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In France, no consensus document on the management of persistent hyperkalaemia is currently available. Variability in clinical practices has been observed.A consensus statement on the definition and the management of persistent hyperkalaemia was developed by a Delphi panel of French nephrologists between December 2019 (26 voting participants among 40 invited panellists in first round) and June 2020 (20 voting participants among 26 panellists in second round).Persisting hyperkalaemia not controlled with current treatment strategies may be defined as the occurrence of two or more hyperkalaemia episodes within a year despite the administration of cation-exchange resins or loop diuretics during the same year. Some patient characteristics (diabetes, chronic kidney disease from stage 3B to stage 5 without dialysis, chronic heart failure) are associated with an increased risk of developing persistent hyperkalaemia. There is a medical need for the management of persistent hyperkalaemia in patients treated with renin-angiotensin-aldosterone system inhibitors that is not met by current treatment strategies (including available cation-exchange resins).The panel expressed a need for new treatment strategies validated by clinical trials.

International audience

Since a couple of years, a new paradigm of care has taken place where the patient plays a major role in the choice of his treatment. Patient information in a context where the doctor-patient relationship has drastically changed and where knowledge is continuously growing, is a challenge for the nephrologist. For the patient who decides to undergo home dialysis, numerous questions arise during the decision-making process. How should treatment alternatives be discussed with the patient? What are the current data available on the different methods? As comfort, quality of life and level of autonomy often drive the choice of care management, home dialysis can be promoted more with appropriate assistance from both the nephrologist and the healthcare team. Cet article fait partie du numéro supplément Innovations en Néphrologie réalisé avec le soutien institutionnel de Vifor Fresenius Medical Care Renal Pharma.

Chronic kidney disease causes hyperphosphatemia, which is associated with increased cardiovascular risk and mortality. In patients with end-stage renal disease, haemodialysis allows the control of hyperphosphatemia. During a 4-h haemodialysis session, between 600 and 700mg of phosphate are extracted from the plasma, whereas the latter contains only 90mg of inorganic phosphate. The precise origin of phosphates remains unknown. The modelling of phosphorus transfers allows to predict the outcome after changes in dialysis prescription (duration, frequency) with simple two-compartment models and to describe the transfers between the different body compartments with more complex models. Work using

Thrombotic microangiopathy is a rare but severe complication of treatment with gemcitabine. Its prevalence increases because gemcitabine's indications are growing. We report four cases, which presented with common clinical and biological manifestations, i.e. high blood pressure, proteinuria and increasing plasmatic creatinine level. However, severity was not similar, hemodialysis was inconstant. There is no consensus on treatment for this condition. Stopping gemcitabine is essential. Treatment was dispensed considering the severity of the presentation: plasma exchange therapy of variable outcome, and eculizumab, which was efficient when used. It's important to note that this syndrome includes common and frequent signs in patients receiving chemotherapies. But they must encourage the research of most specific signs, such as hypertension, mechanic hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic microangiopathy as early as possible to treat it precociously, and to prevent additional gemcitabine injections.

Kidney dysfunction during congestive heart failure, although frequent, is often neglected. Yet, it represents a life-threatening condition, oven when the kidney dysfunction is moderate. The initial approach involvus strict application of recommendations, cardiologic and nephrologic joined management and close follow-up involving patient's general practitioner. Cases of true diuretics resistance are infrequent and late. Yet, it represents a significant turning point. Mortality is high, with a major individual unpredictability. A multidisciplinary approach is needed, which has to take into account patient's preferences. Several treatments may be discussed and are sometimes joined: cardiac transplantation, water and salt extraction (using ultrafiltration, hemodialysis or peritoneal dialysis), vasoconstrictive drugs, ventricular assistance devices and palliative care. Water and salt extraction techniques seem to space out hospitalizations and to provide symptomatic relief even though no benefit on patient survival has been demonstrated to date. The need for randomized clinical trials is mandatory.

Endovascular revascularization as treatment of atherosclerotic renal-artery stenosis (aRAS) is controversial since 3 large and multicentric randomised trials (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous transluminal renal-artery stenting (PTRAS) over medical treatment only (MT). However, considering the multiple bias of these trials, among which questionable inclusion criterias, these results must be extrapolated in clinical practice with caution. New pathophysiological data have been helping to understand why restoring blood flow does not necessarily lead to kidney function improvement. Today, the diagnostic approach must in one hand confirm the artery stenosis and on the other hand assess its severity and impact on the kidney. Therapeutic options still lie on the American guidelines published in 2006, since no study data can be reasonably used in everyday practice. However, particular sub-groups of patients who could benefit from revascularisation have been identified through recent cohort studies. Further prospective studies are needed in order to confirm the superiority of PTRAS in these populations. Meanwhile, multidisciplinary approach should be promoted, in order to provide the best treatment for each patient.

National audience; Introduction Depuis quelques années, les « migrants sanitaires » semblent de plus en plus nombreux en dialyse en France et leurs conditions sociales sont souvent précaires. Aucune étude ne s’est cependant jusqu’à maintenant intéressée à leur statut social qui pourtant peut conditionner de façon importante leur prise en charge médicale. Ces patients sont le plus souvent pris en charge dans des centres publics au moment de leur arrivée en France. Patients et méthodes Les médecins et les assistants sociaux de 4 centres de dialyse publics (2 à l’Est et 2 à l’Ouest de la France) ont recueilli pour les années 2013 et 2014 le nombre et les données démographiques et sociales des patients « migrants » incidents dans leur centre. Résultats On retrouve 34 patients migrants incidents en dialyse en 2013 et 2014 avec un gradient Est-Ouest (maxi 15 % des incidents 2013 dans un centre de l’Est et mini 0 % en 2013 dans un centre de l’ouest) : 24 hommes, âge moyen 44,6 ± 13,9 ans, 19/34 au moins dialysaient avant leur arrivée en France. Les pays d’origine sont : Kosovo (6), Arménie (4), Géorgie (4), Algérie (3), Cameroun (3), Tadjikistan (2), Angola (2), Russie (2), Bosnie (1), Serbie (1), Biélorussie (1), Madagascar (1), Somalie (1), Sri Lanka (1), Congo (1), et Mongolie (1). Un grand nombre de patients ont initialement un statut « Demandeurs d’Asile (DA) » ou « Étrangers Malades (EM) ». La couverture sociale est l’AME, les « soins urgents » ou la CMU après 3 mois. La plupart des patients (26/34) ne maîtrisent pas le français (besoin d’interprète pour discuter avec l’assistant social et les médecins). Une partie (9/34) habite chez des compatriotes, 9 doivent recourir au 115 et les autres vivent dans des foyers. Discussion Sur ces quatre centres, il existe de nombreux patients souvent déjà dialysés dans leur pays d’origine, venant notamment des pays de l’Est avec un fort gradient Est-Ouest en France. Leur situation sociale est précaire, rendant leur prise en charge en dialyse plus compliquée et grevant probablement leur survie. Conclusion Cette étude pilote volontairement axée sur des hôpitaux publics montre que la collaboration entre les néphrologues et les services sociaux permet de mieux préciser la situation des patients migrants dialysés

Dialysis patients frequently have anxiety and sleeping disorders and that explains a benzodiazepine treatment. A significant proportion of dialysis patients are long-term users even though it is not recommended to take benzodiazepine for more than 3 months. Risks of such a use are well identified. Nephrologists frequently have to prescribe benzodiazepines. This prescription is complex and there are few studies regarding the factors of benzodiazepine use among this population.To determine the prevalence and the factors related to a long-term benzodiazepine use by dialysis patients. To determine the prevalence and the motivation of patients to stop taking medication among the long-term users who got information about the risk of such a use.The study includes 91 dialysis chronic patients. Their characteristics were collected from medical records and interviews with the patients.The average age of patients is 65,8 years. In all, 50.5% take benzodiazepines. Among benzodiazepine users, the prevalence of long-term use is 78.3%. Long-term benzodiazepine users (a) are older, (b) less active, (c) frequently diabetic, (d) depressive, (e) unable to walk, (f) less often registered on the kidney transplant waiting list, and (g) had less kidney transplant previously. Benzodiazepine doses of long-term users were higher than the doses of short-term users. Moreover, 60% of patients who are chronic users want to take action and stop the treatment. Observation of side effects, impression of ineffectiveness and fear of addiction are the most identified motivation to stop treatment.The prevalence of benzodiazepine chronic use by dialysis patients is high. Giving information to the patient about the use of these molecules seems to have a positive impact on the decision to stop.

Pregnancy in patients presenting end-stage renal disease is rare and there are currently no recommendations for the management of these patients. In hemodialysis patients, reduced fertility and medical reluctance limit the frequency of pregnancies. Although the prognosis has significantly improved, a significant risk for unfavorable maternal (pre-eclampsia, eclampsia) and fetal (pre-term birth, intrauterine growth restriction, still death) outcome still remains. Increasing dialysis dose with the initiation of daily dialysis sessions, early adaptation of medications to limit teratogenicity and management of chronic kidney disease complications (anemia, hypertension) are required. A tight coordination between nephrologists and obstetricians remains the central pillar of the care. In peritoneal dialysis, pregnancy is also possible with modification of the exchange protocol and reducing volumes.

There are few epidemiologic data on Chronic Kidney Disease management before replacement therapy. The two objectives of the PREPARE study were (1) to describe the characteristics of these patients and accordance to clinical practice guidelines (2) to study nephrologists preference for renal replacement therapy in case of progression to end stage renal disease. PREPARE is a non-interventional cross-sectional study. All the French nephrologists had been solicited to collect information about CKD outpatients not on dialysis, not transplanted, with glomerular filtration rate lower than 60mL/min/1,73m(2), followed on any day between 23 and 27 November 2009. Three hundred and eight investigators included 2089 patients, 59% of them were male, they were on average 69 years old, 15, 37 and 48% had respectively a CKD stage V, stage IV and stage III, the nephropathy was the most often (43%) vascular. The most frequently reported cardiovascular risk factors were hypertension (88%), hypercholesterolemia (53%), diabetes (37%). The average time between diagnosis of nephropathy and the first nephrology consultation was too long 1,5 years. The implementation measures of nephroprotection and treatment of complications of CKD were generally satisfactory. However, preparation for replacement therapy was often too late, haemodialysis was more likely scheduled instead of peritoneal dialysis and without preparation for renal transplantation. PREPARE can therefore highlight the qualities of the current management of CKD by nephrologists in France. Nevertheless, PREPARE also shows weaknesses in preparation for replacement therapy. One can suggest that they could be reduced by systematic access of patients with risk of progression to stage V, as soon as the stage IV, to structured multidisciplinary care.

Many quantitative clinical, biological and radiological parameters are useful in medicine for guiding diagnosis and therapy. The nephrologists use such parameters on a daily basis, particularly to assess renal function. In order to use the measurement methods of these parameters in clinical practice, it is mandatory to establish the agreement of the values provided, comparatively to the value obtained by using the reference measurement method of this parameter. This review details the methodology for the validation of methods for estimating quantitative parameters.

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered.

Blood Oxygen Level-Dependent (BOLD) MRI signal is a new method of renal functional imaging which allows renal cortical and medullary oxygen contents measurement in a noninvasive way and without injection of potentially nephrotoxic contrast product. Several clinical and experimental studies showed its potential interest in measuring renal oxygen content and its variation during different renal injuries, allowing new progress in the comprehension of the pathophysiology of several nephropathies.

Chronic renal disease is a state of microinflammation and insulin resistance. They both impact on the patient's outcome with an increased cardiovascular morbi-mortality and malnutrition. Current evidence suggests that there is a link between these two abnormal conditions. Recent data show a multiple organ regulatory pathway with a key role of bone, adipose tissue, immune system and central nervous system in energy balance control and glucose homeostasis. Thus, in searching for effective therapies, we should use an integrated approach aimed at modifying integrated outcomes rather than targeting single molecules.

Nutritional guidelines are scarce for patients receiving maintenance hemodialysis. In this review, we address the recent European guidelines released in 2007. They include diagnosis and follow-up criteria for malnutrition to be performed routinely. They provide new values for protein and energy requirements, based on physical activity. Vitamins and trace elements requirements are proposed. The renutrition therapies are addressed, i.e., oral supplement, enteral and intradialytic parenteral nutrition. Finally, androgens, quotidian dialysis and acidosis treatment are also considered.

Chronic kidney disease is a public health problem in terms of both the number of patients treated with dialysis or transplantation and the cost of renal replacement therapies, and the excess cardiovascular risk associated with it even at earliest stages. The population of people with chronic renal insufficiency (defined by a glomerular filtration rate60 mL/min) and therefore exposed to the risk of progression towards end-stage renal failure and excess cardiovascular risk includes roughly 5% of the general population. There are currently effective treatments to slow the progression of chronic kidney disease, delay or avoid dialysis, and prevent cardiovascular events. These treatments are most effective when begun earliest and when followed by professionals aware of the risk factors and the intermediate efficacy criteria: blood pressure, proteinuria, diet, anemia, etc. (Anaes, 2004). Screening for chronic kidney disease is currently facilitated by the routine estimate of creatinine clearance with Cockcroft's formula at every serum creatinine assay (Anaes, 2002). Nephrologists play an essential role when kidney disease is discovered, for it is they who must recognize diseases related to specific treatments and thus to define the long-term risk prevention strategy. Chronic kidney disease develops over years, during which time the patient will see a variety of different healthcare professionals. The transmission of medical information between them is a prerequisite for the continuity of nephroprotective treatment, the prevention of avoidable causes of aggravation (drugs, contrast products, etc.), and the quality of preparation for substitution treatment and transplantation. Because of late referral to nephrologists and insufficient information, an elevated proportion (about 40%) of patients start dialysis in emergency conditions, which reduces their chance of maintaining their independence and using a home-based dialysis method. The system of health networks should provide responses particularly appropriate to the needs of patients with chronic kidney disease. In particular, these networks promote continued medical education, consistent and thorough patient information, and evaluation of practices (HAS, 2006).

Cardiovascular complications remain the main problem in chronic kidney disease (CKD) but all the reasons of this risk are not fully understood. there is an addition of traditional risk factors and uremia-related ones. Among the latter, the generation of post-translational modifications of HDL could play a role. In this work, we highlighted an excess of carbonylation by 4-HNE onto the protein part of HDL in CKD in a rabbit model of CKD and in hemodialysis and peritoneal dialysis patients. This carbonylation by 4-HNE is responsible for ablunted anti-aggregant properties of HDL mediated by a CD36-dependant pathway. We also showed that the proteome of HDL from non diabetic hemodialysis patients is deeply modified and that there were several post-translational modifications onto the protein cargo of these HDL. The generation of carboxylate-methyl-lysine from non-enzymatic glycation processes was the main modification in our patients. The origin of such glycation could be from a favorable chemical environment but a potential load from hemodialysis fluids should be addressed; Les complications cardiovasculaires restent prépondérantes dans l’insuffisance rénale chronique bien que les causes demeurent assez méconnues. Il existe une addition chez les patients insuffisants rénaux chroniques de facteurs de risque cardiovasculaires classiques et d’autres plus spécifiques à l’insuffisance rénale. Parmi ces derniers, la formation de modifications post-traductionnelles (adduits issus de réactions oxydatives et non-oxydatives) sur les lipoprotéines HDL pourrait jouer un rôle. Dans ce travail nous avons mis en évidence d’une part, un excès de carbonylation par le 4-HNE sur les HDL dans l’IRC sur un modèle animal de lapin et chez le patient hémodialysé ou dialysé péritonéal. Cette carbonylation par le 4-HNE est responsable d’une altération des propriétés anti-agrégantes des HDL et ce par une voie médiée par le récepteur scavenger CD36. Nous avons aussi montré que le protéome des HDL était modifié chez le patient HD et qu’il existait un large éventail d’adduits covalents sur les HDL de patients hémodialysés non-diabétiques. La formation de carboxy-méthyl-lysine issue de la glycation était la principale modification post-traductionnelle observée chez les patients HD. Cela questionne sur l’origine de cet excès de glycation qui pourrait être dû à un environnement chimique favorable chez les patients mais un apport exogène par les solutés utilisés en hémodialyse est aussi possible

Cardiovascular complications remain the main problem in chronic kidney disease (CKD) but all the reasons of this risk are not fully understood. there is an addition of traditional risk factors and uremia-related ones. Among the latter, the generation of post-translational modifications of HDL could play a role. In this work, we highlighted an excess of carbonylation by 4-HNE onto the protein part of HDL in CKD in a rabbit model of CKD and in hemodialysis and peritoneal dialysis patients. This carbonylation by 4-HNE is responsible for ablunted anti-aggregant properties of HDL mediated by a CD36-dependant pathway. We also showed that the proteome of HDL from non diabetic hemodialysis patients is deeply modified and that there were several post-translational modifications onto the protein cargo of these HDL. The generation of carboxylate-methyl-lysine from non-enzymatic glycation processes was the main modification in our patients. The origin of such glycation could be from a favorable chemical environment but a potential load from hemodialysis fluids should be addressed, Les complications cardiovasculaires restent prépondérantes dans l’insuffisance rénale chronique bien que les causes demeurent assez méconnues. Il existe une addition chez les patients insuffisants rénaux chroniques de facteurs de risque cardiovasculaires classiques et d’autres plus spécifiques à l’insuffisance rénale. Parmi ces derniers, la formation de modifications post-traductionnelles (adduits issus de réactions oxydatives et non-oxydatives) sur les lipoprotéines HDL pourrait jouer un rôle. Dans ce travail nous avons mis en évidence d’une part, un excès de carbonylation par le 4-HNE sur les HDL dans l’IRC sur un modèle animal de lapin et chez le patient hémodialysé ou dialysé péritonéal. Cette carbonylation par le 4-HNE est responsable d’une altération des propriétés anti-agrégantes des HDL et ce par une voie médiée par le récepteur scavenger CD36. Nous avons aussi montré que le protéome des HDL était modifié chez le patient HD et qu’il existait un large éventail d’adduits covalents sur les HDL de patients hémodialysés non-diabétiques. La formation de carboxy-méthyl-lysine issue de la glycation était la principale modification post-traductionnelle observée chez les patients HD. Cela questionne sur l’origine de cet excès de glycation qui pourrait être dû à un environnement chimique favorable chez les patients mais un apport exogène par les solutés utilisés en hémodialyse est aussi possible

The increase in the incidence of chronic renal failure worldwide requires improvements in measures to slow its progression to end-stage renal failure. The low-protein diet or the prevention of episodes of ischemia-reperfusion belong to these measures of nephroprotection but their benefit is only incompletely understood. The kidney is one of the most vascularized organs, compared to its weight, the concomitant evaluation of renal perfusion ([15O] H2O), oxidative metabolism ([11C] acetate) and tissue content in oxygen (BOLD-IRM) is fundamental in that these three measures are not linearly correlated. PETMRI, a hybrid device combining the functionalities of PET and MRI, allows a concomitant evaluation of these three parameters in a non-invasive and isolated kidney way which allows to use it in clinical research for the evaluation of the effect of different interventions. Low-protein diets have been shown to slow down the decline in renal function, but the mechanism behind this beneficial effect is not known. We have demonstrated that the AGE (Advanced Glycation End Products) content of a protein load is responsible for the mobilization of the renal functional reserve with an increase in perfusion and oxidative metabolism after a high- AGE high- protein compared to a low- AGE high- protein load. Our results make it possible to question the interest of a low-AGE diet for chronic renal insufficiency beyond a pure protein restriction. The prevention of episodes of ischemia reperfusion is also particularly important in the context of nephroprotection, whereas the revascularization of a stenosis of the renal artery is necessarily accompanied by reperfusion injury. Use of ciclosporin prior to dilation of renal artery stenosis in pre-conditioning reduced renal damage in mice, but this clinical benefit has not been demonstrated in humans. The CICLOSAAR study, which aims to evaluate the benefit of pre-conditioning with ciclosporin before dilation of renal artery stenosis with renal functional parameters (perfusion, oxidative metabolism and tissue oxygen content) is in progress. In a second step and to improve the clinical applicability of these functional imaging techniques, we have shown that acetate, which was previously used as a marker of oxidative metabolism, could also be used as a marker of renal perfusion through the modeling of its uptake by the kidney. In total, PET-MRI is a fundamental tool for the evaluation of renal functional parameters in a non-invasive way in humans. Demonstrating the impact of the AGE content of a protein load on perfusion and renal metabolism should help refine our dietary advice to patients with chronic kidney disease to prevent progression of the disease to end-stage renal failure. The current CicloSAAR study is expected to improve the measures implemented to protect the kidney from reperfusion injury after dilatation of renal artery stenosis. Finally, our results on the strong correlation between acetate and water perfusion data should allow this tracer to be used to obtain perfusion and oxidative metabolism after a single radio tracer injection and reinforce clinical applicability of these techniques, La progression de l'incidence de l'insuffisance rénale chronique dans le monde nécessite d'améliorer les mesures visant à ralentir sa progression et son évolution vers l'insuffisance rénale terminale. Le régime pauvre en protéines ou la prévention des épisodes d'ischémie- reperfusion appartiennent à ces mesures de néphroprotection mais leur bénéfice n'est qu'incomplètement compris. Le rein étant un des organes les plus vascularisé, rapporté à son poids, l'évaluation concomitante de la perfusion rénale ([15O]H2O), du métabolisme oxydatif ([11C]acetate) puis du contenu tissulaire en oxygène (BOLD-IRM) est fondamentale dans la mesure où ces trois mesures ne sont pas corrélées de manière linéaire. La TEP-IRM, appareil hybride combinant les fonctionnalités de la TEP et de l'IRM, permet une évaluation concomitante de ces trois paramètres de manière non invasive et sur rein isolé ce qui permet de l'utiliser en recherche clinique pour l'évaluation de l'effet de différentes interventions. Les régimes pauvres en protéines ont démontré qu'ils permettaient un ralentissement du déclin de la fonction rénale mais le mécanisme à l'origine de cet effet bénéfique n'est pas connu. Nous avons démontré que le contenu en AGE (Advanced Glycation End Products ou protéines modifiées) d'une charge protéique était responsable de la mobilisation de la réserve fonctionnelle rénale avec une augmentation de la perfusion et du métabolisme oxydatif plus importants après une charge protéique riche en AGE par rapport à une charge protéique pauvre en AGE. Nos résultats permettent de s'interroger sur l'intérêt d'une alimentation pauvre en AGE pour les insuffisants rénaux chroniques au-delà d'une restriction protéique pure. La prévention des épisodes d'ischémie- reperfusion est également particulièrement importante dans le cadre de la néphroprotection alors que la revascularisation d'une sténose de l'artère rénale s'accompagne obligatoirement de lésions de reperfusion. L'utilisation de la ciclosporine avant la dilatation d'une sténose de l'artère rénale dans le cadre d'un pré conditionnement a permis de réduire les lésions rénales chez la souris mais ce bénéfice clinique n'a pas été démontré chez l'homme. L'étude CICLOSAAR qui a pour but d'évaluer le bénéfice d'un pré conditionnement par la ciclosporine A avant dilatation d'une sténose de l'artère rénale sur des paramètres fonctionnels rénaux (perfusion, métabolisme oxydatif et contenu tissulaire en oxygène) est en cours. Dans un second temps et afin d'améliorer l'applicabilité clinique de ces techniques d'imagerie fonctionnelle, nous avons démontré que l'acétate, qui était jusque-là utilisé comme un marqueur de métabolisme oxydatif, pouvait également être utilisé comme un marqueur de perfusion rénale grâce à la modélisation de son uptake par le rein. Au total, la TEP- IRM est un outil fondamental pour l'évaluation des paramètres fonctionnels rénaux de manière non invasive chez l'humain. La mise en évidence de l'impact du contenu en AGE sur la perfusion et le métabolisme rénal devrait permettre d'affiner nos conseils diététiques aux insuffisants rénaux pour prévenir la progression de la maladie vers l'insuffisance rénale terminale. L'étude CicloSAAR actuellement en cours devrait permettre d'améliorer les mesures mises en oeuvre pour protéger le rein des lésions de reperfusion après dilatation d'une sténose de l'artère rénale. Enfin, nos résultats sur la forte corrélation entre les données de perfusion en acétate et en eau devraient permettre d'utiliser ce traceur pour obtenir la perfusion et le métabolisme oxydatif à l'issue d'une seule injection de radio-traceur et renforcer l'applicabilité clinique de ces techniques

Ischemia-reperfusion (IR) is a situation encountered in transplantation or during aortic surgery, which can result in renal damages, requiring sometimes transient or definitive dialysis. Mitochondria play a crucial role in the pathophysiology of IR causing cell death. Previous studies of cardiac IR highlighted the role of mitochondrial permeability transition pore (mPTP). Cyclosporin A (CsA) has been proposed as a treatment to protect the kidney from IR by the delay of the opening of the mPTP. However, CsA has acute renal hemodynamic effects and a long-term toxicity, requiring an experimental validation of its protection in the renal IR. In this work, we developed a mouse model of renal IR. In a first study, we showed that the post-conditioning with CsA and ischemic postconditioning improve renal function with a delay of the opening of the mPTP. In a second study, we showed that a high dose of CsA injected just before the ischemia improves renal function and leads to the delay of the opening of mPTP mediated by an increase of HSP70. Our results open new perspectives in renal protection, especially for reducing episodes of acute renal failure in aortic surgery or in renal transplantation, L'ischémie-reperfusion (IR) rénale entraîne des lésions de nécrose tubulaire aigue, nécessitant parfois une épuration extra rénale transitoire voir définitive. La mitochondrie joue un rôle important dans la physiopathologie de ces lésions d'IR en entrainant la mort cellulaire. L'étude de l'IR dans la cellule cardiaque a permis de mettre en évidence le rôle central du pore de transition de perméabilité mitochondriale (mPTP) dans le déclenchement de cette mort cellulaire. La ciclosporine (CsA) a été proposée comme thérapeutique pour protéger la cellule des lésions d'IR en retardant l'ouverture de ce mPTP. Cependant la CsA a des effets rénaux vasoconstricteurs aigus, nécessitant une validation expérimentale de sa protection dans l'IR rénale. Au cours de ce travail de thèse, nous avons mis au point un modèle murin d'IR rénale. Ensuite nous avons montré que le post-conditionnement à la CsA, ainsi que le post-conditionnement ischémique, permettent d'améliorer la fonction rénale avec un retard à l'ouverture du mPTP. Dans un deuxième travail, nous montrons que le pré conditionnement à la CsA est dose et temps dépendant, et médié en partie par l'augmentation d'expression d'une protéine chaperonne, l'Heat Shock Protéine 70 (HSP70). L'injection en bolus de CsA permet également d'améliorer la fonction rénale dans ce modèle d'IR avec un retard à l'ouverture du mPTP. Nos résultats ouvrent de nouvelles perspectives dans la protection rénale, notamment dans la réduction des épisodes d'insuffisance rénale aigue après chirurgie aortique ou en transplantation rénale

Ischemia-reperfusion (IR) is a situation encountered in transplantation or during aortic surgery, which can result in renal damages, requiring sometimes transient or definitive dialysis. Mitochondria play a crucial role in the pathophysiology of IR causing cell death. Previous studies of cardiac IR highlighted the role of mitochondrial permeability transition pore (mPTP). Cyclosporin A (CsA) has been proposed as a treatment to protect the kidney from IR by the delay of the opening of the mPTP. However, CsA has acute renal hemodynamic effects and a long-term toxicity, requiring an experimental validation of its protection in the renal IR. In this work, we developed a mouse model of renal IR. In a first study, we showed that the post-conditioning with CsA and ischemic postconditioning improve renal function with a delay of the opening of the mPTP. In a second study, we showed that a high dose of CsA injected just before the ischemia improves renal function and leads to the delay of the opening of mPTP mediated by an increase of HSP70. Our results open new perspectives in renal protection, especially for reducing episodes of acute renal failure in aortic surgery or in renal transplantation, L'ischémie-reperfusion (IR) rénale entraîne des lésions de nécrose tubulaire aigue, nécessitant parfois une épuration extra rénale transitoire voir définitive. La mitochondrie joue un rôle important dans la physiopathologie de ces lésions d'IR en entrainant la mort cellulaire. L'étude de l'IR dans la cellule cardiaque a permis de mettre en évidence le rôle central du pore de transition de perméabilité mitochondriale (mPTP) dans le déclenchement de cette mort cellulaire. La ciclosporine (CsA) a été proposée comme thérapeutique pour protéger la cellule des lésions d'IR en retardant l'ouverture de ce mPTP. Cependant la CsA a des effets rénaux vasoconstricteurs aigus, nécessitant une validation expérimentale de sa protection dans l'IR rénale. Au cours de ce travail de thèse, nous avons mis au point un modèle murin d'IR rénale. Ensuite nous avons montré que le post-conditionnement à la CsA, ainsi que le post-conditionnement ischémique, permettent d'améliorer la fonction rénale avec un retard à l'ouverture du mPTP. Dans un deuxième travail, nous montrons que le pré conditionnement à la CsA est dose et temps dépendant, et médié en partie par l'augmentation d'expression d'une protéine chaperonne, l'Heat Shock Protéine 70 (HSP70). L'injection en bolus de CsA permet également d'améliorer la fonction rénale dans ce modèle d'IR avec un retard à l'ouverture du mPTP. Nos résultats ouvrent de nouvelles perspectives dans la protection rénale, notamment dans la réduction des épisodes d'insuffisance rénale aigue après chirurgie aortique ou en transplantation rénale