Publications (27) View all
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Article: Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway.
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ABSTRACT: In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a 'dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients.Kidney International advance online publication, 1 May 2013; doi:10.1038/ki.2013.133.Kidney International 05/2013; · 6.61 Impact Factor -
Article: Acute Renal Infarction: A Case Series.
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ABSTRACT: BACKGROUND AND OBJECTIVES: Renal infarction is an arterial vascular event that may cause irreversible damage to kidney tissues. This study describes the clinical characteristics of patients with renal infarction according to underlying mechanism of vascular injury. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study retrospectively identified 94 patients with renal infarction diagnosed between 1989 and 2011 with the aim of highlighting potential correlations between demographic, clinical, and biologic characteristics and the etiology of renal infarction. Four groups were identified: renal infarction of cardiac origin (cardiac group, n=23), renal infarction associated with renal artery injury (renal injury group, n=29), renal infarction associated with hypercoagulability disorders (hypercoagulable group, n=15), and apparently idiopathic renal infarction (idiopathic group, n=27). RESULTS: Clinical symptoms included abdominal and/or flank pain in 96.8% of cases; 46 patients had uncontrolled hypertension at diagnosis. Laboratory findings included increase of lactate dehydrogenase level (90.5%), increase in C-reactive protein level (77.6%), and renal impairment (40.4%). Compared with renal injury group patients, this study found that cardiac group patients were older (relative risk for 1 year increase=1.21, P=0.001) and displayed a lower diastolic BP (relative risk per 1 mmHg=0.94, P=0.05). Patients in the hypercoagulable group had a significantly lower diastolic BP (relative risk=0.86, P=0.005). Patients in the idiopathic group were older (relative risk=1.13, P=0.01) and less frequently men (relative risk=0.11, P=0.02). Seven patients required hemodialysis at the first evaluation, and zero patients died during the first 30 days. CONCLUSIONS: This study suggests that the clinical and biologic characteristics of patients can provide valuable information about the causal mechanism involved in renal infarction occurrence.Clinical Journal of the American Society of Nephrology 11/2012; · 5.23 Impact Factor -
Article: [Kidney involvement in hematologic malignancies. Diagnostic approach].
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ABSTRACT: Kidney involvement is frequent in hematologic malignancies. It is associated with adverse outcome and treatment difficulties. It can affect every area of the renal parenchyma (tubules, interstitium, glomerulus, vessels). Various mechanisms could be implicated: deposits of immunoglobulin fractions or crystals, renal infiltration by malignant cells, urinary tract obstruction, paraneoplastic or storage glomerulopathies… Diagnostic strategy relies on the clinical presentation: acute renal failure, chronic kidney disease, glomerular proteinuria with or without nephrotic syndrome, tubular proteinuria, hydroelectrolytic disorders. In this review, we detail the diagnostic tests that are needed for the detection and the follow-up of renal involvement in hematologic malignancies, and clarify the indications of renal biopsy. We propose diagnostic strategies of renal involvement in myeloma, Waldenström's disease, high grade lymphomas and acute leukemias, low grade lymphomas and chronic leukemias. The adverse effects of treatments (chemotherapy, radiotherapy, stem cell graft …) are not addressed in this review.La Revue de Médecine Interne 10/2010; 31(10):685-96. · 0.61 Impact Factor -
Article: PROGRESS IN UREMIC TOXIN RESEARCH: Protein‐Bound Toxins—Update 2009
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ABSTRACT: Protein-bound uremic retention solutes constitute a group whose common characteristic is their difficult removal by dialysis. In 2003, the EUTox group described 25 protein-bound solutes. They comprised six advanced glycation end products (AGE), four phenols (including p-cresol), six indoles (including indoxylsulfate), two hippurates, three polyamines, and two peptides, homocysteine and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). As then, three new compounds have been added to the list: phenylacetic acid, dinucleoside polyphosphates, and IL-18. During the last years, protein-bound compounds have been identified as some of the main toxins involved in vascular lesions of chronic kidney disease. The removal of these solutes by conventional hemodialysis (HD) is low because only the free fraction of the solute is available for diffusion. The increase in the convective part with hemodiafiltration improves the performance of depuration but convection only applies to the free fraction and its benefit is limited. One possibility to improve the removal of a protein-bound solute would be to stimulate its dissociation from the binding protein. This could be obtained in experiments by setting the dialysate flow rate and the dialyzer mass transfer area coefficient (KoA) at much higher levels than the plasma flow rate, or by adding to the dialysate a sorbent such as activated charcoal or albumin. In the future, specific adsorbents may be developed. Today, the only possibility is to use approaches such as daily HD and long HD which could allow better equilibration between extravascular and vascular compartments and consequently result in greater removal of protein-bound compounds.Seminars in Dialysis 08/2009; 22(4):334 - 339. · 2.27 Impact Factor -
Article: A&R special issue: Disease mechanisms in rheumatology: Tools and pathways.
Arthritis & Rheumatism 02/2013; · 7.87 Impact Factor
