Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients

International audienceBackground: The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS)-three protein bound uremic toxins-are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients. Methods: Between June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses

Vancomycin-induced Henoch-Schönlein purpura: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura.</p> <p>Case presentation</p> <p>A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature.</p> <p>Conclusions</p> <p>Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.</p

Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. <it>Legionella pneumophila </it>serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically.</p> <p>Conclusions</p> <p>This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.</p

High Resolution Melt analysis for mutation screening in PKD1 and PKD2

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. <it>PKD1 </it>and <it>PKD2 </it>have been implicated in ADPKD pathogenesis but genetic features and the size of <it>PKD1 </it>make genetic diagnosis tedious.</p> <p>Methods</p> <p>We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in <it>PKD1 </it>and <it>PKD2 </it>with HRM in 37 unrelated patients with ADPKD.</p> <p>Results</p> <p>We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in <it>PKD1 </it>and 3 in <it>PKD2 </it>) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in <it>PKD1 </it>and two in <it>PKD2</it>.</p> <p>Conclusion</p> <p>HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.</p

Impact of chronic kidney disease on myostatin accumulation and muscle regeneration : role of indoxyl sulfate

La myostatine est une protéine dont le rôle est de freiner la croissance musculaire. Les concentrations sanguines de myostatine augmentent au cours de l’insuffisance rénale chronique (IRC). Certains auteurs font l’hypothèse d’une augmentation de sa production par les muscles sous l’effet de l’indoxyl sulfate (IS), une toxine urémique dérivée du tryptophane. Dans cette thèse nous montrons grâce à des modèles murins d’IRC et dans un modèle cellulaire qu’il n’y a pas de surproduction de myostatine par les cellules musculaires sous l’effet de l’IRC ou de l’IS. La myostatine s’accumule au cours de la MRC du fait d’une diminution de son élimination rénale plutôt que du fait d’une augmentation de production.Nous analysons ensuite l’effet de l’IS sur la régénération musculaire grâce à un modèle de lignée cellulaire de myoblastes (cellules souches permettant la régénération musculaire) murins, les C2C12. Nous montrons que l’exposition des C2C12 à l’IS durant leur différenciation en myotubes conduit à des myotubes plus fins et contenant moins de noyaux que les contrôles, suggérant que l’IS inhibe la régénération musculaire. En analysant les gènes impliqués dans la différenciation des myoblastes en myotubes, nous mettons en évidence que l’IS inhibe l’expression du gène Myf6 qui code pour un facteur de différenciation appelé Mrf4. Mrf4 est un facteur de transcription impliqué dans la phase tardive de la différenciation (fusion myocytes-myocyte ou fusion myocyte-myotube) ainsi que dans l’innervation des fibres musculaires. Ainsi, l’IRC conduit à la sarcopénie par une diminution de la capacité de régénération musculaire induite par l’IS via l’inhibition de l’expression de Myf6.Myostatin is a protein secreted by mature muscle cells that inhibits striated muscle growth. Recent publications suggest that myostatin accumulates during chronic kidney disease (CKD). Some hypothesize that it is overproduced by muscle cells during CKD under the effect of indoxyl sulfate, an indolic uremic solute. In the first part of this thesis, using mice models and cellular culture of myocytes, we demonstrate that there is no overproduction of myostatin in muscle cells during CKD or after exposure to indoxyl sulfate, suggesting that myostatin accumulates because of a lack of renal clearance rather than overproduction during CKD.In the second part of the thesis, we analyze the impact of indoxyl sulfate on muscle regeneration. We used an in vitro cellular culture model of murine myoblasts (pluripotent cells which proliferate and differentiate in mature muscle cells) called C2C12. We demonstrate that when C2C12 cells are exposed to indoxyl sulfate during differentiation, final myotubes are thinner and exert less nucleus per myotube, suggesting that indoxyl sulfate inhibits muscle cell differentiation. We then analyzed the genes expression of the Muscle Regulating Factors which are transcription factors that organize and regulate differentiation. We report on that indoxyl sulfate inhibits the transcription of the Myf6 gene. Mrf4 (the protein coded by the Myf6 gene) is a transcription factor regulating the late phase of transcription (myocyte-myocyte fusion and myocyte-myotube fusion) as well as the innervation of muscle fibers. Thus, CKD could lead to sarcopenia via impaired muscle regeneration due to Myf6 transcription inhibition by indoxyl sulfate

Mise au point du dépistage des mutations dans PKD1 et PKD2 par High Resolution Melt

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Annonce de la création de l’Association francophone de diététique et nutrition dans les maladies rénales

International audienc

Dysfonction du cathéter de dialyse péritonéale due à des caillots de fibrine suite à un traitement par acide tranexamique : un cas clinique.

Chronic kidney disease patients experience not only more frequent arterial and venous thrombosis but also hemorrhagic episodes. Tranexamic acid is an anti-fibrinolytic molecule that inhibits plasmin activation. It is used in hemorrhage cases (post-traumatic, gynecologic, or gastrointestinal bleeding). We report on an original case of tranexamic acid (Exacyl®) use in a peritoneal dialysis patient for gastrointestinal bleeding of unknown origin. The use of tranexamic acid led to the Tenckhoff catheter dysfunction because of fibrin clots in the dialysate. The emergence of fibrin clots a few days after the start of tranexamic acid treatment, which never occurred again after the end of the treatment, and the anti-fibrinolytic function of tranexamic acid favors this treatment’s role in fibrin clot occurrence.Les patients insuffisants rénaux chroniques (IRC) présentent un risque plus élevé de thrombose artérielle et veineuse, mais également de complications hémorragiques. L’acide tranexamique est une molécule anti-fibrinolytique qui inhibe le clivage de plasminogène en plasmine et est utilisé dans les syndromes hémorragiques (polytraumatisé, hémorragies gynécologiques ou digestives). Nous rapportons un cas original d’utilisation de l’acide tranexamique (Exacyl®) chez une patiente en dialyse péritonéale qui présentait une hémorragie digestive inexpliquée. Le traitement par acide tranexamique a été compliqué par une dysfonction du cathéter de Tenckhoff en raison de son obstruction par des caillots de fibrine dans le dialysat. La cinétique de survenue des caillots de fibrine juste après la mise en route du traitement chez une patiente n’ayant jamais présenté ce type de complications ni avant le traitement, ni après son arrêt ainsi que son pouvoir anti fibrinolytique sont en faveur d’une implication de ce traitement

Moderate-to-severe pruritus in untreated or non-responsive hemodialysis patients: results of the French prospective multicenter observational study Pruripreva

International audienceABSTRACT Background Chronic kidney disease-associated pruritus (CKD-aP) is a common condition in patients treated with hemodialysis, and has a negative impact on quality of life (QoL). Due to the lack of standardized diagnostic tools and frequent underreporting, pruritus prevalence remains poorly documented. Methods Pruripreva was a prospective multicenter observational study that aimed to evaluate the prevalence of moderate to severe pruritus in a cohort of French hemodialysis patients. The primary endpoint was the rate of patients with mean Worst Itch Numerical Rating Scale (WI-NRS) score ≥4 calculated over 7 days (moderate pruritus, 4–6; severe, 7–8; very severe, 9–10). Impact of CKD-aP on QoL was analyzed according to its severity (WI-NRS), using 5-D Itch scale, EQ-5D and Short Form (SF)-12. Results Mean WI-NRS was ≥4 in 306 patients (mean age, 66.6 years; male, 57.6%) out of 1304 and prevalence of moderate to very severe pruritus was 23.5% (95% confidence interval 21.2–25.9). Pruritus was unknown prior to the systematic screening in 37.6% of patients, and 56.4% of those affected were treated for this condition. The more severe the pruritus, the poorer the QoL according to the 5-D Itch scale, EQ-5D and SF-12. Conclusion Moderate to very severe pruritus was reported in 23.5% of hemodialysis patients. CKD-aP was underrated although it is associated with a negative impact on QoL. These data confirm that pruritus in this setting is an underdiagnosed and underreported condition. There is an urgent demand for new therapies to treat chronic pruritus associated with CKD in hemodialysis patients

Source and Composition in Amino Acid of Dietary Proteins in the Primary Prevention and Treatment of CKD

International audienceNutrition 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