Author: "Emmanuel Letavernier" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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1. Sulfamethoxazole-induced crystal nephropathy: characterization and prognosis in a case series

Author: Ruben Azencot, Camille Saint-Jacques, Jean-Philippe Haymann, Vincent Frochot, Michel Daudon, and Emmanuel Letavernier
Subjects: Sulfamethoxazole, Crystal, Crystalluria, Acute kidney injury, Medicine, Science
Abstract: Abstract Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.
Published: 2024
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2. Abcc6 deficiency prevents rhabdomyolysis-induced acute kidney injury

Author: Audrey Casemayou, Julie Belliere, Emmanuel Letavernier, Eloïse Colliou, Hélène El Hachem, Jeremy Zarowski, Dominique Bazin, Clément Kounde, Alexis Piedrafita, Guylène Feuillet, Joost P. Schanstra, and Stanislas Faguer
Subjects: Medicine, Science
Abstract: Abstract Rhabdomyolysis is a risk factor for acute kidney injury, transition towards chronic kidney disease, and death. The role of calcium phosphate deposits in the mechanisms of rhabdomyolysis-induced acute kidney injury (RAKI) is still unclear. Better insight of the role calcium in RAKI could lead to new therapeutic avenues. Here, we show in a mice model of RAKI that calcium phosphate deposits were frequent in the kidney (hydroxyapatite) and partly correlated with the severity of the kidney injury. However, the intensity of deposits was highly heterogeneous between mice. Treatment with sodium chloride, sodium bicarbonate or inorganic pyrophosphate (PPi; an inhibitor of the calcium phosphate crystallization), or combinations thereof, did not improve kidney outcomes and hydroxyapatite deposition during RAKI. Unexpectedly, Abcc6 knockout mice (ko), characterized by PPi deficiency, developed less severe RAKI despite similar rhabdomyolysis severity, and had similar hydroxyapatite deposition suggesting alternative mechanisms. This improved kidney outcome at day 2 translated to a trend in improved glomerular filtration rate at month 2 in Abcc6 -/- mice and to significantly less interstitial fibrosis. In addition, whereas the pattern of infiltrating cells at day 2 was similar between wt and ko mice, kidneys of Abcc6 -/- mice were characterized by more CD19+ B-cells, less CD3+ T-cells and a lower R1/R2 macrophage ratio at month 2. In summary, kidney calcium phosphate deposits are frequent in RAKI but hydration with sodium bicarbonate or sodium chloride does not modify the kidney outcome. Blocking ABCC6 emerges as a new option to prevent RAKI and subsequent transition toward kidney fibrosis.
Published: 2023
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3. Elastic fiber alterations and calcifications in calcific uremic arteriolopathy

Author: Hester Colboc, Philippe Moguelet, Dominique Bazin, Emmanuel Letavernier, Chenyu Sun, Anatole Chessel, Priscille Carvalho, Catherine Lok, Anne-Sophie Dillies, Guillaume Chaby, Hervé Maillard, Diane Kottler, Elisa Goujon, Christine Jurus, Marine Panaye, Ellie Tang, Philippe Courville, Antoine Boury, Jean-Benoit Monfort, François Chasset, Patricia Senet, and Marie-Claire Schanne-Klein
Subjects: Medicine, Science
Abstract: Abstract Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber’s alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.
Published: 2023
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4. Relationship between clinical phenotype and in vitro analysis of 13 NPT2c/SCL34A3 mutants

Author: François Brazier, Marie Courbebaisse, Amandine David, David Bergerat, Christine Leroy, Marta Lindner, Gérard Maruani, Camille Saint Jacques, Emmanuel Letavernier, Marguerite Hureaux, Rosa Vargas-Poussou, and Dominique Prié
Subjects: Medicine, Science
Abstract: Abstract Biallelic pathogenic variants in the SLC34A3 gene, encoding for the NPT2c cotransporter, cause Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH). However, the associated phenotype is highly variable. In addition, mice deleted for Slc34a3 exhibit a different phenotype compared to humans, without urinary phosphate leakage. The mechanisms by which SLC34A3 variants disrupt phosphate/calcium metabolism are un-completely understood. In this study we explored these mechanisms in vitro using SLC34A3 variants identified in patients with urinary phosphate leakage. We analyzed the consequences of these variants on NPT2c function and the link with the phenotype of the patients. We studied 20 patients with recurrent nephrolithiasis and low serum phosphate concentration harboring variants in the SLC34A3 gene. Half of the patients carried homozygous or composite heterozygous variants. Three patients had in addition variants in SLC34A1 and SLC9A3R1 genes. All these patients benefited from a precise analysis of their phenotype. We generated 13 of these mutants by site-directed mutagenesis. Then we carried out transient transfections of these mutants in HEK cells and measured their phosphate uptake capacity under different conditions. Among the 20 patients included, 3 had not only mutations in NPT2c but also in NPT2a or NHERF1 genes. Phosphate uptake was decreased in 8 NPT2c mutants studied and normal for 5. Four variants were initially categorized as variants of uncertain significance. Expression of the corresponding mutants showed that one did not modify phosphate transport, two reduced it moderately and one abolished it. Co-transfection of the NPT2c mutants with the wild-type plasmid of NPT2c or NPT2a did not reveal dominant negative effect of the mutants on NPT2c-mediated phosphate transport. A detailed analysis of patient phenotypes did not find a link between the severity of the disorder and the level of phosphate transport impairment. NPT2c mutations classified as ACMG3 identified in patients with renal phosphate leak should be characterized by in vitro study to check if they alter NPT2c-mediated phosphate transport since phosphate uptake capacity may not be affected. In addition, research for mutations in NHERF1 and NPT2a genes should always be associated to NPT2c sequencing.
Published: 2023
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5. Towards routine 3D characterization of intact mesoscale samples by multi-scale and multimodal scanning X-ray tomography

Author: Ruiqiao Guo, Andrea Somogyi, Dominique Bazin, Elise Bouderlique, Emmanuel Letavernier, Catherine Curie, Marie-Pierre Isaure, and Kadda Medjoubi
Subjects: Medicine, Science
Abstract: Abstract Non-invasive multi-scale and multimodal 3D characterization of heterogeneous or hierarchically structured intact mesoscale samples is of paramount importance in tackling challenging scientific problems. Scanning hard X-ray tomography techniques providing simultaneous complementary 3D information are ideally suited to such studies. However, the implementation of a robust on-site workflow remains the bottleneck for the widespread application of these powerful multimodal tomography methods. In this paper, we describe the development and implementation of such a robust, holistic workflow, including semi-automatic data reconstruction. Due to its flexibility, our approach is especially well suited for on-the-fly tuning of the experiments to study features of interest progressively at different length scales. To demonstrate the performance of the method, we studied, across multiple length scales, the elemental abundances and morphology of two complex biological systems, Arabidopsis plant seeds and mouse renal papilla samples. The proposed approach opens the way towards routine multimodal 3D characterization of intact samples by providing relevant information from pertinent sample regions in a wide range of scientific fields such as biology, geology, and material sciences.
Published: 2022
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6. Combining robust urine biomarkers to assess chronic kidney disease progressionResearch in context

Author: Frank Bienaimé, Mordi Muorah, Marie Metzger, Melanie Broeuilh, Pascal Houiller, Martin Flamant, Jean-Philippe Haymann, Jacky Vonderscher, Jacques Mizrahi, Gérard Friedlander, Bénédicte Stengel, Fabiola Terzi, François Vrtovsnik, Eric Daugas, Emmanuelle Vidal-Petiot, Christian Jacquot, Alexandre Karras, Stéphane Roueff, Eric Thervet, Pascal Houillier, Marie Courbebaisse, Dominique Eladari et Gérard Maruani, Pablo Urena-Torres, Jean-Jacques Boffa, Pierre Ronco, H. Fessi, Eric Rondeau, Emmanuel Letavernier, and Nahid Tabibzadeh
Subjects: Chronic kidney disease progression, Urinary biomarkers, EGF, TGF-α, CCL2, NGAL, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Urinary biomarkers may improve the prediction of chronic kidney disease (CKD) progression. Yet, data reporting the applicability of most commercial biomarker assays to the detection of their target analyte in urine together with an evaluation of their predictive performance are scarce. Methods: 30 commercial assays (ELISA) were tested for their ability to quantify the target analyte in urine using strict (FDA-approved) validation criteria. In an exploratory analysis, LASSO (Least Absolute Shrinkage and Selection Operator) logistic regression analysis was used to identify potentially complementary biomarkers predicting fast CKD progression, determined as the 51CrEDTA clearance-based measured glomerular filtration rate (mGFR) decline (>10% per year) in a subsample of 229 CKD patients (mean age, 61 years; 66% men; baseline mGFR, 38 mL/min) from the NephroTest prospective cohort. Findings: Among the 30 assays, directed against 24 candidate biomarkers, encompassing different pathophysiological mechanisms of CKD progression, 16 assays fulfilled the FDA-approved criteria. LASSO logistic regressions identified a combination of five biomarkers including CCL2, EGF, KIM1, NGAL, and TGF-α that improved the prediction of fast mGFR decline compared to the kidney failure risk equation variables alone: age, gender, mGFR, and albuminuria. Mean area under the curves (AUC) estimated from 100 re-samples was higher in the model with than without these biomarkers, 0.722 (95% confidence interval 0.652–0.795) vs. 0.682 (0.614–0.748), respectively. Fully-adjusted odds-ratios (95% confidence interval) for fast progression were 1.87 (1.22, 2.98), 1.86 (1.23, 2.89), 0.43 (0.25, 0.70), 1.10 (0.71, 1.83), 0.55 (0.33, 0.89), and 2.99 (1.89, 5.01) for albumin, CCL2, EGF, KIM1, NGAL, and TGF-α, respectively. Interpretation: This study provides a rigorous validation of multiple assays for relevant urinary biomarkers of CKD progression which combination may improve the prediction of CKD progression. Funding: This work was supported by Institut National de la Santé et de la Recherche Médicale, Université de Paris, Assistance Publique Hôpitaux de Paris, Agence Nationale de la Recherche, MSDAVENIR, Pharma Research and Early Development Roche Laboratories (Basel, Switzerland), and Institut Roche de Recherche et Médecine Translationnelle (Paris, France).
Published: 2023
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7. Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin–angiotensin system blocker

Author: Jean-Philippe Haymann, Nadjib Hammoudi, Marine Livrozet, Aline Santin, Sarah Mattioni, Emmanuel Letavernier, Vincent Frochot, Camille Saint Jacques, Olivier Steichen, Gilles Grateau, Michel Chaignon, and François Lionnet
Subjects: Medicine, Science
Abstract: Abstract Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (
Published: 2021
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8. Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model

Author: Héloïse Bilbault, Joëlle Perez, Léa Huguet, Sophie Vandermeersch, Sandrine Placier, Nahid Tabibzadeh, Vincent Frochot, Emmanuel Letavernier, Dominique Bazin, Michel Daudon, and Jean-Philippe Haymann
Subjects: Urothelial Cell Proliferation, Crystal Deposition, FGF7 Groups, FGF7 Administration, Crystal Retention, Medicine, Science
Abstract: Abstract Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.
Published: 2018
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9. Specific calpain inhibition protects kidney against inflammaging

Author: Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, and Emmanuel Letavernier
Subjects: Medicine, Science
Abstract: Abstract Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice. In addition, we analysed inflammatory response in the kidney of aged CalpTG and wild-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation. At two years, CalpTG mice had preserved kidney tissue, less vascular remodelling and less markers of senescence than wild-type mice. Nevertheless, CalpTG mice lifespan was not extended, due to the development of lethal spleen tumors. Inflammatory pathways were less expressed in aged CalpTG mice, especially cytokines related to NF-κB and NLRP3 inflammasome activation. CalpTG mice had reduced macrophage infiltration with aging and CalpTG mice produced less IL-1α and IL-1β in vivo in response to inflammasome activators. In vitro, macrophages from CalpTG mice produced less IL-1α in response to particulate activators of inflammasome. Calpains inhibition protects against inflammaging, limiting kidney and vascular lesions related to aging.
Published: 2017
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10. Localization and characterization of thyroid microcalcifications: A histopathological study.

Author: Joanne Guerlain, Sophie Perie, Marine Lefevre, Joëlle Perez, Sophie Vandermeersch, Chantal Jouanneau, Léa Huguet, Vincent Frochot, Emmanuel Letavernier, Raphael Weil, Stéphan Rouziere, Dominique Bazin, Michel Daudon, and Jean-Philippe Haymann
Subjects: Medicine, Science
Abstract: Thyroid calcification is frequent in thyroid nodules. The aim of our study was to evaluate the prevalence of calcifications in thyroid tissue samples of patients with various thyroid diseases, and to identify their composition according to their localization. Among 50 thyroid samples included, 56% were malignant (papillary carcinoma) and 44% were benign (adenoma, multinodular goiter, Graves' disease, sarcoidosis). Calcifications were found in 95% of samples using polarised light microscopy, whereas only 12% were described in initial pathological reports. Three types were individualised and analyzed by infrared spectrometry (μFTIR): colloid calcifications composed of calcium oxalate, capsular calcifications and psammoma bodies, both composed of calcium phosphate. Of notice, psammoma bodies characterized by FE-SEM were composed of concentric structure suggesting a slow process for crystal deposition. Calcium phosphates were found only in malignant samples whereas calcium oxalate was not associated with a define pathology. Proliferation assessed by KI67 staining was high (33% of positive follicles), and RUNX2, OPN, and CD44 positive staining were detected in thyrocytes with a broad variation between samples. However, thyrocyte proliferation and differentiation markers were not associated with the number of crystals. TRPV5 and CaSR expression was also detected in thyrocytes. mRNA transcripts expression was confirmed in a subgroup of 10 patients, altogether with other calcium transporters such as PMCA1 or Cav1.3. Interestingly, TRPV5 mRNA expression was significantly associated with number of colloid calcifications (rho = -0.72; p = 0.02). The high prevalence of calcium oxalate crystals within colloid gel raises intriguing issues upon follicle physiology for calcium and oxalate transport.
Published: 2019
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11. From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients.

Author: Lynda Cheddani, Camélia Radulescu, Michel Chaignon, Alexandre Karras, Yann Neuzillet, Jean-Paul Duong, Nahid Tabibzadeh, Emmanuel Letavernier, Michel Delahousse, and Jean-Philippe Haymann
Subjects: Medicine, Science
Abstract: Aortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters.The study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis.After a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD.Aortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.
Published: 2018
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12. An animal model of type A cystinuria due to spontaneous mutation in 129S2/SvPasCrl mice.

Author: Marine Livrozet, Sophie Vandermeersch, Laurent Mesnard, Elizabeth Thioulouse, Jean Jaubert, Jean-Jacques Boffa, Jean-Philippe Haymann, Laurent Baud, Dominique Bazin, Michel Daudon, and Emmanuel Letavernier
Subjects: Medicine, Science
Abstract: Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.
Published: 2014
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13. The calpain/calpastatin system has opposing roles in growth and metastatic dissemination of melanoma.

Author: Quentin Raimbourg, Joëlle Perez, Sophie Vandermeersch, Aurélie Prignon, Guillaume Hanouna, Jean-Philippe Haymann, Laurent Baud, and Emmanuel Letavernier
Subjects: Medicine, Science
Abstract: Conventional calpains are ubiquitous cysteine proteases whose activity is promoted by calcium signaling and specifically limited by calpastatin. Calpain expression has been shown to be increased in human malignant cells, but the contribution of the calpain/calpastatin system in tumorigenesis remains unclear. It may play an important role in tumor cells themselves (cell growth, migration, and a contrario cell death) and/or in tumor niche (tissue infiltration by immune cells, neo-angiogenesis). In this study, we have used a mouse model of melanoma as a tool to gain further understanding of the role of calpains in tumor progression. To determine the respective importance of each target, we overexpressed calpastatin in tumor and/or host in isolation. Our data demonstrate that calpain inhibition in both tumor and host blunts tumor growth, while paradoxically increasing metastatic dissemination to regional lymph nodes. Specifically, calpain inhibition in melanoma cells limits tumor growth in vitro and in vivo but increases dissemination by amplifying cell resistance to apoptosis and accelerating migration process. Meanwhile, calpain inhibition restricted to host cells blunts tumor infiltration by immune cells and angiogenesis required for antitumor immunity, allowing tumor cells to escape tumor niche and disseminate. The development of highly specific calpain inhibitors with potential medical applications in cancer should take into account the opposing roles of the calpain/calpastatin system in initial tumor growth and subsequent metastatic dissemination.
Published: 2013
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14. Renal function can improve at any stage of chronic kidney disease.

Author: Lise Weis, Marie Metzger, Jean-Philippe Haymann, Eric Thervet, Martin Flamant, François Vrtovsnik, Cédric Gauci, Pascal Houillier, Marc Froissart, Emmanuel Letavernier, Bénédicte Stengel, Jean-Jacques Boffa, and NephroTest Study Group
Subjects: Medicine, Science
Abstract: INTRODUCTION: Even though renal function decline is considered relentless in chronic kidney disease (CKD), improvement has been shown in patients with hypertensive nephropathy. Whether this can occur in any type of nephropathy and at any stage is unknown as are the features of patients who improve. METHODS: We identified 406 patients in the NephroTest cohort with glomerular filtration rates (mGFR) measured by (51)Cr-EDTA clearance at least 3 times during at least 2 years of follow-up. Individual examination of mGFR trajectories by 4 independent nephrologists classified patients as improvers, defined as those showing a sustained mGFR increase, or nonimprovers. Twelve patients with erratic trajectories were excluded. Baseline data were compared between improvers and nonimprovers, as was the number of recommended therapeutic targets achieved over time (specifically, for systolic and diastolic blood pressure, proteinuria, and use of renin angiotensin system blockers). RESULTS: Measured GFR improved over time in 62 patients (15.3%). Their median mGFR slope was +1.88[IQR 1.38, 3.55] ml/min/year; it was -2.23[-3.9, -0.91] for the 332 nonimprovers. Improvers had various nephropathies, but not diabetic glomerulopathy or polycystic kidney disease. They did not differ from nonimprovers for age, sex, cardiovascular history, or CKD stage, but their urinary albumin excretion rate was lower. Improvers achieved significantly more recommended therapeutic targets (2.74±0.87) than nonimprovers (2.44±0.80, p
Published: 2013
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15. Calpain activity is essential in skin wound healing and contributes to scar formation.

Author: Dany Nassar, Emmanuel Letavernier, Laurent Baud, Selim Aractingi, and Kiarash Khosrotehrani
Subjects: Medicine, Science
Abstract: Wound healing is a multistep phenomenon that relies on complex interactions between various cell types. Calpains are ubiquitously expressed proteases regulating several processes including cellular adhesion and motility as well as inflammation and angiogenesis. Calpains can be targeted by inhibitors, and their inhibition was shown to reduce organ damage in various disease models. We aimed to assess the role of calpains in skin healing and the potential benefit of calpain inhibition on scar formation. We used a pertinent model where calpain activity is inhibited only in lesional organs, namely transgenic mice overexpressing calpastatin (CPST), a specific natural calpain inhibitor. CPST mice showed a striking delay in wound healing particularly in the initial steps compared to wild types (WT). CPST wounds displayed reduced proliferation in the epidermis and delayed re-epithelization. Granulation tissue formation was impaired in CPST mice, with a reduction in CD45+ leukocyte infiltrate and in CD31+ blood vessel density. Interestingly, wounds on WT skin grafted on CPST mice (WT/CPST) showed a similar delayed healing with reduced angiogenesis and inflammation compared to wounds on WT/WT mice demonstrating the implication of calpain activity in distant extra-cutaneous cells during wound healing. CPST wounds showed a reduction in alpha-smooth muscle actin (αSMA) expressing myofibroblasts as well as αSMA RNA expression suggesting a defect in granulation tissue contraction. At later stages of skin healing, calpain inhibition proved beneficial by reducing collagen production and wound fibrosis. In vitro, human fibroblasts exposed to calpeptin, a pan-calpain inhibitor, showed reduced collagen synthesis, impaired TGFβ-induced differentiation into αSMA-expressing myofibroblasts, and were less efficient in a collagen gel contraction assay. In conclusion, calpains are major players in granulation tissue formation. In view of their specific effects on fibroblasts a late inhibition of calpains should be considered for scar reduction.
Published: 2012
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16. Chronic urine acidification by fludrocortisone to treat infectious kidney stones

Author: Arnaud Lionet, Michel Daudon, Xavier Biardeau, Emmanuel Letavernier, and Camille Roger
Subjects: medicine.medical_specialty, business.industry, Fludrocortisone, Urology, medicine, Kidney stones, Building and Construction, Urine, Electrical and Electronic Engineering, medicine.disease, business, medicine.drug
Published: 2022

17. Lateralization of uric acid stones on the left side

Author: Claude Marsault, Michel Daudon, Guillaume Müller, Jonathan Cloutier, Olivier Traxer, Martin Flamant, Luca Villa, Jean-Philippe Haymann, and Emmanuel Letavernier
Subjects: medicine.medical_specialty, business.industry, Urology, Medicine, Uric acid stones, Building and Construction, Electrical and Electronic Engineering, business, Lateralization of brain function
Published: 2022

18. Risk factors for <scp>CKD</scp> stage <scp>II</scp> onset in a prospective cohort of homozygous sickle cell adults

Author: V. Avellino, Olivier Steichen, Nadjib Hammoudi, Marine Livrozet, S. Mattioni, Camille Roger, François Lionnet, Jean-Philippe Haymann, Emmanuel Letavernier, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Blood Pressure, Anemia, Sickle Cell, urologic and male genital diseases, Sickle cell nephropathy, Young Adult, Risk Factors, Internal medicine, medicine, Albuminuria, Humans, Prospective Studies, Renal Insufficiency, Chronic, Risk factor, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, business.industry, Incidence, Age Factors, Hematology, medicine.disease, Sickle cell anemia, Blood pressure, Cohort, Female, Microalbuminuria, business, Glomerular Filtration Rate, Cohort study
Abstract: Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients responsible for a high morbidity and mortality. However, sickle cell nephropathy natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using Cox model. 535 SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mmHg HR: 2.02 [1.02-3.971], LDH (for 100 UI/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20- 6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3 fold increase above 30 years (p
Published: 2021

19. Effet du stiripentol sur l’excrétion urinaire d’oxalate

Author: Michel Daudon and Emmanuel Letavernier
Subjects: Kidney, Chemistry, 030232 urology & nephrology, Calcium oxalate, Pharmacology, medicine.disease, Oxalate, Primary hyperoxaluria, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine.anatomical_structure, Ethylene glycol poisoning, Nephrology, Lactate dehydrogenase, medicine, Stiripentol, medicine.drug
Abstract: Oxalate is a metabolite promoting the formation of calcium oxalate crystals in urine. Hyperoxaluria is a feature of genetic diseases, known as primary hyperoxaluria, leading to chronic kidney disease. Ethylene glycol poisoning induces the crystallization of calcium oxalate crystals in renal tubules, promoting acute renal failure. Urine oxalate results from glyoxylate transformation to oxalate in the liver, due to lactate dehydrogenase (LDH) activity, especially the LDH-5 isoenzyme. Genetic RNA interference therapy targeting lactate dehydrogenase lowers urine oxalate excretion in murine models. Stiripentol is a drug inhibiting neuronal LDH-5 isoenzyme activity. We hypothesized that stiripentol would also reduce hepatic oxalate production and urine oxalate excretion. In vitro Stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol decreases urine oxalate excretion in rats and protects kidney tissue and function against ethylene glycol intoxication and hydroxyproline-induced calcium oxalate crystalline nephropathy. The use of stiripentol in clinical practice deserves further clinical studies.
Published: 2021

20. Reply to: 'Progressive cholangiopathy in COVID-19 patients: Other possible diagnoses than ketamine-induced cholangiopathy should be considered'

Author: Vincent Mallet, Kilian Bock, Mourad Dellagi, Marion Tano, Virginie Siorat, Nathanaël Beeker, Pascal Paubel, Paul Doumbe Mandengue, Nicolas Dufour, Torsten Voigtländer, Jean-Damien Ricard, Pierre Isnard, Vincent Frochot, Emmanuel Letavernier, Lucile Moga, Amandine Landrieux, Pierre-Emmanuel Rautou, Nathalie Pons-Kerjean, Anaïs Vallet-Pichard, Clémence Hollande, Hélène Fontaine, Laurent Chouchana, Coralie Gernez, Carole Burger, Anne Scemla, Christian de Tymowski, François Depret, Emmanuel Dudoignon, Lionel Lamhaut, Rémi Flicoteau, Géraldine Rousseau, Jean-Paul Duong Van Huyen, Jean-Michel Correas, Heiner Wedemeyer, and Stanislas Pol
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Hepatology, Coronavirus disease 2019 (COVID-19), medicine.diagnostic_test, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, Gastroenterology, Cholestasis, Internal medicine, medicine, Ketamine, Bile Duct Diseases, Liver function tests, business, medicine.drug
Published: 2021

21. Effect of parathyroidectomy on renal stone recurrence

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Pierre-Yves Charles, Michel Daudon, Sophie Périé, and Mathieu Gauthé
Subjects: Adult, Male, Nephrology, Parathyroidectomy, medicine.medical_specialty, Urology, medicine.medical_treatment, 030232 urology & nephrology, Parathyroid hormone, Diuresis, Urine, Kidney Calculi, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Hypercalciuria, Calcium metabolism, business.industry, Middle Aged, Hyperparathyroidism, Primary, medicine.disease, Female, business, Primary hyperparathyroidism
Abstract: Parathyroidectomy (PTX) is routinely performed in hypercalciuric renal stone patients with primary hyperparathyroidism (PHPT). However, some data indicate a persistent stone activity following PTX, raising the issue of the link between PHPT and stone disease. We performed an observational study on 30 renal stone patients diagnosed with PHPT. Patients were selected among 1448 hypercalciuric patients referred in our department for a diagnostic evaluation. Patients with no parathyroid surgery or any biological follow-up were excluded. Clinical and biological data (including 24-h urine collection and a calcium load test) were collected before and within 12 months following surgery. Stone recurrence was evaluated by direct phone contact (median 43 months). Comparison of biological data before and after surgery showed a significant decrease of ionized calcium and serum parathyroid hormone after PTX. All stones contained calcium-dependent species such as carbapatite, brushite or dihydrate calcium oxalate. Urine saturation indexes and calciuria significantly decreased after surgery (from 9.9 to 5.9 mmol/d, p
Published: 2021

22. A cross-sectional study of 502 patients found a diffuse hyperechoic kidney medulla pattern in patients with severe gout

Author: N.H. Le, Thomas Bardin, Khoy M. Tran, Quang D. Nguyen, Pascal Richette, Mathieu Resche-Rigon, Jean-Michel Correas, Minh Duc Do, Emmanuel Letavernier, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de radiologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: musculoskeletal diseases, 0301 basic medicine, renal ultrasonography, medicine.medical_specialty, estimated glomerular filtration rate, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Renal function, Hyperuricemia, MESH: Uric Acid, Nephropathy, 03 medical and health sciences, gout, MESH: Cross-Sectional Studies, 0302 clinical medicine, Arthropathy, medicine, Humans, MESH: Kidney Medulla, Kidney Medulla, Univariate analysis, microcrystalline nephropathy, MESH: Humans, Proteinuria, business.industry, MESH: Gout, Echogenicity, MESH: Hyperuricemia, medicine.disease, Uric Acid, 3. Good health, Gout, Cross-Sectional Studies, 030104 developmental biology, Nephrology, medicine.symptom, business, chronic kidney disease
Abstract: International audience; We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria) at the Vien Gut medical center in Ho Chi Minh City, Vietnam. None of these patients received urate-lowering drugs. Kidney medulla echogenicity on B-mode ultrasonography was compared to that of the kidney cortex. Overall, 36% patients showed a hyperechoic pattern of Malpighi pyramids. On univariate analysis, the pattern was significantly associated with age, estimated gout duration, steroid-dependency, clinical tophi, urate arthropathy, double contour thickness at the scanned joints, coronary heart disease, arterial hypertension, hyperuricemia, proteinuria, leukocyturia, and decreased estimated glomerular filtration rate. On multivariable analysis, the hyperechoic pattern was associated with estimated disease duration, clinical tophi, urate arthropathy, double contour thickness and decreased estimated glomerular filtration rate. No hyperechoic pattern was observed in 515 consecutive consultants without gout. Thus, hyperechoic kidney medulla was frequently demonstrated in Vietnamese patients with tophaceous gout and associated with features of tubulointerstitial nephritis. This finding revives the hypothesis of microcrystalline nephropathy of gout, predominantly seen in untreated gouty patients, which could be an important target for urate-lowering therapy.
Published: 2021

23. 1-Methyluric Acid Nephropathy

Author: E. Bouderlique, Dominique Bazin, Jean-Paul Duong Van Huyen, Vincent Frochot, Michel Daudon, Jean-Philippe Haymann, Emmanuel Letavernier, Dany Anglicheau, Yann Neugebauer, Viviane Gnemmi, Jeremy Zaworski, Jean-Baptiste Gibier, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie et Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie et dialyse, Centre Hospitalier de Douai, Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, 1-methyluric acid, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, medicine.disease, Gastroenterology, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Internal medicine, Research Letter, Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

24. Nanoscale Analysis of Randall’s Plaques by Electron Energy Loss Spectromicroscopy: Insight in Early Biomineral Formation in Human Kidney

Author: Michael Walls, Dominique Bazin, Marie-Christine Verpont, Marta de Frutos, Odile Stéphan, Nadine Nassif, Emmanuel Letavernier, Michel Daudon, Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matériaux Hybrides et Procédés (LCMCP-MHP ), Matériaux Hybrides et Nanomatériaux (LCMCP-MHN), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), and Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Calcium Phosphates, kidney, Surface Properties, [SDV]Life Sciences [q-bio], calcium carbonate nanoparticles, General Physics and Astronomy, chemistry.chemical_element, Electrons, Spectroscopy, Electron Energy-Loss, 02 engineering and technology, Calcium, 010402 general chemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 01 natural sciences, Kidney Calculi, chemistry.chemical_compound, calcium phosphate nanoparticles, medicine, Humans, Nanotechnology, General Materials Science, Particle Size, electron energy-loss spectroscopy, [PHYS]Physics [physics], Kidney Medulla, Biomineral formation, Electron energy, Vesicle, General Engineering, Human kidney, biomineralization, 021001 nanoscience & nanotechnology, medicine.disease, 0104 chemical sciences, chemistry, Biophysics, Carbonate, Randall’s plaques, 0210 nano-technology, Biomineralization, Calcification
Abstract: International audience; Idiopathic kidney stones originate mainly from calcium phosphate deposits at the tip of renal papillae, known as Randall’s plaques (RPs), also detected in most human kidneys without stones. However, little is known about the mechanisms involved in RP formation. The localization and characterization of such nano-sized objects in the kidney remains a real challenge making their study arduous. This study provides a nanoscale analysis of the chemical composition and morphology of incipient RPs, characterizing in particular the interface between the mineral and the surrounding organic compounds. Relying on data gathered from a calculi collection, the morphology and chemical composition of incipient calcifications in renal tissue was determined using spatially resolved electron energy-loss spectroscopy (EELS). We detected micro-calcifications and individual nano-calcifications found at some distance from the larger ones. Strikingly, concerning the smaller ones, we show that two types of nano-calcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nano-calcifications present similarities with those reported in physiological bone or pathological cardiovascular biominerals, suggesting possible common formation mechanisms. However the high diversity of these nano-calcifications suggests that several mechanisms may be involved (nucleation on a carbonate core or on organic compounds). In addition, incipient RPs also appear to present specific features at larger scales revealing secondary calcified structures embedded in a fibrillar organic material. Our study proves that analogies exist between physiological and pathological biominerals and provides information to understand the physico-chemical processes involved in pathological calcification formation.
Published: 2020

25. Randall's plaque as the origin of idiopathic calcium oxalate stone formation: an update

Author: Michel Daudon, Karl Martin Wissing, Elise Bouderlique, Emmanuel Letavernier, Els Van de Perre, Dominique Bazin, Vincent Estrade, Internal Medicine, Nephrology, Chemistry, Faculty of Arts and Philosophy, Clinical sciences, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Stone formation, Calcium oxlate stones, kidney stones, 030232 urology & nephrology, Calcium oxalate, Building and Construction, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, chemistry, Randall's plaque, Calcium phosphate, Calcium oxalate stones, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Internal medicine, Nephrolithi-asis, medicine, Electrical and Electronic Engineering, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, nephrolithiasis
Abstract: The majority of idiopathic calcium oxalate kidney stones form on the Randall's plaque, a subepithelial calcium phosphate plaque at the renal papilla. The formation mechanisms of the Ran-dall's plaque and associated calcium oxalate stones remain incompletely understood. This article pro-vides an historical overview of the research performed on this topic, describes the current epidemi-ological trends of Randall's plaque-associated kidney stone formation and reviews the suggested for-mation mechanisms of Randall's plaque and associated calcium oxalate stones. Finally, this overview highlights the recent advances made on the subject, including the development of an animal model.
Published: 2022

26. Calcinosis cutis in epidermal necrolysis: role of caspofungin?

Author: Emmanuel Letavernier, N. de Prost, Philippe Moguelet, Dominique Bazin, Hester Colboc, A. Boury, T. Bettuzzi, Vincent Frochot, Saskia Ingen-Housz-Oro, Nicolas Ortonne, Ellie Tang, and Marine Badrignans
Subjects: 0303 health sciences, medicine.medical_specialty, Skin Neoplasms, business.industry, Calcinosis, Dermatology, medicine.disease, 01 natural sciences, Skin Diseases, 010309 optics, Calcinosis cutis, 03 medical and health sciences, chemistry.chemical_compound, Infectious Diseases, chemistry, Epidermal necrolysis, Caspofungin, Stevens-Johnson Syndrome, 0103 physical sciences, medicine, Humans, business, 030304 developmental biology
Published: 2021

27. Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

Author: Edmat Akhtar Khan, Rosa Vargas-Poussou, Remi Chieze, Lynda Cheddani, Jean-Philippe Haymann, Vincent Frochot, Emmanuel Letavernier, Camille Saint-Jacques, V. Avellino, François Lionnet, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Calcitriol, endocrine system diseases, chemistry.chemical_element, familial hypocalciuric hypercalcemia, Calcium, Asymptomatic, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, FeCa2+, Internal medicine, hemic and lymphatic diseases, medicine, Hypercalciuria, 030212 general & internal medicine, primary hyperparathyroidism, 030304 developmental biology, Calcium metabolism, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Familial hypocalciuric hypercalcemia, business.industry, General Medicine, medicine.disease, Urinary calcium, 3. Good health, chemistry, Medicine, sickle cell disease, medicine.symptom, hemolysis, business, Primary hyperparathyroidism, urinary calcium, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients, (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT, (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p &lt, 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.
Published: 2021

28. Calcified leg Ulcers in older patients: clinical description, morphology and chemical characterization

Author: Michel Daudon, Dominique Bazin, Michael Reby, Naomi Laporte, Stéphan Rouzière, Juliette Fontaine, Hester Colboc, Agnès Galezowski, Christine Forasassi, Emmanuel Letavernier, Sylvie Meaume, Vincent Frochot, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: Aging, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Gastroenterology, Palpation, Varicose Ulcer, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Dystrophic calcification, Bacterial colonization, Older patients, Internal medicine, medicine, Humans, Rothschild, Prospective Studies, Aged, medicine.diagnostic_test, business.industry, Field emission scanning electron microscopy, Leg Ulcer, medicine.disease, 3. Good health, Leg ulcer, Venous Insufficiency, Calcium, Geriatrics and Gerontology, business
Abstract: Chronic wounds, including leg ulcers, constitute an important medical problem among older patients. Dystrophic calcifications (DC) are associated with a variety of disorders, including leg ulcers. The aim of this study was to report the clinical and biological characteristics of older patients with DC in leg ulcers and to determine the morphology and chemical composition of these calcifications. We conducted a prospective monocentric study in our Geriatric-Wound and Healing ward, Rothschild Hospital, Paris, from January 2018 to December 2019. Patients with leg ulcers were screened for DC by palpation. Patients’ clinical, biological, and radiological findings were collected. DC morphology was analyzed using field-emission scanning electron microscopy and chemical composition was analyzed using µFourier transform infra-red spectroscopy and X-ray Fluorescence. Ten (7%) of the 143 patients hospitalized for leg ulcers presented DC. Older patients with DC were more likely to have leg ulcers with venous insufficiency (p = .015), colonized by Pseudomonas aeruginosa (p = .026), with a longer healing evolution (p = .0072) and hypercalcemia (p = .041). Five DC were extracted from ulcers: 2 presented 500 nm lacunar spheres and intermingled fibrils of about 10 nm in diameter, consistent with bacterial and biofilm imprints. DC were always composed of calcium–phosphate apatite and associated to the presence of zinc. Our analyses were consistent with the involvement of microorganisms and inflammatory process in DC formation. Early management of venous insufficiency, treatment of chronic bacterial colonization and use of calcium-solubilizing drugs seem to be rational strategies for calcified leg ulcer management in older patients.
Published: 2021

29. 'Trust my morphology', the key message from a kidney stone

Author: Emmanuel Letavernier, James C. Williams, Carl Van Haute, Naim M. Maalouf, Agnieszka Pozdzik, Khashayar Sakhaee, Ecole de Santé Publique [Université Libre de Bruxelles], Université libre de Bruxelles (ULB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Texas Southwestern Medical Center [Dallas], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Indiana University School of Medicine, and Indiana University System
Subjects: Nephrology, Crystalluria, medicine.medical_specialty, Consensus, Urology, 030232 urology & nephrology, MEDLINE, Morphology (biology), Urine analysis, Urinalysis, 030204 cardiovascular system & hematology, Trust, Nephrolithiasis, Specimen Handling, Kidney Calculi, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, Internal medicine, medicine, Humans, Intensive care medicine, Letter to the Editor, Invited Review, Calcium Oxalate, business.industry, medicine.disease, RENAL PHARMACOLOGY, 3. Good health, Key (cryptography), Kidney stones, Stone analysis, Crystallization, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places. Electronic supplementary material The online version of this article (10.1007/s00240-020-01217-3) contains supplementary material, which is available to authorized users.
Published: 2021

30. Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin–angiotensin system blocker

Author: Vincent Frochot, Gilles Grateau, Michel Chaignon, Olivier Steichen, Marine Livrozet, Aline Santin, S. Mattioni, Jean-Philippe Haymann, Emmanuel Letavernier, François Lionnet, Nadjib Hammoudi, Camille Saint Jacques, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Physiology, Science, Kidney Glomerulus, Hydrostatic pressure, Cardiac index, Renal function, Angiotensin-Converting Enzyme Inhibitors, Anemia, Sickle Cell, 030204 cardiovascular system & hematology, Article, Nephropathy, Renin-Angiotensin System, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, business.industry, Hemodynamics, medicine.disease, 3. Good health, Treatment Outcome, medicine.anatomical_structure, Nephrology, Renal blood flow, Vascular resistance, Albuminuria, Cardiology, Medicine, Female, Kidney Diseases, medicine.symptom, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Glomerular hyperfiltration, Glomerular Filtration Rate, 030215 immunology
Abstract: Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (−5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: − 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.
Published: 2021

31. Prevalence and identification of crystalluria in critically ill patients: association between uric acid crystals and sepsis

Author: Benjamin G. Chousterman, Thibault Michel, Jean-Philippe Haymann, Nahid Tabibzadeh, Michel Daudon, Emmanuel Letavernier, Alexandre Mebazaa, Antoine Borouchaki, Vincent Frochot, Maxime Zalc, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, Hal Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 030203 arthritis & rheumatology, Transplantation, medicine.medical_specialty, Critically ill, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Sepsis, Uric acid crystals, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Internal medicine, medicine, Crystalluria, Identification (biology), medicine.symptom, Letters to the Editor, AcademicSubjects/MED00340, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

32. Amoxicillin crystalluria is associated with acute kidney injury in patients treated for acute infective endocarditis

Author: Julien Ternacle, Nicolas Mongardon, Sovannarith San, Michel Daudon, Jean-Philippe Haymann, Emmanuel Letavernier, Pascal Lim, Antonio Fiore, Amina Moussafeur, Raphaël Lepeule, Leopold Oliver, Matthieu Jamme, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Henri Mondor, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Nephrolithiasis, Amoxicillin, Anti-Bacterial Agents, Humans, Acute Kidney Injury, Endocarditis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Crystalluria, Acute infective endocarditis, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Transplantation, business.industry, Acute kidney injury, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, medicine.symptom, business, medicine.drug
Abstract: International audience
Published: 2021

33. Acute Kidney Injury After High Doses of Amoxicillin

Author: Yosu Luque, Valérie Zeller, Cédric Rafat, Younes Kerroumi, Emmanuel Letavernier, Cyril Mousseaux, Vincent Frochot, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe Hospitalier Diaconesses Croix Saint-Simon, Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0303 health sciences, medicine.medical_specialty, 030306 microbiology, business.industry, [SDV]Life Sciences [q-bio], Acute kidney injury, Amoxicillin, medicine.disease, Gastroenterology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Text mining, Nephrology, Internal medicine, medicine, High doses, Research Letter, 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: International audience
Published: 2021

34. The Case | Isolated microscopic hematuria: a diagnostic journey

Author: Laure Raymond, Nicolas Benichou, Laurent Mesnard, Hélène François, and Emmanuel Letavernier
Subjects: Pathology, medicine.medical_specialty, Nephrology, business.industry, Humans, Medicine, Microscopic hematuria, business, Hematuria
Published: 2021

35. Encrusted Uropathy

Author: Els Van de Perre, Gina Reichman, Deborah De Geyter, Caroline Geers, Karl M. Wissing, Emmanuel Letavernier, Nephrology, Medicine and Pharmacy academic/administration, Movement and Sport Sciences, Basic (bio-) Medical Sciences, Experimental Pharmacology, Microbiology and Infection Control, Clinical Biology, Laboratory for Medical and Molecular Oncology, Pathology, Clinical sciences, Vrije Universiteit Brussel [Bruxelles] (VUB), Vrije Universiteit Brussel (VUB), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Gestionnaire, HAL Sorbonne Université 5, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Corynebacterium urealyticum, Pathology, medicine.medical_specialty, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Urinary system, ved/biology.organism_classification_rank.species, 030232 urology & nephrology, Review, Timely diagnosis, 03 medical and health sciences, 0302 clinical medicine, encrusted cystitis, Antibiotic therapy, encrusted pyelitis, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, In patient, Urothelium, urease-producing bacteria, lcsh:R5-920, Uropathy, business.industry, ved/biology, encrusted uropathy, General Medicine, medicine.disease, Chronic inflammatory disorder, 3. Good health, Nephrology, 030220 oncology & carcinogenesis, lcsh:Medicine (General), business
Abstract: Encrusted uropathy is a rare subacute to chronic inflammatory disorder caused by infection with urease-producing bacteria, mainlyCorynebacterium urealyticum. The disorder is characterized by urothelial deposition of struvite and carbonated apatite, resulting in encrustations and ulceronecrotic inflammation of the urothelium and surrounding tissues. Most commonly, encrusted uropathy is encountered in patients with predisposing conditions. The disease remains underdiagnosed. High urinary pH and negative conventional urine cultures should raise suspicion of the diagnosis. Prognosis is dependent on timely diagnosis and treatment installment, which consists of urological removal of encrustations in combination with urinary acidification and long-term antibiotic therapy.
Published: 2021

36. Urine and stone analysis for the investigation of the renal stone former: a consensus conference

Author: Hans Göran Tiselius, Pietro Manuel Ferraro, Felix Grases, Olivier Traxer, John R. Asplin, Ita Pfeferman Heilberg, Giuseppe Lippi, Daniel Guido Fuster, Giovanni Gambaro, James C. Williams, Olivier Bonny, Michele Petrarulo, Alberto Trinchieri, Giovanni B. Fogazzi, Antonia Costa-Bauzá, Dik Kok, David S. Goldfarb, Antonio Nouvenne, Martino Marangella, Emanuele Croppi, Allen L. Rodgers, Emmanuel Letavernier, William G. Robertson, Roswitha Siener, Indiana University School of Medicine, Indiana University System, University of Verona (UNIVR), University of Cape Town, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of the Balearic Islands (UIB), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Università cattolica del Sacro Cuore [Roma] (Unicatt), Bern University Hospital [Berne] (Inselspital), Universidade Federal de São Paulo, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Parma = Università degli studi di Parma [Parme, Italie], University Hospital Bonn, Karolinska Institutet [Stockholm], Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Milan, and University of Oxford [Oxford]
Subjects: Nephrology, medicine.medical_specialty, Crystalluria, Urology, Urinary stone, 030232 urology & nephrology, 610 Medicine & health, Urine, Urine analysis, Stone analysis, Nephrolithiasis, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Settore MED/14 - NEFROLOGIA, Intensive care medicine, Renal stone, business.industry, Consensus conference, Crystalluria, Nephrolithiasis, Stone analysis,Urine analysis, 3. Good health, 030220 oncology & carcinogenesis, medicine.symptom, business, Patient education
Abstract: The Consensus Group deliberated on a number of questions concerning urine and stone analysis over a period of months, and then met to develop consensus. The Group concluded that analyses of urine and stones should be routine in the diagnosis and treatment of urinary stone diseases. At present, the 24-h urine is the most useful type of urine collection, and accepted methods for analysis are described. Patient education is also important for obtaining a proper urine sample. Graphical methods for reporting urine analysis results can be helpful both for the physician and for educating the patient as to proper dietary changes that could be beneficial. Proper analysis of stones is also essential for diagnosis and management of patients. The Consensus Group also agreed that research has shown that evaluation of urinary crystals could be very valuable, but the Group also recognizes that existing methods for assessment of crystalluria do not allow this to be part of stone treatment in many places., This article is based on the results of a Consensus Conference held during the 4th INTERNATIONAL MEETING OF THE MENARINI FOUNDATION ON NEPHROLITHIASIS, Verona, June 20-22, 2019 generously supported by the International Foundation Menarini, Milan, Italy with an unrestricted educational Grant.
Published: 2021

37. In search of an efficient complexing agent for oxalates and phosphates : a quantum chemical study

Author: Javier Torres, Karl Martin Wissing, Jelle Vekeman, Cristina David, Michel Daudon, Emmanuel Letavernier, Agnieszka Pozdzik, Frederik Tielens, Els Van de Perre, Dominique Bazin, Chemistry, Nephrology, Clinical sciences, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: inorganic chemicals, phosphates, [SDV]Life Sciences [q-bio], complexation, General Chemical Engineering, 030232 urology & nephrology, nephrology, 02 engineering and technology, Chloride, DFT, Oxalate, Article, 03 medical and health sciences, chemistry.chemical_compound, Hyperphosphatemia, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, medicine, Formate, Chelation, General Materials Science, oxalates, QD1-999, 021001 nanoscience & nanotechnology, medicine.disease, Phosphate, 3. Good health, Chemistry, chemistry, Physics and Astronomy, Hydroxide, 0210 nano-technology, Enteric Hyperoxaluria, medicine.drug, Nuclear chemistry
Abstract: Limiting gastrointestinal oxalate absorption is a promising approach to reduce urinary oxalate excretion in patients with idiopathic and enteric hyperoxaluria. Phosphate binders, that inhibit gastrointestinal absorption of dietary phosphate by the formation of easily excretable insoluble complexes, are commonly used as a treatment for hyperphosphatemia in patients with end-stage renal disease. Several of these commercially available phosphate binders also have affinity for oxalate. In this work, a series of metallic cations (Li+, Na+, Mg2+, Ca2+, Fe2+, Cu2+, Zn2+, Al3+, Fe3+ and La3+) is investigated on their binding affinity to phosphate and oxalate on one side and anionic species that could be used to administer the cationic species to the body on the other, e.g., acetate, carbonate, chloride, citrate, formate, hydroxide and sulphate. Through quantum chemical calculations, the aim is to understand the competition between the different complexes and propose possible new and more efficient phosphate and oxalate binders.
Published: 2021

38. Inflammation plays a critical role in 2,8-dihydroxyadenine nephropathy

Author: Dominique Bazin, Vincent Frochot, Michel Daudon, Felix Renaudin, Sophie Vandermeersch, Amélie E. Coudert, Hang-Korng Ea, Jean-Philippe Haymann, Emmanuel Letavernier, Ellie Tang, Camille Saint-Jacques, Elise Bouderlique, Joëlle Perez, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 0303 health sciences, business.industry, 030232 urology & nephrology, Inflammation, Building and Construction, medicine.disease, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Immunology, medicine, Electrical and Electronic Engineering, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, 2,8-Dihydroxyadenine
Abstract: International audience
Published: 2021

39. Medullary sponge kidney: what kind of stones?

Author: Vincent Frochot, Michel Daudon, Jean-Philippe Haymann, Emmanuel Letavernier, Dominique Bazin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Chimie-Physique (LCP), Université de Cocody, Bazin, Dominique, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, business.industry, 030232 urology & nephrology, Building and Construction, Anatomy, Medullary sponge kidney, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, 030212 general & internal medicine, Electrical and Electronic Engineering, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

40. Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuelle Vidal-Petiot, Martin Flamant, H. Fessi, Christian Jacquot, Jean-Jacques Boffa, Caroline du Halgouet, Pascal Houillier, Marion Vallet, Sandra Wagner, Gérard Maruani, Renaud de la Faille, François Vrtovsnik, Pierre Ronco, Eric Thervet, Eric Daugas, Marine Livrozet, Laurence Nicolet-Barousse, Marie Metzger, Bénédicte Stengel, Nahid Tabibzadeh, Alexandre Karras, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Néphrologie et Hémodialyse [CHU HEGP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, F-CRIN, INICRCT network, Paris, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and NephroTest Study Group: Marine Livrozet, Emmanuel Letavernier, Pierre Ronco, Hafedh Fessi, Emmanuelle Vidal-Petiot, Eric Daugas, Caroline du Halgouet, Renaud de La Faille, Gerard Maruani, Marion Vallet, Laurence Nicolet-Barousse, Alexandre Karras, Christian Jacquot
Subjects: Male, urine concentration ability, 030232 urology & nephrology, Urine osmolality, urologic and male genital diseases, tubular damage, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Prospective Studies, prognostic factor, ComputingMilieux_MISCELLANEOUS, Fasting, Middle Aged, Prognosis, female genital diseases and pregnancy complications, 3. Good health, Survival Rate, Nephrology, Disease Progression, Biomarker (medicine), biomarker, Female, France, medicine.symptom, glomerular filtration rate (GFR), Cohort study, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, CKD progression, Urology, chronic kidney disease (CKD), 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Risk factor, Renal Insufficiency, Chronic, business.industry, Osmolar Concentration, medicine.disease, measured GFR (mGFR), Decreased glomerular filtration rate, end-stage renal disease (ESRD), Albuminuria, GFR decline, business, Biomarkers, Kidney disease
Abstract: International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
Published: 2019

41. 2020 Recommendations from the French Society of Rheumatology for the management of gout: Management of acute flares

Author: Alain Cohen-Solal, Augustin Latourte, Emmanuel Letavernier, Pascal Richette, Frédéric Lioté, Jacques Grichy, Sébastien Ottaviani, Thomas Bardin, Tristan Pascart, Laurence Coblentz-Baumann, Guy Vandecandelaere, Hang-Korng Ea, Gérard Chalès, René-Marc Flipo, Pierre Sigwalt, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Université de Lille, CHU Lille, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: Nephrology, medicine.medical_specialty, Gout, NSAIDs, [SDV]Life Sciences [q-bio], Gout Suppressants, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Corticosteroids, IL-1 inhibitors, 030212 general & internal medicine, Colchicine poisoning, Intensive care medicine, Contraindication, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Drug interaction, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Gout flare, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business, Colchicine, Patient education, Kidney disease
Abstract: Objective To develop French Society of Rheumatology-endorsed recommendations for the management of gout flares. Methods These evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and 2 Delphi rounds to finalize them. Results A set of 4 overarching principles and 4 recommendations was elaborated. The overarching principles emphasize the importance of patient education, including the need to auto-medicate for gout flares as early as possible, if possible within the first 12 h after the onset, according to a pre-defined treatment. Patients must know that gout is a chronic disease, often requiring urate-lowering therapy in addition to flare treatment. Comorbidities and the risk of drug interaction should be screened carefully in every patient as they may contraindicate some anti-inflammatory treatments. Colchicine must be early prescribed at the following dosage: 1 mg then 0.5 mg one hour later, followed by 0.5 mg , 2 to 3 times/day over the next days. In case of diarrhea, which is the first symptom of colchicine poisoning, dosage must be reduced. Colchicine dosage must also be reduced in patients with chronic kidney disease or taking drugs, which interfere with its metabolism. Other first-line treatment options are systemic/intra-articular corticosteroids, or non-steroidal anti-inflammatory agents (NSAIDs). IL-1 inhibitors can be considered as a second-line option in case of failure, intolerance or contraindication to colchicine, corticosteroids and NSAIDs. They are contraindicated in cases of infection and neutrophil blood count should be monitored. Conclusion These recommendations aim to provide strategies for the safe use of anti-inflammatory agents, in order to improve the management of gout flares.
Published: 2020

42. 2020 recommendations from the French Society of Rheumatology for the management of gout: Urate-lowering therapy

Author: Jacques Grichy, Gérard Chalès, Guy Vandecandelaere, Frédéric Lioté, Thomas Bardin, Tristan Pascart, Alain Cohen-Solal, Pierre Sigwalt, Hang-Korng Ea, Pascal Richette, René-Marc Flipo, Laurence Coblentz-Baumann, Emmanuel Letavernier, Sébastien Ottaviani, Augustin Latourte, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Université de Lille, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Université Paris Cité (UPCité), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Chercheur indépendant, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, and CCSD, Accord Elsevier
Subjects: Nephrology, medicine.medical_specialty, Gout, Allopurinol, [SDV]Life Sciences [q-bio], Renal function, Urate lowering therapy, Gout Suppressants, Education, 03 medical and health sciences, 0302 clinical medicine, Febuxostat, Rheumatology, Internal medicine, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, 030203 arthritis & rheumatology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Prophylaxis, medicine.disease, Uric Acid, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, France, business, Kidney disease, Patient education, medicine.drug
Abstract: Objective To develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT). Methods Evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them. Results A set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300 μmol/l (50 mg/l) in all gout patients or at least below 360 μmol/l (60 ml/l) when the 300 μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60 ml/min/1.73 m2, first-line ULT is allopurinol; in those with eGFR between 30 and 60 ml/min/1.73 m2, allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30 ml/min/1.73 m2, allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed. Conclusion These recommendations aim to provide simple and clear guidance for the management of ULT in France.
Published: 2020

43. Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function

Author: Tilman B. Drüeke, Marie Essig, Lynda Cheddani, Ziad A. Massy, Jean Philippe Haymann, Jean-Jacques Boffa, Michel Delahousse, Emmanuel Letavernier, Sophie Liabeuf, Nahid Tabibzadeh, Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], and Gestionnaire, Hal Sorbonne Université
Subjects: cardiovascular risk, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, kidney transplantation, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, AcademicSubjects/MED00340, Pulse wave velocity, Kidney transplantation, 2. Zero hunger, Transplantation, business.industry, Odds ratio, Original Articles, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], carotid-femoral pulse wave velocity (CF-PWV), Nephrology, Arterial stiffness, Cardiology, business, Body mass index, chronic kidney disease, Kidney disease
Abstract: Background Chronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate–matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid–femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR). Methods We analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s). Results At 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P Conclusions Aortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se.
Published: 2020

44. [Crystalline pathologies in the human body: first steps of pathogenesis]

Author: Vincent Frochot, Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, Dominique Bazin, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 030213 general clinical medicine, Pathology, medicine.medical_specialty, Vascular Calcifications, Population, Lithiasis, Pathogenesis, 03 medical and health sciences, Ectopic calcification, Kidney Calculi, 0302 clinical medicine, Urolithiasis, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Humans, education, Vascular Calcification, Process (anatomy), ComputingMilieux_MISCELLANEOUS, education.field_of_study, biology, business.industry, Calcinosis, General Medicine, medicine.disease, 3. Good health, biology.protein, business, Crystallization, Elastin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The prevalence of crystalline pathologies including urolithiasis, gallstones, vascular calcifications and crystalline arthritis, is very high in the general population beyond 60 years old. Characterization of microcrystals in tissue at the micrometer and at the nanometer scale through physico-chemical techniques constitutes a new opportunity for the physician to decipher the early stage of the pathogenesis of these biological entities. In this review, such description indicates a wide variety of the chemical process associated to the nucleation process directly from supersaturated solution or from organic support such as DNA or elastin. We will also discuss the case of vesicles which play a major role in the case of ectopic calcification situated in kidney tissue, namely the Randall's plaque. All this research focused on the very first steps of the genesis of pathological calcifications constitute a major step to develop specific therapy able to avoid the formation of these abnormal deposits in tissues. As already underlined, crystals may be the consequence of various pathologies, but they are also involved in the dysfunction of the tissues.
Published: 2020

45. The Case | Fluctuating serum creatinine and crystals in urine

Author: Marine Livrozet, Michel Daudon, Dominique Bazin, Vincent Frochot, Jeremy Zaworski, Jean-François Benoist, Jean-Jacques Boffa, Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuel Esteve, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 0303 health sciences, Creatinine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Urine, Body Fluids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Nephrology, Heterocyclic Compounds, medicine, [CHIM]Chemical Sciences, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2020

46. Steroids: A Therapeutic Option for COVID-19 Pneumonia Patients With ESRD?

Author: Laurence Nicolet, Karine Dahan, Camille Petit-Hoang, Charles Verney, Martin Viguier, Camille Saint-Jaques, Marion Delafosse, Hélène François, Emmanuel Letavernier, and Julie Peltier
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Pneumonia, Coronavirus disease 2019 (COVID-19), business.industry, Nephrology, Internal medicine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, business, medicine.disease, Article
Published: 2020

47. Stiripentol identifies a therapeutic target to reduce oxaluria

Author: Michel Daudon and Emmanuel Letavernier
Subjects: 030232 urology & nephrology, Calcium oxalate, 030204 cardiovascular system & hematology, Pharmacology, Oxalate, Nephropathy, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oral administration, Lactate dehydrogenase, Internal Medicine, Stiripentol, medicine, Humans, Hyperoxaluria, L-Lactate Dehydrogenase, Oxalic Acid, Dioxolanes, medicine.disease, chemistry, Ethylene glycol poisoning, Nephrology, Hyperoxaluria, Primary, medicine.drug
Abstract: Purpose of review Oxalate is a metabolic end-product promoting the formation of calcium oxalate crystals in urine. Massive urine oxalate excretion occurs in genetic diseases, mainly primary hyperoxaluria type I and II, threatening renal function. Ethylene glycol poisoning may induce the precipitation of calcium oxalate crystals in renal tubules, leading to acute renal failure. In both cases, oxalate results from glyoxylate transformation to oxalate in the liver, by lactate dehydrogenase (LDH) enzymes, especially the LDH-5 isoenzyme. The purpose of the review is to highlight LDH as a potential therapeutic target according to recent publications. Recent findings Genetic therapy targeting LDH metabolism decreases urine oxalate excretion in rodents. Stiripentol is an antiepileptic drug that has been shown recently to inhibit neuronal LDH-5 isoenzyme. Stiripentol was hypothesized to reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol oral administration decreases urine oxalate excretion in rats and protects renal function and renal tissue against ethylene glycol intoxication and chronic calcium oxalate crystalline nephropathy. Summary The use of stiripentol in-vitro and in-vivo highlights that targeting hepatic LDH by pharmacological or genetic tools may decrease oxalate synthesis, deserving clinical studies.
Published: 2020

48. Amoxicillin-induced crystal nephropathy: A nationwide French pharmacovigilance databases study

Author: Joëlle Michot, Nicolas Mongardon, Dominique Vodovar, Marie Zenut, Thierry Trenque, Christine Le Beller, Emmanuel Letavernier, Laure Thomas, Hôpital Henri Mondor, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and VODOVAR, Dominique
Subjects: MESH: Pharmacovigilance, [SDV]Life Sciences [q-bio], medicine.medical_treatment, adverse drug reaction, MESH: Amoxicillin-Potassium Clavulanate Combination, computer.software_genre, Amoxicillin-Potassium Clavulanate Combination, 030226 pharmacology & pharmacy, Nephropathy, law.invention, 03 medical and health sciences, Surgical prophylaxis, Pharmacovigilance, 0302 clinical medicine, law, crystals, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Renal replacement therapy, Retrospective Studies, Pharmacology, MESH: Humans, Database, business.industry, Incidence (epidemiology), Amoxicillin, MESH: Retrospective Studies, Original Articles, MESH: Amoxicillin, medicine.disease, Intensive care unit, MESH: France, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, acute kidney injury, [SDV.TOX]Life Sciences [q-bio]/Toxicology, France, business, renal replacement therapy, computer, Adverse drug reaction, medicine.drug
Abstract: International audience; Aims: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is a rarely reported adverse drug reaction (ADR) but its increase has been recently reported in the Paris area. Our aim was to investigate the incidence, characteristics and outcome of AICN in France.Methods: Retrospective analysis of all AICN cases reported to the French National Pharmacovigilance Database and the Marketing Authorization Holders Pharmacovigilance Database. AICN notification rate was compared to intravenous AMX and AMX-clavulanate sales.Results: In total, 101 AICN cases were included. Intravenous AMX/AMX-clavulanate was prescribed as surgical prophylaxis (32 surgical patients) or to treat infection (69 medical patients). AKI KDIGO stage 3 was observed in 70 patients and 24/70 patients required renal replacement therapy and/or intensive care unit admission. The annual notification rate of AICN was increased by a factor of 13 since 2010 (6 [0;7] and 77 [24;111] cases per 100 000 patient-years of exposure, before and after 2010 respectively; P < .001). In surgical patients, the increase in AICN has been reported since 2010 and was mainly related to inadequate AMX administration. In medical patients, the increase in AICN was observed since 2014. After 2014, medical patients were older (67 [42;77] vs 74 years [64;84] respectively; P < .05) and were treated more frequently for endocarditis (0/20 vs 15/49 respectively; P < .01). A contributing factor was observed or suspected in 62 patients.Conclusion: AICN is a severe ADR that dramatically increased in France since 2010. Assessment of AICN contributing factors and AMX drug monitoring in patients receiving high dose of AMX could reduce the risk of AICN.
Published: 2020

49. Pyrophosphate therapy prevents trauma-induced calcification in the mouse model of neurogenic heterotopic ossification

Author: András Váradi, Eszter Kozák, Zoltán Jakus, Nikolett Hegedűs, Natália Tőkési, Kitti Ajtay, Krisztina Fülöp, Emmanuel Letavernier, Balint Kiraly, Jeremy Zaworski, Viola Pomozi, Krisztián Szigeti, Dóra Dedinszki, Hungarian Academy of Sciences (MTA), Semmelweis University [Budapest], Institute of Experimental Medicine [Budapest] (KOKI), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Adrenergic Antagonists, Pathology, medicine.medical_specialty, Epinephrine, [SDV]Life Sciences [q-bio], Central nervous system, Endogeny, Cardiotoxins, Pyrophosphate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Brain Injuries, Traumatic, medicine, Animals, Effective treatment, preclinical studies, Muscle, Skeletal, Vascular Calcification, Pathological, intervention, bone‐brain‐nervous system interactions, business.industry, Ossification, Heterotopic, Original Articles, X-Ray Microtomography, Cell Biology, medicine.disease, Polytrauma, animal models, Receptors, Adrenergic, Diphosphates, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, chemistry, 030220 oncology & carcinogenesis, Neurogenic heterotopic ossification, disorders of calcium/phosphate metabolism, Molecular Medicine, Original Article, Female, business, Calcification
Abstract: International audience; Trauma‐induced calcification is the pathological consequence of complex injuries which often affect the central nervous system and other parts of the body simultaneously. We demonstrated by an animal model recapitulating the calcification of the above condition that adrenaline transmits the stress signal of brain injury to the calcifying tissues. We have also found that although the level of plasma pyrophosphate, the endogenous inhibitor of calcification, was normal in calcifying animals, it could not counteract the acute calcification. However, externally added pyrophosphate inhibited calcification even when it was administered after the complex injuries. Our finding suggests a potentially powerful clinical intervention of calcification triggered by polytrauma injuries which has no effective treatment.
Published: 2020

50. Pseudoxanthoma Elasticum, Kidney Stones and Pyrophosphate: From a Rare Disease to Urolithiasis and Vascular Calcifications

Author: Emmanuel Letavernier, Elise Bouderlique, Jeremy Zaworski, Ludovic Martin, Michel Daudon, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, pyrophosphate, Pathology, medicine.medical_specialty, kidney, Calcification inhibitor, 030232 urology & nephrology, ABCC6, Review, Gene mutation, GPI-Linked Proteins, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Kidney Calculi, 0302 clinical medicine, Rare Diseases, Urolithiasis, Medicine, Humans, Physical and Theoretical Chemistry, Pseudoxanthoma Elasticum, Vascular Calcification, Molecular Biology, 5'-Nucleotidase, Spectroscopy, Randall’s plaque, biology, business.industry, Organic Chemistry, General Medicine, medicine.disease, Pseudoxanthoma elasticum, 3. Good health, Computer Science Applications, Diphosphates, 030104 developmental biology, Randall's plaque, Mutation, biology.protein, Kidney stones, Nephrocalcinosis, Multidrug Resistance-Associated Proteins, business, Kidney disease, Rare disease
Abstract: International audience; Pseudoxanthoma elasticum is a rare disease mainly due to ABCC6 gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in skin, cardiovascular and retinal calcifications. It has been recently described that pyrophosphate (a calcification inhibitor) deficiency could be the main cause of ectopic calcifications in this disease and in other genetic disorders associated to mutations of ENPP1 or CD73. Patients affected by Pseudoxanthoma Elasticum seem also prone to develop kidney stones originating from papillary calcifications named Randall's plaque, and to a lesser extent may be affected by nephrocalcinosis. In this narrative review, we summarize some recent discoveries relative to the pathophysiology of this mendelian disease responsible for both cardiovascular and renal papillary calcifications, and we discuss the potential implications of pyrophosphate deficiency as a promoter of vascular calcifications in kidney stone formers and in patients affected by chronic kidney disease.
Published: 2019

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