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Article ; Online: Chronic Kidney Disease-Associated Immune Dysfunctions

Maxime Espi / Laetitia Koppe / Denis Fouque / Olivier Thaunat

Toxins, Vol 12, Iss 300, p

Impact of Protein-Bound Uremic Retention Solutes on Immune Cells

2020 Volume 300

Abstract: 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 ... ...

Abstract	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.
Keywords	chronic kidney disease ; uremic toxins ; immune system ; Medicine ; R
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Role of Gut Microbiota and Diet on Uremic Retention Solutes Production in the Context of Chronic Kidney Disease

Laetitia Koppe / Denis Fouque / Christophe O. Soulage

Toxins, Vol 10, Iss 4, p

2018 Volume 155

Abstract: 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 ... ...

Abstract	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.
Keywords	chronic kidney disease ; intestinal microbiota ; pro/prebiotics ; vegetarian diet ; low protein diet ; nutrient composition ; uremic toxins ; Medicine ; R
Language	English
Publishing date	2018-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD

Christophe Barba / Christophe O. Soulage / Gianvito Caggiano / Griet Glorieux / Denis Fouque / Laetitia Koppe

Toxins, Vol 12, Iss 741, p

2020 Volume 741

Abstract: 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 ... ...

Abstract	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.
Keywords	chronic kidney disease ; fecal microbiota transplantation ; uremic toxins ; p-cresyl-sulfate ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice

Berengère Benoit / Alice Beau / Émilie Bres / Stéphanie Chanon / Claudie Pinteur / Aurélie Vieille-Marchiset / Audrey Jalabert / Hao Zhang / Priyanka Garg / Maura Strigini / Laurence Vico / Jérôme Ruzzin / Hubert Vidal / Laetitia Koppe

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 13

Abstract: Abstract Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We ... ...

Abstract	Abstract Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: First viral replication of Covid-19 identified in the peritoneal dialysis fluid of a symptomatic patient

Mathilde Nouvier / Elodie Chalençon / Etienne Novel-Catin / Solenne Pelletier / Patrick Hallonet / Caroline Charre / Laetitia Koppe / Denis Fouque

Bulletin de la Dialyse à Domicile, Vol 3, Iss

2020 Volume 1

Abstract: The COVID-19 pandemic is characterized by a disease with mainly respiratory tropism and varying severity. Viral excretion of COVID-19 has been described in both urine and stool with the risk of contamination by stool. No viral replication in the ... ...

Abstract	The COVID-19 pandemic is characterized by a disease with mainly respiratory tropism and varying severity. Viral excretion of COVID-19 has been described in both urine and stool with the risk of contamination by stool. No viral replication in the peritoneal dialysis fluid has been reported to date. We report an observation demonstrating the presence of the virus in the peritoneal dialysis drainage fluid of a COVID-19 patient. This underlines the importance in COVID-19 patients of considering dialysis fluid as a possible source of contamination.
Keywords	SARS-CoV2 ; COVID-19 ; peritoneal dialysis ; dialysate ; Internal medicine ; RC31-1245 ; covid19
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	RDPLF
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distal Colon Motor Dysfunction in Mice with Chronic Kidney Disease

Elsa Hoibian / Nans Florens / Laetitia Koppe / Hubert Vidal / Christophe O. Soulage

Toxins, Vol 10, Iss 5, p

Putative Role of Uremic Toxins

2018 Volume 204

Abstract: 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 ... ...

Abstract	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.
Keywords	uremia ; chronic kidney disease ; gastrointestinal motility ; colon ; uremic toxins ; Medicine ; R
Subject code	616
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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

Christophe Barba / Bérengère Benoit / Emilie Bres / Stéphanie Chanon / Aurélie Vieille-Marchiset / Claudie Pinteur / Sandra Pesenti / Griet Glorieux / Cécile Picard / Denis Fouque / Christophe O. Soulage / Laetitia Koppe

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract 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) ...

Abstract	Abstract 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.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prebiotics improve metabolic parameter in uremic mice by reducing intestinal production of p-cresyl sulfate

Laetitia Koppe / Caroline Pelletier / Denis Fouque / Christophe Soulage

Kidney Research and Clinical Practice, Vol 31, Iss 2, p A

2012 Volume 48

Abstract: Chronic kidney disease (CKD) is associated with a large range of metabolic alterations. P-cresyl sulfate (PCS) has been identified as one of the main uremic toxins involved in the pathogenesis of accelerated atherosclerosis in CKD. The prebiotic soluble ... ...

Abstract	Chronic kidney disease (CKD) is associated with a large range of metabolic alterations. P-cresyl sulfate (PCS) has been identified as one of the main uremic toxins involved in the pathogenesis of accelerated atherosclerosis in CKD. The prebiotic soluble fibers have the property of selectively stimulate growth and activity of a limited number of beneficial bacteria in the colon. The aim of this study is to assess in mice the effects of prebiotics by the reduction of PCS intestinal production, on metabolic disturbances associated with CKD. Subtotally nephrectomized C57BL/6J wild-type mice were divided into two groups: CKD mice and CKD mice fed with 5% (w/w standard diet) of prebiotic arabinoxylane oligosaccharides (AXOS, WITAXOS SA,). Three weeks after initiation of prebiotics serum cholesterol total, triglycerides, glucose, PCS were measured. The insulin sensitivity was estimated by intra-peritoneal insulin tolerance test and glucose tolerance test. CKD mice treated with AXOS exhibited a significant decrease in serum total PCS (−74%, p=0.03). Prebiotic treatment reduced the loss of fat mass observed in CKD (+33%, p<0.05). and prevented the ectopic lipid redistribution associated with CKD. Prebiotic treatment completely prevented the expected increase in glycemia, total cholesterol and triglycerides associated with CKD. Insulin sensitivity was significantly improved in prebiotic group. These results suggest that prebiotics AXOS decrease PCS and prevented CKD-induced insulin resistance, the loss of adipose tissue and prevented accumulation of ectopic lipids in muscle and liver. Because insulin resistance is an important cardiovascular risk factor, novel therapeutic approaches like prebiotics which could decrease PCS and cardio vascular mortality.
Keywords	Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951
Subject code	630
Language	English
Publishing date	2012-06-01T00:00:00Z
Publisher	The Korean Society of Nephrology
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of lipotoxicity in insulin resistance in subtotally nephrectomized mouse model

Laetitia Koppe / Caroline Pelletier / Roxane Vella / Denis Fouque / Fitsum Guebre-Egziahber / Christophe Soulage

Kidney Research and Clinical Practice, Vol 31, Iss 2, p A

2012 Volume 49

Abstract: Chronic kidney disease (CKD) is associated with a large range of metabolic alterations among which insulin resistance and dyslipidemia. We hypothesize that a phenomenon of lipotoxicity and ectopic fat redistribution could be responsible for the insulin- ... ...

Abstract	Chronic kidney disease (CKD) is associated with a large range of metabolic alterations among which insulin resistance and dyslipidemia. We hypothesize that a phenomenon of lipotoxicity and ectopic fat redistribution could be responsible for the insulin-resistance associated to CKD. C57BL/6 mice underwent a 5/6 nephrectomy and were compared to pair fed sham-operated mice. Insulin sensitivity was estimated through intra-peritoneal insulin (ipITT) and glucose tolerance (ipGTT) tests. Anthropometric (body weight, lean and fad pad mass) and metabolic parameters (glycemia, insulin, cholesterol, triglycerides) were measured. The phosphorylation of a key protein of insulin signaling pathway (protein kinase B, PKB/Akt) was studied by Western blot. The intra-muscular and intra-hepatic lipids were extracted using Chloroform-Methanol (2:1, v/v). The CKD mice exhibited a marked decrease in insulin sensitivity (−76%, p<0.01) and altered glucose tolerance (+24%, p<0.001). CKD mice exhibited a profile of insulin resistance. CKD mice exhibited a significant decrease in white adipose tissue accretion (−57%, p< 0.001) associated with increased muscle (+138%, p<0.05) and liver (+38%, P<0.05) lipid contents compared to sham-operated mice. The CKD mice presented a blunted insulin-induced Akt phosphorylation (−34%, p<0.05) in gastrocnemius muscle. In subtotally nephrectomized mouse model we showed an ectopic intramuscular and intrahepatic lipid redistribution concomitant with insulin resistance. Insulin resistance and lipotoxicity may represent the missing links (beyond the classical cardiovascular risk factors) that may help explain the increased risk of cardiovascular disease in CKD.
Keywords	Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951
Subject code	616
Language	English
Publishing date	2012-06-01T00:00:00Z
Publisher	The Korean Society of Nephrology
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The relationship between renal function and plasma concentration of the cachectic factor zinc-alpha2-glycoprotein (ZAG) in adult patients with chronic kidney disease.

Caroline C Pelletier / Laetitia Koppe / Pascaline M Alix / Emilie Kalbacher / Marine L Croze / Aoumeur Hadj-Aissa / Denis Fouque / Fitsum Guebre-Egziabher / Christophe O Soulage

PLoS ONE, Vol 9, Iss 7, p e

2014 Volume 103475

Abstract: Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the ... ...

Abstract	Zinc-α2-glycoprotein (ZAG), a potent cachectic factor, is increased in patients undergoing maintenance dialysis. However, there is no data for patients before initiation of renal replacement therapy. The purpose of the present study was to assess the relationship between plasma ZAG concentration and renal function in patients with a large range of glomerular filtration rate (GFR). Plasma ZAG concentration and its relationship to GFR were investigated in 71 patients with a chronic kidney disease (CKD) stage 1 to 5, 17 chronic hemodialysis (HD), 8 peritoneal dialysis (PD) and 18 non-CKD patients. Plasma ZAG concentration was 2.3-fold higher in CKD stage 5 patients and 3-fold higher in HD and PD patients compared to non-CKD controls (P<0.01). The hemodialysis session further increased plasma ZAG concentration (+39%, P<0.01). An inverse relationship was found between ZAG levels and plasma protein (rs = -0.284; P<0.01), albumin (rs = -0.282, P<0.05), hemoglobin (rs = -0.267, P<0.05) and HDL-cholesterol (rs = -0.264, P<0.05) and a positive correlation were seen with plasma urea (rs = 0.283; P<0.01). In multiple regression analyses, plasma urea and HDL-cholesterol were the only variables associated with plasma ZAG (r2 = 0.406, P<0.001). In CKD-5 patients, plasma accumulation of ZAG was not correlated with protein energy wasting. Further prospective studies are however needed to better elucidate the potential role of ZAG in end-stage renal disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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