid Diet Improves Renal Function and Prevent Kidney Fibrosis in Mice with Chronic Kidney Disease. 2021, 1 .

AMA Style

Christophe Barba, Bérengère Benoit, Bres Emilie, Stéphanie Chanon, Aurélie Vieille-Marchiset, Claudie Pinteur, Sandra Pesenti, Griet Glorieux, Cécile Picard, Denis Fouque, Christophe O. Soulage, Laetitia Koppe. A Low Aromatic Amino-Acid Diet Improves Renal Function and Prevent Kidney Fibrosis in Mice with Chronic Kidney Disease. . 2021; ():1.

Chicago/Turabian Style

Christophe Barba; Bérengère Benoit; Bres Emilie; Stéphanie Chanon; Aurélie Vieille-Marchiset; Claudie Pinteur; Sandra Pesenti; Griet Glorieux; Cécile Picard; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. 2021. "A Low Aromatic Amino-Acid Diet Improves Renal Function and Prevent Kidney Fibrosis in Mice with Chronic Kidney Disease." , no. : 1.

Journal article
Published: 01 April 2021 in Journal of Renal Nutrition
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Objective Imbalance between anabolism and catabolism is linked to cachexia and protein-energy wasting (PEW), especially in frail populations such as patients with chronic kidney disease. PEW is responsible of poor outcomes with increased morbidity and mortality. Several causes are involved in PEW such as insulin resistance, acidosis, or hyperparathyroidism. Natriuretic peptides (NPs) have recently been described as activators of resting energy expenditure through the induction of browning of white adipose tissue in rodents with chronic kidney disease. The present study was therefore implemented to investigate whether NPs could be associated with PEW criteria and predict clinical outcomes. Methods We quantified serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) in a prospective cohort of 231 patients undergoing maintenance hemodialysis and atrial natriuretic peptide in a subgroup of 35 patients. Body composition parameters were measured with bioimpedance spectroscopy. Results NT-proBNP was inversely associated with serum albumin, prealbumin, and body mass index and, conversely, positively associated with age and C-reactive protein. NT-proBNP as well as atrial natriuretic peptide were significantly higher in patients with PEW criteria. NT-proBNP was negatively associated with body fat mass. In multiple linear regression, NT-proBNP remained associated with body mass index. Kaplan-Meier analysis revealed a significant correlation between serum NT-proBNP concentrations and all-cause mortality and cardiovascular events. This association remained significant after multivariable Cox regression models adjusted for demographic factors and cardiovascular risk factors. Conclusion Accumulation of NPs seems to be associated with poor nutritional status and reduced survival among hemodialysis patients. Further studies are needed to confirm this association using resting energy expenditure measurement and adipose tissue biopsy.

ACS Style

Mathilde Luce; Emilie Bres; Dan Yi; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouche; Anais Bouchara; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. Natriuretic Peptides as Predictors of Protein-Energy Wasting in Hemodialysis Population. Journal of Renal Nutrition 2021, 1 .

AMA Style

Mathilde Luce, Emilie Bres, Dan Yi, Myriam Pastural, Samuel Granjon, Jean Christophe Szelag, Maurice Laville, Walid Arkouche, Anais Bouchara, Denis Fouque, Christophe O. Soulage, Laetitia Koppe. Natriuretic Peptides as Predictors of Protein-Energy Wasting in Hemodialysis Population. Journal of Renal Nutrition. 2021; ():1.

Chicago/Turabian Style

Mathilde Luce; Emilie Bres; Dan Yi; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouche; Anais Bouchara; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. 2021. "Natriuretic Peptides as Predictors of Protein-Energy Wasting in Hemodialysis Population." Journal of Renal Nutrition , no. : 1.

Accepted manuscript
Published: 10 February 2021 in Nephrology Dialysis Transplantation
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ACS Style

Laetitia Koppe; Srinivasan Beddhu; Philippe Chauveau; Csaba P Kovesdy; Denise Mafra; Shivam Joshi; Kamyar Kalantar-Zadeh; Denis Fouque. A call for a better understanding of the role of dietary amino acids and post-translational protein modifications of the microbiome in the progression of CKD. Nephrology Dialysis Transplantation 2021, 36, 1357 -1360.

AMA Style

Laetitia Koppe, Srinivasan Beddhu, Philippe Chauveau, Csaba P Kovesdy, Denise Mafra, Shivam Joshi, Kamyar Kalantar-Zadeh, Denis Fouque. A call for a better understanding of the role of dietary amino acids and post-translational protein modifications of the microbiome in the progression of CKD. Nephrology Dialysis Transplantation. 2021; 36 (8):1357-1360.

Chicago/Turabian Style

Laetitia Koppe; Srinivasan Beddhu; Philippe Chauveau; Csaba P Kovesdy; Denise Mafra; Shivam Joshi; Kamyar Kalantar-Zadeh; Denis Fouque. 2021. "A call for a better understanding of the role of dietary amino acids and post-translational protein modifications of the microbiome in the progression of CKD." Nephrology Dialysis Transplantation 36, no. 8: 1357-1360.

Review
Published: 19 December 2020 in Nutrients
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Nutrition is a cornerstone in the management of chronic kidney disease (CKD). To limit urea generation and accumulation, a global reduction in protein intake is routinely proposed. However, recent evidence has accumulated on the benefits of plant-based diets and plant-derived proteins without a clear understanding of underlying mechanisms. Particularly the roles of some amino acids (AAs) appear to be either deleterious or beneficial on the progression of CKD and its complications. This review outlines recent data on the role of a low protein intake, the plant nature of proteins, and some specific AAs actions on kidney function and metabolic disorders. We will focus on renal hemodynamics, intestinal microbiota, and the production of uremic toxins. Overall, these mechanistic effects are still poorly understood but deserve special attention to understand why low-protein diets provide clinical benefits and to find potential new therapeutic targets in CKD.

ACS Style

Pierre Letourneau; Stanislas Bataille; Philippe Chauveau; Denis Fouque; Laetitia Koppe. Source and Composition in Amino Acid of Dietary Proteins in the Primary Prevention and Treatment of CKD. Nutrients 2020, 12, 3892 .

AMA Style

Pierre Letourneau, Stanislas Bataille, Philippe Chauveau, Denis Fouque, Laetitia Koppe. Source and Composition in Amino Acid of Dietary Proteins in the Primary Prevention and Treatment of CKD. Nutrients. 2020; 12 (12):3892.

Chicago/Turabian Style

Pierre Letourneau; Stanislas Bataille; Philippe Chauveau; Denis Fouque; Laetitia Koppe. 2020. "Source and Composition in Amino Acid of Dietary Proteins in the Primary Prevention and Treatment of CKD." Nutrients 12, no. 12: 3892.

Journal article
Published: 24 November 2020 in Toxins
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Background: 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.

ACS Style

Christophe Barba; Christophe O. Soulage; Gianvito Caggiano; Griet Glorieux; Denis Fouque; Laetitia Koppe. Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD. Toxins 2020, 12, 741 .

AMA Style

Christophe Barba, Christophe O. Soulage, Gianvito Caggiano, Griet Glorieux, Denis Fouque, Laetitia Koppe. Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD. Toxins. 2020; 12 (12):741.

Chicago/Turabian Style

Christophe Barba; Christophe O. Soulage; Gianvito Caggiano; Griet Glorieux; Denis Fouque; Laetitia Koppe. 2020. "Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD." Toxins 12, no. 12: 741.

Journal article
Published: 14 May 2020 in Clinical Kidney Journal
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Background Kidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations. Methods Forty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund–Malmö equations were compared with reference methods (inulin or iohexol clearance). Results The mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was −1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy. Conclusions Patients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.

ACS Style

Elodie Chalencon; Laetitia Koppe; Madeleine Lauverjat; Didier Barnoud; Denis Fouque; Cécile Chambrier. Evolution of renal function in patients with severe intestinal failure on home parenteral nutrition. Clinical Kidney Journal 2020, 14, 925 -932.

AMA Style

Elodie Chalencon, Laetitia Koppe, Madeleine Lauverjat, Didier Barnoud, Denis Fouque, Cécile Chambrier. Evolution of renal function in patients with severe intestinal failure on home parenteral nutrition. Clinical Kidney Journal. 2020; 14 (3):925-932.

Chicago/Turabian Style

Elodie Chalencon; Laetitia Koppe; Madeleine Lauverjat; Didier Barnoud; Denis Fouque; Cécile Chambrier. 2020. "Evolution of renal function in patients with severe intestinal failure on home parenteral nutrition." Clinical Kidney Journal 14, no. 3: 925-932.

Review
Published: 06 May 2020 in Toxins
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Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.

ACS Style

Maxime Espi; Laetitia Koppe; Denis Fouque; Olivier Thaunat. Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins 2020, 12, 300 .

AMA Style

Maxime Espi, Laetitia Koppe, Denis Fouque, Olivier Thaunat. Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins. 2020; 12 (5):300.

Chicago/Turabian Style

Maxime Espi; Laetitia Koppe; Denis Fouque; Olivier Thaunat. 2020. "Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells." Toxins 12, no. 5: 300.

Review
Published: 03 September 2019 in Nutrients
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Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.

ACS Style

Laetitia Koppe; Mariana Cassani De Oliveira; Denis Fouque. Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives. Nutrients 2019, 11, 2071 .

AMA Style

Laetitia Koppe, Mariana Cassani De Oliveira, Denis Fouque. Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives. Nutrients. 2019; 11 (9):2071.

Chicago/Turabian Style

Laetitia Koppe; Mariana Cassani De Oliveira; Denis Fouque. 2019. "Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives." Nutrients 11, no. 9: 2071.

Comment
Published: 05 July 2019 in Nephrology Dialysis Transplantation
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ACS Style

Emilie Bres; Laetitia Koppe. Is there still a place for prebiotics in chronic kidney disease? Nephrology Dialysis Transplantation 2019, 34, 1812 -1816.

AMA Style

Emilie Bres, Laetitia Koppe. Is there still a place for prebiotics in chronic kidney disease? Nephrology Dialysis Transplantation. 2019; 34 (11):1812-1816.

Chicago/Turabian Style

Emilie Bres; Laetitia Koppe. 2019. "Is there still a place for prebiotics in chronic kidney disease?" Nephrology Dialysis Transplantation 34, no. 11: 1812-1816.

Editorial
Published: 12 April 2019 in Journal of Cachexia, Sarcopenia and Muscle
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Weight loss and homeostatic disturbances of both energy and protein balances are characteristics of several illnesses including cancer, heart failure, and chronic kidney disease (CKD). Different definitions have been used to describe this deleterious process. The term protein‐energy wasting (PEW) has been proposed for CKD patients by the International Society of Renal Nutrition and Metabolism. Since its inception, the term PEW has been exceptionally successful, highlighted by 327 original publications referenced in PubMed over 10 years. Using this classification, several studies have confirmed that PEW is among the strongest predictors of mortality in CKD patients [hazard ratio of 3.03; confidence interval of 1.69–5.26 in 1068 haemodialysis patients and 1.40 (1.04–1.89) in 1487 non‐dialysed patients across PEW stages 0 to 4]. Based on this classification, prevalence of PEW is 28% to 54% among 16 434 adults undergoing maintenance dialysis. PEW prevalence increases when renal function declines, that is, from 5% is a mandatory criterion for cachexia but only supportive for PEW. The recent understanding of cachexia physiopathology during CKD progression suggests that PEW and cachexia are closely related and that PEW corresponds to the initial state of a continuous process that leads to cachexia, implicating the same metabolic pathways as in other chronic diseases. Despite the success of the definition of PEW, using a more uniform term such as ‘kidney disease cachexia’ could be more helpful to design future research through collaborative groups of researchers with focus on cachexia.

ACS Style

Laetitia Koppe; Denis Fouque; Kamyar Kalantar-Zadeh. Kidney cachexia or protein‐energy wasting in chronic kidney disease: facts and numbers. Journal of Cachexia, Sarcopenia and Muscle 2019, 10, 479 -484.

AMA Style

Laetitia Koppe, Denis Fouque, Kamyar Kalantar-Zadeh. Kidney cachexia or protein‐energy wasting in chronic kidney disease: facts and numbers. Journal of Cachexia, Sarcopenia and Muscle. 2019; 10 (3):479-484.

Chicago/Turabian Style

Laetitia Koppe; Denis Fouque; Kamyar Kalantar-Zadeh. 2019. "Kidney cachexia or protein‐energy wasting in chronic kidney disease: facts and numbers." Journal of Cachexia, Sarcopenia and Muscle 10, no. 3: 479-484.

Review
Published: 01 March 2019 in Kidney International
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The past two decades have witnessed tremendous progress in our understanding of the mechanisms underlying wasting and cachexia in chronic kidney disease (CKD) and in other chronic illnesses, such as cancer and heart failure. In all these conditions wasting is an effect of the activation of protein degradation in muscle, a response that increases the risk of morbidity and mortality. Major recent advances in our knowledge on how CKD and inflammation affect cellular signaling include the identification of the myostatin (MSTN)/activin system, and its related transcriptional program that promotes protein degradation. In addition, the identification of the role of MSTN/activin in the vascular wall shows premise that its inhibition can better control or prevent some effects of CKD on vessels, such as accelerated atherosclerosis and vascular calcifications. In this review, we summarize the expanding role of MSTN activation in promoting muscle atrophy and the recent clinical studies that investigated the efficacy of MSTN/activin pathway antagonism in sarcopenic patients. Moreover, we also review the utility of MSTN inhibition in the experimental models of CKD and its potential advantages in CKD patients. Lessons learned from clinical studies on MSTN antagonism in sarcopenic patients tell us that the anabolic intervention is likely better if we use a block of the two ActRII receptors. At the same time, however, it is becoming clear that MSTN-targeted therapies should not be seen as a substitute for physical activity and nutritional supplementation which are mandatory to successfully manage patients with wasting.

ACS Style

Daniela Verzola; Chiara Barisione; Daniela Picciotto; Giacomo Garibotto; Laetitia Koppe. Emerging role of myostatin and its inhibition in the setting of chronic kidney disease. Kidney International 2019, 95, 506 -517.

AMA Style

Daniela Verzola, Chiara Barisione, Daniela Picciotto, Giacomo Garibotto, Laetitia Koppe. Emerging role of myostatin and its inhibition in the setting of chronic kidney disease. Kidney International. 2019; 95 (3):506-517.

Chicago/Turabian Style

Daniela Verzola; Chiara Barisione; Daniela Picciotto; Giacomo Garibotto; Laetitia Koppe. 2019. "Emerging role of myostatin and its inhibition in the setting of chronic kidney disease." Kidney International 95, no. 3: 506-517.

Journal article
Published: 01 November 2018 in Kidney International
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Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

ACS Style

Anaïs Bouchara; Dan Yi; Myriam Pastural; Samuel Granjon; Jean-Christophe Selag; Maurice Laville; Walid Arkouche; Solenne Pelletier; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients. Kidney International 2018, 94, 983 -992.

AMA Style

Anaïs Bouchara, Dan Yi, Myriam Pastural, Samuel Granjon, Jean-Christophe Selag, Maurice Laville, Walid Arkouche, Solenne Pelletier, Denis Fouque, Christophe O. Soulage, Laetitia Koppe. Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients. Kidney International. 2018; 94 (5):983-992.

Chicago/Turabian Style

Anaïs Bouchara; Dan Yi; Myriam Pastural; Samuel Granjon; Jean-Christophe Selag; Maurice Laville; Walid Arkouche; Solenne Pelletier; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. 2018. "Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients." Kidney International 94, no. 5: 983-992.

Review
Published: 08 September 2018 in Current Diabetes Reports
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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 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.

ACS Style

Laetitia Koppe; Denis Fouque; Christophe O. Soulage. Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins. Current Diabetes Reports 2018, 18, 97 .

AMA Style

Laetitia Koppe, Denis Fouque, Christophe O. Soulage. Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins. Current Diabetes Reports. 2018; 18 (10):97.

Chicago/Turabian Style

Laetitia Koppe; Denis Fouque; Christophe O. Soulage. 2018. "Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins." Current Diabetes Reports 18, no. 10: 97.

Journal article
Published: 18 May 2018 in Toxins
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3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) is a metabolite of furan fatty acid and a marker of fish oil intake. CMPF is described as a protein-bound uremic toxin and interacts with free oxygen radicals, which can induce cell damages. However, the clinical consequences of CMPF accumulation in haemodialysis patients remain poorly documented. The aims of this study are to investigate potential association between CMPF levels and (i) biochemical and nutritional parameters; (ii) cardiovascular events and (iii) mortality. Two hundred and fifty-two patients undergoing maintenance haemodialysis were included. Routine clinical biochemistry tests and assay for CMPF by HPLC technique were performed at the inclusion. Body composition parameters were measured using a bioimpedance spectroscopy method. The enrolled patients were prospectively monitored for cardiovascular events and mortality. CMPF level was positively correlated with nutritional parameters and lean mass and is significantly higher in patients without protein-energy wasting. However, the multivariate linear regression analysis indicated that CMPF level was not independently associated with albumin, prealbumin, creatinemia and body mass index. Elevated serum CMPF was not associated with mortality and cardiovascular morbidity. Our results indicate that CMPF is not a relevant uremic toxin in haemodialysis and in contrast could be a marker of healthy diet and omega 3 intakes.

ACS Style

Mathilde Luce; Anais Bouchara; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouche; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. Is 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) a Clinically Relevant Uremic Toxin in Haemodialysis Patients? Toxins 2018, 10, 205 .

AMA Style

Mathilde Luce, Anais Bouchara, Myriam Pastural, Samuel Granjon, Jean Christophe Szelag, Maurice Laville, Walid Arkouche, Denis Fouque, Christophe O. Soulage, Laetitia Koppe. Is 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) a Clinically Relevant Uremic Toxin in Haemodialysis Patients? Toxins. 2018; 10 (5):205.

Chicago/Turabian Style

Mathilde Luce; Anais Bouchara; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouche; Denis Fouque; Christophe O. Soulage; Laetitia Koppe. 2018. "Is 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) a Clinically Relevant Uremic Toxin in Haemodialysis Patients?" Toxins 10, no. 5: 205.

Journal article
Published: 16 May 2018 in Toxins
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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.

ACS Style

Elsa Hoibian; Nans Florens; Laetitia Koppe; Hubert Vidal; Christophe O. Soulage. Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease: Putative Role of Uremic Toxins. Toxins 2018, 10, 204 .

AMA Style

Elsa Hoibian, Nans Florens, Laetitia Koppe, Hubert Vidal, Christophe O. Soulage. Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease: Putative Role of Uremic Toxins. Toxins. 2018; 10 (5):204.

Chicago/Turabian Style

Elsa Hoibian; Nans Florens; Laetitia Koppe; Hubert Vidal; Christophe O. Soulage. 2018. "Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease: Putative Role of Uremic Toxins." Toxins 10, no. 5: 204.

Journal article
Published: 01 May 2018 in Nephrology Dialysis Transplantation
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INTRODUCTION AND AIMS: In patients with chronic kidney disease (CKD), protein energy wasting (PEW) is characterized by an increased resting energy expenditure (REE) although the underlying mechanisms remain poorly understood. Browning corresponds to the activation of inducible brown adipocytes in white adipose tissue (WAT) and participates in cachexia associated with hypermetabolic diseases such as cancers. The objective of this study was to highlight a phenomenon of browning associated with CKD and to study the potential role of uremic environment in the activation of this phenomenon.

ACS Style

Mathilde Luce; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouch; Denis Fouque; Christophe O Soulage; Laetitia Koppe. SaO045ACTIVATION OF BROWNING IN WHITE ADIPOSE TISSUE DURING CHRONIC KIDNEY DISEASE. Nephrology Dialysis Transplantation 2018, 33, i334 -i334.

AMA Style

Mathilde Luce, Myriam Pastural, Samuel Granjon, Jean Christophe Szelag, Maurice Laville, Walid Arkouch, Denis Fouque, Christophe O Soulage, Laetitia Koppe. SaO045ACTIVATION OF BROWNING IN WHITE ADIPOSE TISSUE DURING CHRONIC KIDNEY DISEASE. Nephrology Dialysis Transplantation. 2018; 33 (suppl_1):i334-i334.

Chicago/Turabian Style

Mathilde Luce; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouch; Denis Fouque; Christophe O Soulage; Laetitia Koppe. 2018. "SaO045ACTIVATION OF BROWNING IN WHITE ADIPOSE TISSUE DURING CHRONIC KIDNEY DISEASE." Nephrology Dialysis Transplantation 33, no. suppl_1: i334-i334.

Journal article
Published: 01 May 2018 in Nephrology Dialysis Transplantation
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INTRODUCTION AND AIMS: Chronic kidney disease (CKD) is characterized by accumulation of uremic toxins especially, some protein-bound uremic toxins as p-cresyl sulfate which are considered to be associated with an increase of cardiovascular (CV) disease and mortality. 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) is a metabolite of furan fatty acid and is increased in patients consuming fish or fish oil. Blood CMPF is known to be elevated in CKD and it is poorly removed by haemodialysis (HD). CMPF directly interacts with free oxygen radicals, which can induce cell damages. Therefore, CMPF has been reported to inhibit erythropoiesis, contributes to the development of thyroid abnormalities and impair neurological function. The putative role of CMPF in beta-cell dysfunction and metabolic syndrome is still under debate. The aim of the present study is to investigate potential association between CMPF levels and i) biochemical and nutritional parameters that are disturbed in HD, (ii) CV events and (iii) mortality.

ACS Style

Mathilde Luce; Anaïs Bouchara; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouch; Denis Fouque; Christophe O Soulage; Laetitia Koppe. FP322THE UREMIC TOXIN 3 CARBOXY 4 METHYL 5 PROPYL 2 FURANPROPANOIC ACID (CMPF): PARADOX OF ANEW NUTRITIONAL MARKER IN HAEMODIALYSIS. Nephrology Dialysis Transplantation 2018, 33, i139 -i139.

AMA Style

Mathilde Luce, Anaïs Bouchara, Myriam Pastural, Samuel Granjon, Jean Christophe Szelag, Maurice Laville, Walid Arkouch, Denis Fouque, Christophe O Soulage, Laetitia Koppe. FP322THE UREMIC TOXIN 3 CARBOXY 4 METHYL 5 PROPYL 2 FURANPROPANOIC ACID (CMPF): PARADOX OF ANEW NUTRITIONAL MARKER IN HAEMODIALYSIS. Nephrology Dialysis Transplantation. 2018; 33 (suppl_1):i139-i139.

Chicago/Turabian Style

Mathilde Luce; Anaïs Bouchara; Myriam Pastural; Samuel Granjon; Jean Christophe Szelag; Maurice Laville; Walid Arkouch; Denis Fouque; Christophe O Soulage; Laetitia Koppe. 2018. "FP322THE UREMIC TOXIN 3 CARBOXY 4 METHYL 5 PROPYL 2 FURANPROPANOIC ACID (CMPF): PARADOX OF ANEW NUTRITIONAL MARKER IN HAEMODIALYSIS." Nephrology Dialysis Transplantation 33, no. suppl_1: i139-i139.

Review
Published: 13 April 2018 in Toxins
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Uremic retention solutes (URS) are associated with cardiovascular complications and poor survival in chronic kidney disease. The better understanding of the origin of a certain number of these toxins enabled the development of new strategies to reduce their production. URS can be classified according to their origins (i.e., host, microbial, or exogenous). The discovery of the fundamental role that the intestinal microbiota plays in the production of many URS has reinstated nutrition at the heart of therapeutics to prevent the accumulation of URS and their deleterious effects. The intestinal microbiota is personalized and is strongly influenced by dietary habits, such as the quantity and the quality of dietary protein and fibers. Herein, this review out lines the role of intestinal microbiota on URS production and the recent discoveries on the effect of diet composition on the microbial balance in the host with a focus on the effect on URS production.

ACS Style

Laetitia Koppe; Denis Fouque; Christophe O. Soulage. The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease. Toxins 2018, 10, 155 .

AMA Style

Laetitia Koppe, Denis Fouque, Christophe O. Soulage. The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease. Toxins. 2018; 10 (4):155.

Chicago/Turabian Style

Laetitia Koppe; Denis Fouque; Christophe O. Soulage. 2018. "The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease." Toxins 10, no. 4: 155.

Journal article
Published: 03 August 2017 in Nephrology Dialysis Transplantation
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The role of uraemic toxins in insulin resistance associated with chronic kidney disease (CKD) is gaining interest. p-Cresol has been defined as the intestinally generated precursor of the prototype protein-bound uraemic toxins p-cresyl sulphate (p-CS) as the main metabolite and, at a markedly lower concentration in humans, p-cresyl glucuronide (p-CG). The objective of the present study was to evaluate the metabolism of p-cresol in mice and to decipher the potential role of both conjugates of p-cresol on glucose metabolism. p-CS and p-CG were measured by high performance liquid chromatography-fluorescence in serum from control, 5/6 nephrectomized mice and mice injected intraperitoneously with either p-cresol or p-CG. The insulin sensitivity in vivo was estimated by insulin tolerance test. The insulin pathway in the presence of p-cresol, p-CG and/or p-CS was further evaluated in vitro on C2C12 muscle cells by measuring insulin-stimulated glucose uptake and the insulin signalling pathway (protein kinase B, PKB/Akt) by western blot. In contrast to in humans, where p-CS is the main metabolite of p-cresol, in CKD mice both conjugates accumulated, and after chronic p-cresol administration with equivalent concentrations but a substantial difference in protein binding (96% for p-CS and <6% for p-CG). p-CG exhibited no effect on insulin sensitivity in vivo or in vitro and no synergistic inhibiting effect in combination with p-CS. The relative proportion of the two p-cresol conjugates, i.e. p-CS and p-CG, is similar in mouse, in contrast to humans, pinpointing major inter-species differences in endogenous metabolism. Biologically, the sulpho- (i.e. p-CS) but not the glucuro- (i.e. p-CG) conjugate promotes insulin resistance in CKD.

ACS Style

Laetitia Koppe; Pascaline M Alix; Marine L Croze; Stéphane Chambert; Raymond Vanholder; Griet Glorieux; Denis Fouque; Christophe O Soulage. 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. Nephrology Dialysis Transplantation 2017, 32, 2000 -2009.

AMA Style

Laetitia Koppe, Pascaline M Alix, Marine L Croze, Stéphane Chambert, Raymond Vanholder, Griet Glorieux, Denis Fouque, Christophe O Soulage. 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. Nephrology Dialysis Transplantation. 2017; 32 (12):2000-2009.

Chicago/Turabian Style

Laetitia Koppe; Pascaline M Alix; Marine L Croze; Stéphane Chambert; Raymond Vanholder; Griet Glorieux; Denis Fouque; Christophe O Soulage. 2017. "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." Nephrology Dialysis Transplantation 32, no. 12: 2000-2009.

Journal article
Published: 01 May 2017 in Nephrology Dialysis Transplantation
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INTRODUCTION AND AIMS: Most chronic kidney disease (CKD) patients suffer from 25OH vitamin D deficiency , which might contribute to adverse health outcomes. It has been proposed that serum free 25OHvitD better reflects vitamin D metabolism. We aim to evaluate whether serum free 25OHvitD varies regarding the different stages of CKD, in comparison with total 25OHvitD.

ACS Style

Anaïs Bouchara; Marie-Christine Carlier; Laetitia Koppe; Mathilde Nouvier; Maurice Laville; Bertille Pommier; Denis Fouque; Solenne Pelletier. SP351INTEREST OF FREE VITAMIN D IN CKD. Nephrology Dialysis Transplantation 2017, 32, iii228 -iii228.

AMA Style

Anaïs Bouchara, Marie-Christine Carlier, Laetitia Koppe, Mathilde Nouvier, Maurice Laville, Bertille Pommier, Denis Fouque, Solenne Pelletier. SP351INTEREST OF FREE VITAMIN D IN CKD. Nephrology Dialysis Transplantation. 2017; 32 (suppl_3):iii228-iii228.

Chicago/Turabian Style

Anaïs Bouchara; Marie-Christine Carlier; Laetitia Koppe; Mathilde Nouvier; Maurice Laville; Bertille Pommier; Denis Fouque; Solenne Pelletier. 2017. "SP351INTEREST OF FREE VITAMIN D IN CKD." Nephrology Dialysis Transplantation 32, no. suppl_3: iii228-iii228.