📇 Rhumatologue · PARIS CEDEX 20 · (75) · Hospitalier

M EMMANUEL LETAVERNIER

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5 raisons identifiées

Plateau technique de référence
Assistance publique – Hôpitaux de Paris (APHP) — équipements et expertise pointus pour les cas complexes
Auteur de référence en rhumatologie
20 articles scientifiques publiés — un praticien à la pointe de la recherche
Encadrant universitaire
Forme la prochaine génération de rhumatologues (6 thèses dirigées)
Expérience confirmée
18 ans d'exercice en rhumatologie — recul clinique solide
Délais de RDV courts dans la région
336.2 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 PARIS CEDEX 20 (75)HospitalierRPPS 10001604916

EnseignementExpérience confirmée

18ans d'exercice (thèse 2008)

📊 Reconnaissance scientifique : 45/100📝 294 articles publiés🇫🇷 Publications académiques françaises (8)🎓 6 thèses dirigées

Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

Podocyte Injury in Diabetic Kidney Disease in Mouse Models Involves TRPC6-mediated Calpain Activation Impairing Autophagy

Journal of the American Society of Nephrology : JASN · 2023

📚 56 citations🎯 RCR 7.16Top 4% NIH🔓 Open Access

Lire l'abstract Crossref ↓

Significance Statement Autophagy protects podocytes from injury in diabetic kidney disease (DKD). Restoring glomerular autophagy is a promising approach to limit DKD. This study demonstrates a novel regulatory mechanism of autophagy that blocks this critical protection of the glomerular filtration barrier. We demonstrated that TRPC6 induced in podocytes in mouse models of diabetes mediates calpain activation, thereby impairing podocyte autophagy, causing injury and accelerating DKD. Furthermore, this study provides proof of principle for druggable targets for DKD because restoration of podocyte autophagy by calpain inhibitors effectively limits glomerular destruction. Background Diabetic kidney disease is associated with impaired podocyte autophagy and subsequent podocyte injury. The regulation of podocyte autophagy is unique because it minimally uses the mTOR and AMPK pathways. Thus, the molecular mechanisms underlying the impaired autophagy in podocytes in diabetic kidney disease remain largely elusive. Methods This study investigated how the calcium channel TRPC6 and the cysteine protease calpains deleteriously affect podocyte autophagy in diabetic kidney disease in mice. We demonstrated that TRPC6 knockdown in podocytes increased the autophagic flux because of decreased cysteine protease calpain activity. Diabetic kidney disease was induced in vivo using streptozotocin with unilateral nephrectomy and the BTBRob/ob mouse models. Results Diabetes increased TRPC6 expression in podocytes in vivo with decreased podocyte autophagic flux. Transgenic overexpression of the endogenous calpain inhibitor calpastatin, as well as pharmacologic inhibition of calpain activity, normalized podocyte autophagic flux, reduced nephrin loss, and prevented the development of albuminuria in diabetic mice. In kidney biopsies from patients with diabetes, we further confirmed that TRPC6 overexpression in podocytes correlates with decreased calpastatin expression, autophagy blockade, and podocyte injury. Conclusions Overall, we discovered a new mechanism that connects TRPC6 and calpain activity to impaired podocyte autophagy, increased podocyte injury, and development of proteinuria in the context of diabetic kidney disease. Therefore, targeting TRPC6 and/or calpain to restore podocyte autophagy might be a promising therapeutic strategy for diabetic kidney disease.

Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms

Journal of the American Society of Nephrology : JASN · 2022

📚 39 citations🎯 RCR 3.56Top 13% NIH🔓 Open Access📄 PDF gratuit ↗

Lire l'abstract Crossref ↓

Significance Statement The pathophysiology of AKI during tumor lysis syndrome (TLS) is not fully understood. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI. Analyzing urine and blood from patients with TLS provided data on crystal-independent mechanisms of the pathogenesis of AKI during TLS. We also explored mechanisms of TLS-induced AKI in vitro and in vivo in a murine model of TLS (syngeneic mice with acute myeloid leukemia receiving chemotherapy). We found that extracellular histones released in huge amounts during TLS profoundly alter the endothelium. Nonanticoagulant heparin mitigated AKI in this model. Background The pathophysiology of AKI during tumor lysis syndrome (TLS) is not well understood due to the paucity of data. We aimed to decipher crystal-dependent and crystal-independent mechanisms of TLS-induced AKI. Methods Crystalluria, plasma cytokine levels, and extracellular histones levels were measured in two cohorts of patients with TLS. We developed a model of TLS in syngeneic mice with acute myeloid leukemia, and analyzed ultrastructural changes in kidneys and endothelial permeability using intravital confocal microscopy. In parallel, we studied the endothelial toxicity of extracellular histones in vitro. Results The study provides the first evidence that previously described crystal-dependent mechanisms are insufficient to explain TLS-induced AKI. Extracellular histones that are released in huge amounts during TLS caused profound endothelial alterations in the mouse model. The mechanisms of histone-mediated damage implicates endothelial cell activation mediated by Toll-like receptor 4. Heparin inhibits extracellular histones and mitigates endothelial dysfunction during TLS. Conclusion This study sheds new light on the pathophysiology of TLS-induced AKI and suggests that extracellular histones may constitute a novel target for therapeutic intervention in TLS when endothelial dysfunction occurs.

Exome-First Strategy in Adult Patients With CKD: A Cohort Study

Kidney international reports · 2023

📚 20 citations🎯 RCR 1.84🔓 Open Access

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M EMMANUEL LETAVERNIER

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Thèses universitaires

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Publications académiques en France

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Top publications · les plus citées

Publications scientifiques (20) — classées par pathologie

Transversal12

Case report / série2

Goutte2

Revue générale2

Épidémiologie & registres1

Pédiatrie1

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