186 results on '"De Seigneux S"'
Search Results
2. Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study
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Schreiber, P.W., primary, Laager, M., additional, Boggian, K., additional, Neofytos, D., additional, van Delden, C., additional, Egli, A., additional, Dickenmann, M., additional, Hirzel, C., additional, Manuel, O., additional, Koller, M., additional, Rossi, S., additional, Schmied, B., additional, Gürke, L., additional, Matter, M., additional, Berney, T., additional, de Rougemont, O., additional, Kuster, S.P., additional, Stampf, S., additional, Mueller, N.J., additional, Amico, P., additional, Aubert, J-D., additional, Banz, V., additional, Beckmann, S., additional, Beldi, G., additional, Berger, C., additional, Berishvili, E., additional, Berzigotti, A., additional, Binet, I., additional, Bochud, P-Y., additional, Branca, S., additional, Bucher, H., additional, Catana, E., additional, Cairoli, A., additional, Chalandon, Y., additional, De Geest, S., additional, De Rougemont, O., additional, De Seigneux, S., additional, Dreifuss, J.L., additional, Duchosal, M., additional, Fehr, T., additional, Ferrari-Lacraz, S., additional, Garzoni, C., additional, Golshayan, D., additional, Goossens, N., additional, Halter, F.H.J., additional, Heim, D., additional, Hess, C., additional, Hillinger, S., additional, Hirsch, H.H., additional, Hirt, P., additional, Hofbauer, G., additional, Huynh-Do, U., additional, Immer, F., additional, Laesser, B., additional, Lamoth, F., additional, Lehmann, R., additional, Leichtle, A., additional, Marti, H.P., additional, Martinelli, M., additional, McLin, V., additional, Mellac, K., additional, Merçay, A., additional, Mettler, K., additional, Müller, A., additional, Müller-Arndt, U., additional, Müllhaupt, B., additional, Nägeli, M., additional, Oldani, G., additional, Pascual, M., additional, Passweg, J., additional, Pazeller, R., additional, Posfay-Barbe, K., additional, Rick, J., additional, Rosselet, A., additional, Rothlin, S., additional, Ruschitzka, F., additional, Schachtner, T., additional, Schanz, U., additional, Schaub, S., additional, Scherrer, A., additional, Schnyder, A., additional, Schuurmans, M., additional, Schwab, S., additional, Sengstag, T., additional, Simonetta, F., additional, Steiger, J., additional, Stirnimann, G., additional, Stürzinger, U., additional, Van Delden, C., additional, Venetz, J-P., additional, Villard, J., additional, Vionnet, J., additional, Wick, M., additional, Wilhelm, M., additional, and Yerly, P., additional
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- 2022
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3. Acute and long term mineral metabolism adaptation in living kidney donors: A prospective study
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Ponte, B., Trombetti, A., Hadaya, K., Ernandez, T., Fumeaux, D., Iselin, C., Martin, P.-Y., and de Seigneux, S.
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- 2014
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4. Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology
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Zanchi, A., Jehle, A.W., Lamine, F., Vogt, B., Czerlau, C., Bilz, S., Seeger, H., and de Seigneux, S.
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Humans ,Diabetic Nephropathies/therapy ,Diabetes Mellitus, Type 2/complications ,Diabetes Mellitus, Type 2/drug therapy ,Nephrology ,Blood Glucose/metabolism ,Switzerland ,Disease Progression ,Cardiovascular Diseases/etiology ,Renal Insufficiency, Chronic/complications ,610 Medicine & health ,General Medicine ,610 Medizin und Gesundheit - Abstract
Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease. First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future.
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- 2023
5. Vingt ans de néphrologie à Genève
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Martin, P.Y., De Seigneux, S., and Fakhouri, F.
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Humans ,Nephrology ,General Medicine - Published
- 2022
6. Inhibiteurs du SGLT2 dans les néphropathies diabétiques et non diabétiques [SGLT2 inhibitors in diabetic and non-diabetic nephropathies]
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Scheen, M., Zanchi, A., Martin, P.Y., and De Seigneux, S.
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Diabetes Mellitus, Type 2 ,Diabetic Nephropathies/drug therapy ,Humans ,Hypoglycemic Agents/therapeutic use ,Sodium-Glucose Transporter 2 ,Sodium-Glucose Transporter 2 Inhibitors/therapeutic use - Abstract
SGLT2 inhibitors (SGLT2i) will change the clinical practice of nephrology with their therapeutic cardiorenal and antidiabetic properties. By inhibiting proximal tubular sodium and glucose reabsorption, these new drugs decrease intraglomerular pressures. Over the last 5 years several breakthrough studies have demonstrated the SGLT2i protective effects on outcomes such as cardiovascular mortality, hospital admission for heart failure, sustained decreases in eGFR in patients with diabetic nephropathy and the development of ESKD. With the new DAPA-CKD study revealing protective effects of SGLT2i in CKD patients without diabetes, therapeutic recommendations will now have to evolve towards including these drugs in the chronic management of all most proteinuric CKD patients.
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- 2021
7. Brief dietary protein dilution using carbohydrate rich drink protects from kidney ischemia and reperfusion injuries trough IGF-1
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Emsley, R, primary, Agius, T, additional, Macabrey, D, additional, Faivre, A, additional, Déglise, S, additional, De Seigneux, S, additional, Corpataux, J -M, additional, Allagnat, F, additional, and Longchamp, A, additional
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- 2021
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8. Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure
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Saudan, P, Niederberger, M, De Seigneux, S, Romand, J, Pugin, J, Perneger, T, and Martin, P Y
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- 2006
9. L’IRM de diffusion permet de détecter une augmentation de la fibrose intersitielle avant la baisse de la fonction rénale
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Berchtold, L., primary, Crowe, L.A., additional, Friedli, I., additional, Moll, S., additional, De Perrot, T., additional, Martin, P.Y., additional, Vallée, J.P., additional, and De Seigneux, S., additional
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- 2019
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10. Développement d’un score combinant l’IRM de diffusion à des marqueurs sanguins pour quantifier la fibrose rénale
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Berchtold, L., primary, Friedli, I., additional, Crowe, L.A., additional, Martinez, C., additional, Moll, S., additional, Hadaya, K., additional, De Perrot, T., additional, Martin, P.Y., additional, Vallee, J.P., additional, and De Seigneux, S., additional
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- 2018
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11. NON-DIPPING PHENOMENON MEASURED BY 24H-AMBULATORY BLOOD PRESSURE MONITORING IS A STRONG PREDICTOR OF LEFT VENTRICULAR HYPERTROPHY IN CHRONIC KIDNEY DISEASE
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Jaques, D., primary, Muller, H., additional, Martinez, C., additional, De Seigneux, S., additional, Martin, P., additional, Saudan, P., additional, and Ponte, B., additional
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- 2018
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12. New Magnetic Resonance Imaging Index for Renal Fibrosis Assessment: A Comparison between Diffusion-Weighted Imaging and T1 Mapping with Histological Validation
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Friedli, I., primary, Crowe, L. A., additional, Berchtold, L., additional, Moll, S., additional, Hadaya, K., additional, de Perrot, T., additional, Vesin, C., additional, Martin, P.-Y., additional, de Seigneux, S., additional, and Vallée, J.-P., additional
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- 2016
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13. Management of patients with nephrotic syndrome
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de Seigneux, S. and Martin, Pierre-Yves
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ddc:616 ,Dyslipidemias/etiology ,Angiotensin II Type 1 Receptor Blockers/*therapeutic use ,Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ,Humans ,Hypertension/drug therapy/etiology ,Nephrotic Syndrome/complications/diagnosis/*drug therapy ,Anemia/etiology ,Thromboembolism/etiology ,Edema/etiology - Abstract
Nephrotic syndrome is characterised by proteinuria >3.5 g/24h, oedema, hypoalbuminaemia and hyperlipidaemia. Several glomerular diseases, either primary or secondary, may lead to nephrotic syndrome. Investigations for nephrotic syndrome include immunological and infectious evaluations. Renal biopsy is often mandatory, except in diabetes. Depending on aetiology specific treatment, often with immunosuppressive agents, may be implemented. In any cases nonspecific treatment should be started with ACE inhibitors or ARBs. Urinary protein loss leads to several complications: water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism. Each of these complications must be identified.
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- 2009
14. Increased apical targeting of renal epithelial sodium channel subunits and decreased expression of type 21! i beta-hydroxysteroid
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Kim, S.W., Schou, U.K., Peters, C.D., de Seigneux, S., Kwon, Tae-Hwan, Knepper, Mark A., Jonassen, Thomas E.N., Frokiaer, J., Nielsen, S., Kim, S.W., Schou, U.K., Peters, C.D., de Seigneux, S., Kwon, Tae-Hwan, Knepper, Mark A., Jonassen, Thomas E.N., Frokiaer, J., and Nielsen, S.
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- 2005
15. Neutropénies sévères précoces post transplantation rénale : prédominance des causes médicamenteuses incluant le tacrolimus
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Michelet, P.-R., primary, Ponte, B., additional, Samii, K., additional, de Seigneux, S., additional, Martin, P.-Y., additional, and Hadaya, K., additional
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- 2012
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16. L’invalidation de NOX4 aggrave la fibrose rénale dans l’obstruction urinaire
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Nlandlu Khodo, S., primary, Dizin, E., additional, Martin, P.-Y., additional, Feraille, E., additional, Krause, K.-H., additional, and de Seigneux, S., additional
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- 2012
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17. Suivi spécialisé chez les patients avec maladie rénale chronique stade IIIb-IV : impact sur la survie et les hospitalisations en urgence ?
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Saudan, P., primary, Marangon, N., additional, de Seigneux, S., additional, Ponte, B., additional, Stoermann, C., additional, Martinez, C., additional, and Martin, P.-Y., additional
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- 2012
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18. The risk of acute kidney injury following laparoscopic surgery in a chronic kidney disease patient
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de Seigneux, S., primary, Klopfenstein, C.-E., additional, Iselin, C., additional, and Martin, P.-Y., additional
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- 2011
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19. Rapid and segmental specific dysregulation of AQP2, S256-pAQP2 and renal sodium transporters in rats with LPS-induced endotoxaemia
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Olesen, E. T. B., primary, de Seigneux, S., additional, Wang, G., additional, Lutken, S. C., additional, Frokiaer, J., additional, Kwon, T.-H., additional, and Nielsen, S., additional
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- 2009
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20. Extrarenale Entstehungsmechanismen von Ödemen
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de Seigneux, S, primary, Feraille, E, additional, and Martin, PY, additional
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- 2003
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21. Mécanismes extrarénaux de la formation des oedèmes
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de Seigneux, S, primary, Feraille, E, additional, and Martin, PY, additional
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- 2003
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22. Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study
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de Seigneux Sophie, Ponte Belen, Weiss Lucien, Pugin Jérôme, Romand Jacques, Martin Pierre-Yves, and Saudan Patrick
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Erythropoetin ,NGAL ,Cytokines ,AKI ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Experimentally, erythropoietin (EPO) has nephroprotective as well as immunomodulatory properties when administered after ischemic renal injury. We tested the hypothesis that different doses of recombinant human EPO administered to patients after cardiac surgery would minimize kidney lesions and the systemic inflammatory response, thereby decreasing acute kidney injury (AKI) incidence. Methods In this double-blinded randomized control study, 80 patients admitted to the ICU post-cardiac surgery were randomized by computer to receive intravenously isotonic saline (n = 40) versus α-Epoetin (n = 40): either 40000 IU (n = 20) or 20000 IU (n = 20). The study lasted one year. The primary outcome was the change in urinary NGAL concentration from baseline and 48 h after EPO injection. Creatinine, cystatine C and urinary NGAL levels were measured on the day of randomization and 2–4 days after EPO injection. To assess acute inflammatory response, serum cytokines (IL6 and IL8) were measured at randomization and four days after r-HuEPO injection. Patients and care-takers were blinded for the assignment. Results No patient was excluded after randomization. Patient groups did not differ in terms of age, gender, comorbidities and renal function at randomization. The rate of AKI assessed by AKIN criteria was 22.5% in our population. EPO treatment did not significantly modify the difference in uNGAl between 48 hours and randomization compared to placebo [2.5 ng/ml (−17.3; 22.5) vs 0.7 ng/ml (−31.77; 25.15), p = 0.77] and the incidence of AKI was similar. Inflammatory cytokines levels were not influenced by EPO treatment. Mortality and hospital stays were similar between the groups and no adverse event was recorded. Conclusion In this randomized-controlled trial, α-Epoetin administrated after cardiac surgery, although safe, demonstrated neither nephroprotective nor anti-inflammatory properties. Trial registration number NCT00676234
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- 2012
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23. Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study
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Arlet Jean-Benoît, Ribeil Jean-Antoine, Chatellier Gilles, Eladari Dominique, De Seigneux Sophie, Souberbielle Jean-Claude, Friedlander Gérard, de Montalembert Marianne, Pouchot Jacques, Prié Dominique, and Courbebaisse Marie
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Sickle cell disease ,Glomerular hyperfiltration ,Albuminuria ,Glomerular filtration rate ,CKD-EPI equation ,Iohexol plasma clearance ,Ethnicity ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients. Methods We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Results Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. Conclusions We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.
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- 2012
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24. Oxalate nephropathy induced by octreotide treatment for acromegaly: a case report
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Gariani Karim, de Seigneux Sophie, Courbebaisse Marie, Lévy Marc, Moll Solange, and Martin Pierre-Yves
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Oxalate nephropathy ,Octreotide ,Antibiotics ,Oxalobacter formigenes ,Medicine - Abstract
Abstract Introduction Oxalate nephropathy has various etiologies and remains a rare cause of renal failure. To the best of our knowledge, we report the first case of oxalate nephropathy following octreotide therapy. Case presentation We report the case of a 78-year-old Caucasian man taking chronic octreotide treatment for acromegaly who presented with acute oxalate nephropathy after antibiotic therapy. The diagnosis was confirmed by urinary analysis and a kidney biopsy. The recovery of renal function was favorable after hydration and withdrawal of octreotide therapy. Conclusions Oxalate nephropathy should be suspected in patients at risk who present with acute kidney injury after prolonged antibiotic treatment. This diagnosis should be distinguished from immuno-allergic interstitial nephritis and requires specific care. The evolution of this condition may be favorable if the pathology is identified correctly. Octreotide therapy should be considered a risk factor for enteric oxaluria.
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- 2012
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25. Clinical prediction model for prognosis in kidney transplant recipients (KIDMO): study protocol
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Schwab, Simon, Sidler, Daniel, Haidar, Fadi, Kuhn, Christian, Schaub, Stefan, Koller, Michael, Mellac, Katell, Stürzinger, Ueli, Tischhauser, Bruno, Binet, Isabelle, Golshayan, Déla, Müller, Thomas, Elmer, Andreas, Franscini, Nicola, Krügel, Nathalie, Fehr, Thomas, Immer, Franz, Swisstransplant Kidney Working Group (STAN), Swiss Transplant Cohort Study, Amico, P., Folie, P., Gannagé, M., Matter, M., Nilsson, J., Peloso, A., de Rougemont, O., Schnyder, A., Spartà, G., Storni, F., Villard, J., Wirth-Müller, U., Wolff, T., Aubert, J.D., Banz, V., Beckmann, S., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Bochud, P.Y., Branca, S., Bucher, H., Catana, E., Cairoli, A., Chalandon, Y., De Geest, S., De Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Ferrari-Lacraz, S., Garzoni, C., Goossens, N., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hirt, P., Hoessly, L., Hofbauer, G., Huynh-Do, U., Laesser, B., Lamoth, F., Lehmann, R., Leichtle, A., Manuel, O., Marti, H.P., Martinelli, M., McLin, V., Merçay, A., Mettler, K., Mueller, N.J., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Passweg, J., Pazeller, R., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Scherrer, A., Schuurmans, M., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirnimann, G., Van Delden, C., Venetz, J.P., Vionnet, J., Wick, M., Wilhelm, M., and Yerly, P.
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Microbiology (medical) ,Immunology ,Immunology and Allergy ,610 Medicine & health ,Estimated glomerular filtration rate ,Graft survival ,Kidney transplantation ,Patient-reported health status ,Prediction model ,Prognosis ,Prognostic model ,Quality of life ,Risk calculator ,Risk score ,eGFR ,610 Medizin und Gesundheit - Abstract
Background Many potential prognostic factors for predicting kidney transplantation outcomes have been identified. However, in Switzerland, no widely accepted prognostic model or risk score for transplantation outcomes is being routinely used in clinical practice yet. We aim to develop three prediction models for the prognosis of graft survival, quality of life, and graft function following transplantation in Switzerland. Methods The clinical kidney prediction models (KIDMO) are developed with data from a national multi-center cohort study (Swiss Transplant Cohort Study; STCS) and the Swiss Organ Allocation System (SOAS). The primary outcome is the kidney graft survival (with death of recipient as competing risk); the secondary outcomes are the quality of life (patient-reported health status) at 12 months and estimated glomerular filtration rate (eGFR) slope. Organ donor, transplantation, and recipient-related clinical information will be used as predictors at the time of organ allocation. We will use a Fine & Gray subdistribution model and linear mixed-effects models for the primary and the two secondary outcomes, respectively. Model optimism, calibration, discrimination, and heterogeneity between transplant centres will be assessed using bootstrapping, internal-external cross-validation, and methods from meta-analysis. Discussion Thorough evaluation of the existing risk scores for the kidney graft survival or patient-reported outcomes has been lacking in the Swiss transplant setting. In order to be useful in clinical practice, a prognostic score needs to be valid, reliable, clinically relevant, and preferably integrated into the decision-making process to improve long-term patient outcomes and support informed decisions for clinicians and their patients. The state-of-the-art methodology by taking into account competing risks and variable selection using expert knowledge is applied to data from a nationwide prospective multi-center cohort study. Ideally, healthcare providers together with patients can predetermine the risk they are willing to accept from a deceased-donor kidney, with graft survival, quality of life, and graft function estimates available for their consideration. Study registration Open Science Framework ID: z6mvj
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- 2023
26. Developing and testing a Corona VaccinE tRiAL pLatform (COVERALL) to study Covid-19 vaccine response in immunocompromised patients
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Katharina, Kusejko, Frédérique, Chammartin, Daniel, Smith, Marc, Odermatt, Julian, Schuhmacher, Michael, Koller, Huldrych F, Günthard, Matthias, Briel, Heiner C, Bucher, Benjamin, Speich, Patrick, Yerly, Swiss HIV Cohort Study, Swiss Transplant Cohort Study, Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Yerly, S., Amico, P., Aubert, J.D., Banz, V., Beckmann, S., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Catana, E., Cairoli, A., Chalandon, Y., De Geest, S., De Rougemont, O., De Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Golshayan, D., Goossens, N., Halter, FHJ, Heim, D., Hess, C., Hillinger, S., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lamoth, F., Lehmann, R., Leichtle, A., Manuel, O., Marti, H.P., Martinelli, M., McLin, V., Mellac, K., Merçay, A., Mettler, K., Müller, A., Mueller, N.J., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Passweg, J., Pazeller, R., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Schanz, U., Schaub, S., Scherrer, A., Schnyder, A., Schuurmans, M., Schwab, S., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirnimann, G., Stürzinger, U., Van Delden, C., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhelm, M., Yerly, P., University of Zurich, and Kusejko, Katharina
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10028 Institute of Medical Virology ,COVID-19 Vaccines ,SARS-CoV-2 ,COVID-19 ,610 Medicine & health ,2725 Infectious Diseases ,10234 Clinic for Infectious Diseases ,Cohort Studies ,Immunocompromised Host ,Treatment Outcome ,10032 Clinic for Oncology and Hematology ,10209 Clinic for Cardiology ,Humans ,10178 Clinic for Pneumology ,COVID-19/prevention & control ,HIV ,Immunocompromised ,REDCap ,Transplant patients ,Trial platform - Abstract
BACKGROUND The rapid course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic calls for fast implementation of clinical trials to assess the effects of new treatment and prophylactic interventions. Building trial platforms embedded in existing data infrastructures is an ideal way to address such questions within well-defined subpopulations. METHODS We developed a trial platform building on the infrastructure of two established national cohort studies: the Swiss human immunodeficiency virus (HIV) Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS). In a pilot trial, termed Corona VaccinE tRiAL pLatform (COVERALL), we assessed the vaccine efficacy of the first two licensed SARS-CoV-2 vaccines in Switzerland and the functionality of the trial platform. RESULTS Using Research Electronic Data Capture (REDCap), we developed a trial platform integrating the infrastructure of the SHCS and STCS. An algorithm identifying eligible patients, as well as baseline data transfer ensured a fast inclusion procedure for eligible patients. We implemented convenient re-directions between the different data entry systems to ensure intuitive data entry for the participating study personnel. The trial platform, including a randomization algorithm ensuring balance among different subgroups, was continuously adapted to changing guidelines concerning vaccination policies. We were able to randomize and vaccinate the first trial participant the same day we received ethics approval. Time to enroll and randomize our target sample size of 380 patients was 22 days. CONCLUSION Taking the best of each system, we were able to flag eligible patients, transfer patient information automatically, randomize and enroll the patients in an easy workflow, decreasing the administrative burden usually associated with a trial of this size.
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- 2022
27. Surgical site infections after simultaneous pancreas kidney and pancreas transplantation in the Swiss Transplant Cohort Study
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P.W. Schreiber, M. Laager, K. Boggian, D. Neofytos, C. van Delden, A. Egli, M. Dickenmann, C. Hirzel, O. Manuel, M. Koller, S. Rossi, B. Schmied, L. Gürke, M. Matter, T. Berney, O. de Rougemont, S.P. Kuster, S. Stampf, N.J. Mueller, P. Amico, J-D. Aubert, V. Banz, S. Beckmann, G. Beldi, C. Berger, E. Berishvili, A. Berzigotti, I. Binet, P-Y. Bochud, S. Branca, H. Bucher, E. Catana, A. Cairoli, Y. Chalandon, S. De Geest, O. De Rougemont, S. De Seigneux, J.L. Dreifuss, M. Duchosal, T. Fehr, S. Ferrari-Lacraz, C. Garzoni, D. Golshayan, N. Goossens, F.H.J. Halter, D. Heim, C. Hess, S. Hillinger, H.H. Hirsch, P. Hirt, G. Hofbauer, U. Huynh-Do, F. Immer, B. Laesser, F. Lamoth, R. Lehmann, A. Leichtle, H.P. Marti, M. Martinelli, V. McLin, K. Mellac, A. Merçay, K. Mettler, A. Müller, U. Müller-Arndt, B. Müllhaupt, M. Nägeli, G. Oldani, M. Pascual, J. Passweg, R. Pazeller, K. Posfay-Barbe, J. Rick, A. Rosselet, S. Rothlin, F. Ruschitzka, T. Schachtner, U. Schanz, S. Schaub, A. Scherrer, A. Schnyder, M. Schuurmans, S. Schwab, T. Sengstag, F. Simonetta, J. Steiger, G. Stirnimann, U. Stürzinger, C. Van Delden, J-P. Venetz, J. Villard, J. Vionnet, M. Wick, M. Wilhelm, P. Yerly, Swiss Transplant Cohort Study, Amico, P., Aubert, J.D., Banz, V., Beckmann, S., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Catana, E., Cairoli, A., Chalandon, Y., De Geest, S., De Rougemont, O., De Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Garzoni, C., Golshayan, D., Goossens, N., Halter, FHJ, Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lamoth, F., Lehmann, R., Leichtle, A., Manuel, O., Marti, H.P., Martinelli, M., McLin, V., Mellac, K., Merçay, A., Mettler, K., Müller, A., Mueller, N.J., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Passweg, J., Pazeller, R., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Schanz, U., Schaub, S., Scherrer, A., Schnyder, A., Schuurmans, M., Schwab, S., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirnimann, G., Stürzinger, U., Van Delden, C., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhelm, M., and Yerly, P.
- Subjects
Microbiology (medical) ,Adult ,610 Medicine & health ,General Medicine ,Kidney ,Cohort Studies ,Humans ,Kidney Transplantation/adverse effects ,Pancreas ,Pancreas Transplantation/adverse effects ,Risk Factors ,Surgical Wound Infection/epidemiology ,Surgical Wound Infection/etiology ,Switzerland/epidemiology ,Hospital-acquired infection ,Pancreas transplantation ,Simultaneous kidney–pancreas transplantation ,Surgical site infection ,Kidney Transplantation ,Infectious Diseases ,Surgical Wound Infection ,Pancreas Transplantation ,Switzerland - Abstract
BACKGROUND Among hospital-acquired infections, surgical site infections (SSIs) are frequent. SSI in the early post-transplant course poses a relevant threat to transplant recipients. AIM To determine incidence, risk factors for SSI and its association with post-transplant outcomes and pancreas transplant (P-Tx) recipients. METHODS Adult simultaneous kidney-pancreas transplantation (SPK-T) and P-Tx recipients with a follow-up of at least 90 days were identified in the Swiss Transplant Cohort Study (STCS) dataset. Except for the categorization of SSIs according to Centers for Disease Control and Prevention (CDC) criteria, all other data were prospectively collected. Risk factors for SSI were investigated with logistic regression. A Weibull accelerated failure-time model was applied to address the impact of SSI on length of stay, correcting for transplant-related complications and delayed graft function. FINDINGS Of 130 transplant recipients, 108 SPK-Tx and 22 P-Tx, 18 (14%) individuals developed SSI within the first 90 days after transplantation. Deep incisional (seven, 38.9%) and organ/space infections (eight, 44.4%) predominated. In the majority of SSIs (11, 61.1%; two SSIs with simultaneous identification of fungal pathogens) bacteria were detected with Enterococcus spp. being most frequent. The median duration of hospitalization after transplantation was significantly longer in recipients with SSI (median: 26 days; interquartile range (IQR): 19-44) than in patients without SSI (median: 17 days; IQR: 12-25; P = 0.002). In multivariate analysis, SSI was significantly associated with increased length of stay and prolonged the duration of hospitalization by 36% (95% confidence interval: 4-79). CONCLUSION SSI after SPK-Tx and P-Tx occurred at a frequency of 14%. Among pathogens, Enterococcus spp. predominated. SSI was independently associated with a longer hospitalization after transplantation.
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- 2022
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28. [Management of chronic kidney disease in primary care: New practical guidelines in primary care].
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Silvano A, Di Taranto P, Fiorentini S, De Seigneux S, and Senchyna A
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- Humans, Primary Health Care standards, Practice Guidelines as Topic, Renal Insufficiency, Chronic therapy, Renal Insufficiency, Chronic complications
- Abstract
Chronic kidney disease is often encountered in clinical practice, affecting between 8 and 16% of the world's population. Screening for CKD represents a major challenge for patients, given the increase in morbidity and mortality associated with the disease, as well as a public health issue in terms of slowing the progression to end-stage renal failure, which requires costly replacement treatments (dialysis and transplantation). The new KDIGO guidelines suggest aiming for optimal control of the cardiovascular risk factors associated with chronic kidney disease, in particular with the help of emerging treatments such as SGLT2 inhibitors. This article summarises the latest nephroprotection recommendations for primary care physicians., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
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- 2024
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29. Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria.
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Faivre A, Bugarski M, Rinaldi A, Sakhi IB, Verissimo T, Legouis D, Rutkowski JM, Correia S, Kaminska M, Dalga D, Malpetti D, Cippa PE, de Seigneux S, and Hall AM
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- Humans, Animals, Proteinuria etiology, Proteinuria physiopathology, Kidney Tubules pathology, Kidney Tubules physiopathology, Kidney Glomerulus physiopathology, Kidney Glomerulus pathology
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- 2024
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30. The role of hypoxia in chronic kidney disease: a nuanced perspective.
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Faivre A and de Seigneux S
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- Humans, Animals, Kidney metabolism, Kidney drug effects, Sodium-Glucose Transporter 2 Inhibitors therapeutic use, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Signal Transduction drug effects, Renal Insufficiency, Chronic metabolism, Renal Insufficiency, Chronic drug therapy, Renal Insufficiency, Chronic complications, Hypoxia metabolism
- Abstract
Purpose of Review: This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease., Recent Findings: Emerging evidence challenges the traditional view that hypoxia is universally harmful in CKD context. We review here the recent evidence about hypoxia and HIF activation in CKD. We also discuss the effect of hypoxia on the renal tissue, and the relative inhibition of different HIF isoforms. Recent advancements in therapies, such as HIF prolyl hydroxylase inhibitors (HIF-PHIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors seem to target the HIF pathway. These drugs impact anemia associated with CKDbut also renoprotection, hinting at a more complex interplay between hypoxia, HIF activation, and renal health., Summary: A certain level of hypoxia and specific HIF pathway activation, especially HIF-α, can be beneficial in CKD progression. Therapeutic strategies targeting HIF stabilization, such as with HIF-PHIs and SGLT2 inhibitors, offer promising avenues for enhancing renal protection. Future investigations should aim at better understanding the precise effects on HIF pathway and optimize their clinical application to improve outcomes for CKD patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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31. Acute Kidney Injury and Hair-Straightening Products.
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Huber A, Deffert C, Moll S, de Seigneux S, and Berchtold L
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- 2024
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32. Pitfalls in Valganciclovir Prophylaxis Dose Adjustment Based on Renal Function in Kidney Transplant Recipients.
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Hammer N, Hoessly L, Haidar F, Hirzel C, de Seigneux S, van Delden C, Vogt B, Sidler D, and Neofytos D
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Adult, Aged, Kidney drug effects, Transplant Recipients, Valganciclovir administration & dosage, Valganciclovir therapeutic use, Kidney Transplantation adverse effects, Cytomegalovirus Infections prevention & control, Antiviral Agents administration & dosage, Antiviral Agents adverse effects
- Abstract
Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing ( p = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, p = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hammer, Hoessly, Haidar, Hirzel, de Seigneux, van Delden, Vogt, Sidler and Neofytos.)
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- 2024
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33. Prevalence of Drug Use in Ultraendurance Athletes.
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Robach P, Trebes G, Buisson C, Mechin N, Mazzarino M, Garribba F, Roustit M, Quesada JL, Lefèvre B, Giardini G, DE Seigneux S, Botré F, and Bouzat P
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- Humans, Male, Female, Acetaminophen, Prevalence, Anti-Inflammatory Agents, Non-Steroidal, Athletes, Doping in Sports, Substance-Related Disorders
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Purpose: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires., Methods: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start of ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use., Results: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared., Conclusions: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes., (Copyright © 2024 by the American College of Sports Medicine.)
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- 2024
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34. [Renal xenotransplantation : state of the art].
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Nachit M, Masson G, Haidar F, and De Seigneux S
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- Animals, Humans, Transplantation, Heterologous, Graft Rejection prevention & control, Kidney, Kidney Failure, Chronic
- Abstract
Xenotransplantation could be an inexhaustible source of organs and change the life of end-stage kidney disease patients with reduction of morbidity and mortality. Through genetic engineering it is now possible to reduce the risk of hyperacute and acute graft rejection and improve the overall immune compatibility between two different species. Some experiments have already brought promising perspectives. Nevertheless, there are still difficulties to overcome. The risk of animal-related infectious diseases, ethnic limitations, safety, and applicability of large-scale xenotransplantation should be assessed. We still need to improve the technical aspects and define the purpose of these procedures: definitive replacement or temporary solution?, Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
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- 2024
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35. [Kidney disease in antiphospholipid antibody syndrome].
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Scheen M, Cordes L, Haidar F, and De Seigneux S
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- Humans, Anticoagulants therapeutic use, Rare Diseases, Antiphospholipid Syndrome complications, Antiphospholipid Syndrome diagnosis, Antiphospholipid Syndrome therapy, Autoimmune Diseases, Renal Artery Obstruction, Venous Thromboembolism
- Abstract
Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêt en relation avec cet article.
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- 2024
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36. Néphrologie de précision.
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De Seigneux S and Fakhouri F
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- 2024
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37. A transfer learning framework to elucidate the clinical relevance of altered proximal tubule cell states in kidney disease.
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Legouis D, Rinaldi A, Malpetti D, Arnoux G, Verissimo T, Faivre A, Mangili F, Rinaldi A, Ruinelli L, Pugin J, Moll S, Clivio L, Bolis M, de Seigneux S, Azzimonti L, and Cippà PE
- Abstract
The application of single-cell technologies in clinical nephrology remains elusive. We generated an atlas of transcriptionally defined cell types and cell states of human kidney disease by integrating single-cell signatures reported in the literature with newly generated signatures obtained from 5 patients with acute kidney injury. We used this information to develop kidney-specific cell-level information ExtractoR (K-CLIER), a transfer learning approach specifically tailored to evaluate the role of cell types/states on bulk RNAseq data. We validated the K-CLIER as a reliable computational framework to obtain a dimensionality reduction and to link clinical data with single-cell signatures. By applying K-CLIER on cohorts of patients with different kidney diseases, we identified the most relevant cell types associated with fibrosis and disease progression. This analysis highlighted the central role of altered proximal tubule cells in chronic kidney disease. Our study introduces a new strategy to exploit the power of single-cell technologies toward clinical applications., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)
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- 2024
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38. Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21.
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Agius T, Emsley R, Lyon A, MacArthur MR, Kiesworo K, Faivre A, Stavart L, Lambelet M, Legouis D, de Seigneux S, Golshayan D, Lazeyras F, Yeh H, Markmann JF, Uygun K, Ocampo A, Mitchell SJ, Allagnat F, Déglise S, and Longchamp A
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- Animals, Female, Humans, Male, Mice, Dietary Carbohydrates metabolism, Dietary Proteins metabolism, Liver surgery, Liver metabolism, Mice, Inbred C57BL, Diet, Carbohydrate Loading, Fibroblast Growth Factors metabolism, Reperfusion Injury metabolism, Surgical Procedures, Operative
- Abstract
Dietary restriction promotes resistance to surgical stress in multiple organisms. Counterintuitively, current medical protocols recommend short-term carbohydrate-rich drinks (carbohydrate loading) prior to surgery, part of a multimodal perioperative care pathway designed to enhance surgical recovery. Despite widespread clinical use, preclinical and mechanistic studies on carbohydrate loading in surgical contexts are lacking. Here we demonstrate in ad libitum-fed mice that liquid carbohydrate loading for one week drives reductions in solid food intake, while nearly doubling total caloric intake. Similarly, in humans, simple carbohydrate intake is inversely correlated with dietary protein intake. Carbohydrate loading-induced protein dilution increases expression of hepatic fibroblast growth factor 21 (FGF21) independent of caloric intake, resulting in protection in two models of surgical stress: renal and hepatic ischemia-reperfusion injury. The protection is consistent across male, female, and aged mice. In vivo, amino acid add-back or genetic FGF21 deletion blocks carbohydrate loading-mediated protection from ischemia-reperfusion injury. Finally, carbohydrate loading induction of FGF21 is associated with the induction of the canonical integrated stress response (ATF3/4, NF-kB), and oxidative metabolism (PPARγ). Together, these data support carbohydrate loading drinks prior to surgery and reveal an essential role of protein dilution via FGF21., (© 2024. The Author(s).)
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- 2024
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39. New evidence of the impact of mitochondria on kidney health and disease.
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Verissimo T and de Seigneux S
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- Humans, Kidney metabolism, Mitochondria
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- 2024
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40. [Nephrology: what's new in 2023].
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De Seigneux S, Haidar F, Jaques D, Masson G, Nachit M, and Saudan P
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- Humans, Renal Dialysis, Nephrology, Acute Kidney Injury therapy, Heart Failure, Kidney Transplantation
- Abstract
Molecules such as sparsentan and budesonide look promising to treat proteinuric IGA nephropathy. SLGT2 inhibitors have a prominent place in nephroprotection and could be used in the treatment of acute kidney injury due to heart failure as well. High volume hemodiafiltration compared to hemodialysis improves survival in dialysis patients. Lessening dialysate temperature does not improve hemodynamic stability during the dialysis session. Sodium bicarbonate does not seem to protect renal function in renal transplant patients. SGLT2 inhibitors may have a beneficial effect in these patients in terms of nephroprotection., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
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- 2024
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41. Evolution of hypoxia and hypoxia-inducible factor asparaginyl hydroxylase regulation in chronic kidney disease.
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Faivre A, Dissard R, Kuo W, Verissimo T, Legouis D, Arnoux G, Heckenmeyer C, Fernandez M, Tihy M, Rajaram RD, Delitsikou V, Le NA, Spingler B, Mueller B, Shulz G, Lindenmeyer M, Cohen C, Rutkowski JM, Moll S, Scholz CC, Kurtcuoglu V, and de Seigneux S
- Subjects
- Humans, Animals, Mice, X-Ray Microtomography, Repressor Proteins genetics, Down-Regulation, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Hypoxia
- Abstract
Background: The roles of hypoxia and hypoxia inducible factor (HIF) during chronic kidney disease (CKD) are much debated. Interventional studies with HIF-α activation in rodents have yielded contradictory results. The HIF pathway is regulated by prolyl and asparaginyl hydroxylases. While prolyl hydroxylase inhibition is a well-known method to stabilize HIF-α, little is known about the effect asparaginyl hydroxylase factor inhibiting HIF (FIH)., Methods: We used a model of progressive proteinuric CKD and a model of obstructive nephropathy with unilateral fibrosis. In these models we assessed hypoxia with pimonidazole and vascularization with three-dimensional micro-computed tomography imaging. We analysed a database of 217 CKD biopsies from stage 1 to 5 and we randomly collected 15 CKD biopsies of various severity degrees to assess FIH expression. Finally, we modulated FIH activity in vitro and in vivo using a pharmacologic approach to assess its relevance in CKD., Results: In our model of proteinuric CKD, we show that early CKD stages are not characterized by hypoxia or HIF activation. At late CKD stages, some areas of hypoxia are observed, but these are not colocalizing with fibrosis. In mice and in humans, we observed a downregulation of the HIF pathway, together with an increased FIH expression in CKD, according to its severity. Modulating FIH in vitro affects cellular metabolism, as described previously. In vivo, pharmacologic FIH inhibition increases the glomerular filtration rate of control and CKD animals and is associated with decreased development of fibrosis., Conclusions: The causative role of hypoxia and HIF activation in CKD progression is questioned. A pharmacological approach of FIH downregulation seems promising in proteinuric kidney disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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42. [Management of genetic renal disorders: local experience and importance of the network].
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Bonny O, Ketterer A, Hermida S, Superti-Furga A, Venetz JP, Chehade H, Fodstad H, Cina V, Parvex P, Paoloni-Giacobino A, De Seigneux S, and Fakhouri F
- Subjects
- Adult, Child, Humans, Kidney, Ambulatory Care Facilities, Hospitals, University, Rare Diseases therapy, Kidney Diseases genetics, Kidney Diseases therapy, Nephrology
- Abstract
In nephrology, rare disorders are frequently encountered. In children, about 60% of the renal disorders are rare, with congenital abnormalities of the kidney and urinary tract disorders (CAKUT), being highly prevalent. In adults, about 22% of the disorders leading to renal replacement therapies are rare and include glomerulonephritis and genetic disorders. Rarity may preclude the rapid and extensive access to care for patients suffering of renal disorders, especially in Switzerland, which is small and fragmented. Only collaborative network and access to databases, shared resources and to specific competence may help patient management. Lausanne and Geneva University Hospitals have started specialized outpatient clinics for rare renal disorders several years ago and are part of national and international networks., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.
- Published
- 2023
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43. Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.
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Hammer N, Legouis D, Pasch A, Huber A, Al-Qusairi L, Martin PY, de Seigneux S, and Berchtold L
- Abstract
Background: Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients., Methods: We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%., Results: During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 ( p value = 0.17), FEP/FGF23 ( p value = 0.78), TRP ( p value = 0.62) and Klotho ( p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 ( p = 0.048) and remained significant in multivariable analysis., Conclusion: T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.
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- 2023
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44. PCK1 is a key regulator of metabolic and mitochondrial functions in renal tubular cells.
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Verissimo T, Dalga D, Arnoux G, Sakhi I, Faivre A, Auwerx H, Bourgeois S, Paolucci D, Gex Q, Rutkowski JM, Legouis D, Wagner CA, Hall AM, and de Seigneux S
- Subjects
- Animals, Mice, Glucose metabolism, Lactates metabolism, Mitochondria metabolism, Phosphoenolpyruvate metabolism, Phosphoenolpyruvate Carboxykinase (GTP) genetics, Phosphoenolpyruvate Carboxykinase (GTP) metabolism, Acidosis metabolism, Kidney metabolism
- Abstract
Phosphoenolpyruvate carboxykinase 1 (PCK1 or PEPCK-C) is a cytosolic enzyme converting oxaloacetate to phosphoenolpyruvate, with a potential role in gluconeogenesis, ammoniagenesis, and cataplerosis in the liver. Kidney proximal tubule cells display high expression of this enzyme, whose importance is currently not well defined. We generated PCK1 kidney-specific knockout and knockin mice under the tubular cell-specific PAX8 promoter. We studied the effect of PCK1 deletion and overexpression at the renal level on tubular physiology under normal conditions and during metabolic acidosis and proteinuric renal disease. PCK1 deletion led to hyperchloremic metabolic acidosis characterized by reduced but not abolished ammoniagenesis. PCK1 deletion also resulted in glycosuria, lactaturia, and altered systemic glucose and lactate metabolism at baseline and during metabolic acidosis. Metabolic acidosis resulted in kidney injury in PCK1-deficient animals with decreased creatinine clearance and albuminuria. PCK1 further regulated energy production by the proximal tubule, and PCK1 deletion decreased ATP generation. In proteinuric chronic kidney disease, mitigation of PCK1 downregulation led to better renal function preservation. PCK1 is essential for kidney tubular cell acid-base control, mitochondrial function, and glucose/lactate homeostasis. Loss of PCK1 increases tubular injury during acidosis. Mitigating kidney tubular PCK1 downregulation during proteinuric renal disease improves renal function. NEW & NOTEWORTHY Phosphoenolpyruvate carboxykinase 1 (PCK1) is highly expressed in the proximal tubule. We show here that this enzyme is crucial for the maintenance of normal tubular physiology, lactate, and glucose homeostasis. PCK1 is a regulator of acid-base balance and ammoniagenesis. Preventing PCK1 downregulation during renal injury improves renal function, rendering it an important target during renal disease.
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- 2023
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45. Renal involvement in systemic sclerosis.
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Scheen M, Dominati A, Olivier V, Nasr S, De Seigneux S, Mekinian A, Issa N, and Haidar F
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- Humans, Kidney, Angiotensin-Converting Enzyme Inhibitors, Scleroderma, Systemic diagnosis, Acute Kidney Injury diagnosis, Acute Kidney Injury etiology, Scleroderma, Localized complications
- Abstract
Systemic sclerosis is a rare autoimmune vasculopathy associated with dysregulated innate and adaptive immunity that leads to generalized systemic fibrosis. Renal involvement occurs in a significant proportion of systemic sclerosis patients, and is associated with worse outcome. Scleroderma renal crisis (SRC) is the most studied and feared renal complication described in systemic sclerosis. However, with the emergence of ACE inhibitors and better management, the mortality rate of SRC has significantly decreased. Renal disease in systemic sclerosis offers a wide array of differential diagnoses that may be challenging for the clinician. The spectrum of renal manifestations in systemic sclerosis ranges from an isolated decrease in glomerular filtration rate, increased intrarenal arterial stiffness, and isolated proteinuria due to SRC to more rare manifestations such as association with antiphospholipid antibody nephropathy and ANCA-associated vasculitis. The changes observed in the kidneys in systemic sclerosis are thought to be due to a complex interplay of various factors, including renal vasculopathy, as well as the involvement of the complement system, vasoactive mediators such as endothelin-1, autoimmunity, prothrombotic and profibrotic cytokines, among others. This literature review aims to provide an overview of the main renal manifestations in systemic sclerosis by discussing the most recent epidemiological and pathophysiological data available and the challenges for clinicians in making a diagnosis of renal disease in patients with systemic sclerosis., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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46. Association between urinary oxytocin secretion and natriuresis after transsphenoidal pituitary surgery.
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Constanthin PE, Isidor N, De Seigneux S, and Momjian S
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- Humans, Natriuresis, Oxytocin, Sodium, Inappropriate ADH Syndrome etiology, Pituitary Diseases, Hyponatremia etiology
- Abstract
Objective: Oxytocin (OXT) secretion has been shown to be abnormally elevated in patients who develop syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-related hyponatremia after transsphenoidal pituitary surgery (TPS). While OXT was previously reported to increase natriuresis in the kidney, a potential role for this hormone in postoperative sodium balance and dysnatremias has not been studied. The objective of this study was to analyze the correlation between patients' urinary output of OXT and natremia and natriuresis after TPS., Methods: The authors measured and correlated the urinary output of OXT with natriuresis and natremia in 20 consecutive patients who underwent TPS., Results: The ratio of urinary secretion of OXT between days 1 and 4 showed a strong, significant correlation with patient natriuresis at day 7 after pituitary surgery. Concomitantly, patient natremia showed a moderate, inverted correlation with OXT secretion in the urine., Conclusions: Together, these results show for the first time that urinary OXT secretion correlates with patient natriuresis and natremia after pituitary surgery. This observation suggests a notable role for this hormone in sodium balance.
- Published
- 2023
- Full Text
- View/download PDF
47. Variability of 24-Hour Sodium Urinary Excretion in Young Healthy Males Based on Consecutive Urine Collections: Impact on Categorization of Salt Intake.
- Author
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Jaques DA, Ponte B, Olivier V, de Seigneux S, Feraille E, Burnier M, and Pechère-Bertschi A
- Subjects
- Humans, Male, Prospective Studies, Sodium urine, Sodium Chloride, Urine Specimen Collection, Sodium Chloride, Dietary urine, Sodium, Dietary
- Abstract
Objective: Several nonconsecutive 24-h urinary collections are considered the gold standard for estimating dietary salt intake. As those samples are logistically demanding, we aimed to describe the variability of 24-h sodium urinary excretion over consecutive days and report its adequacy with sodium intake., Methods: We enrolled 16 healthy male volunteers in a prospective controlled study. All participants randomly received a low salt diet (LSD) (3 g/day of NaCl), a normal salt diet (NSD) (6 g/day of NaCl), and a high salt diet (HSD) (15 g/day of NaCl) for 7 days in a crossover design without wash-out period., Results: On day 6, median sodium urinary excretion was 258 (216-338), 10 (8-18), and 87 (69-121) mmol/day for HSD, LSD, and NSD, respectively (P < .001). When considering days 4-6, sodium urinary excretion was in steady state as models with and without interaction term "diet type X sample day" were not significantly different (P = .163). On day 6, area under the curve (AUC) of receiver operating characteristic for urinary sodium excretion to detect HSD was 1.0 (1.0-1.0) and a cut-point of 175 mmol/day was 100% sensitive and specific to detect HSD. On day 6, receiver operating characteristic AUC to detect LSD was 0.993 (0.978-1.0) and a cut-point of 53 mmol/day was 96.4% sensitive and 100% specific to detect LSD., Conclusion: A steady state of sodium balance, where sodium intake is proportional to its excretion, is reached within a few days under a constant diet in the real-life setting. Categorization of salt consumption into low (3 g/day), normal (6 g/day), or high (15 g/day) based on a single 24-h urine collection is nearly perfect. Based on these results, repeated nonconsecutive urine collection might prove unnecessary to estimate sodium intake in daily clinical practice provided that diet is rather constant over time., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
48. NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing.
- Author
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Siedlar AM, Seredenina T, Faivre A, Cambet Y, Stasia MJ, André-Lévigne D, Bochaton-Piallat ML, Pittet-Cuénod B, de Seigneux S, Krause KH, Modarressi A, and Jaquet V
- Subjects
- Animals, Humans, Mice, Cell Differentiation, Fibroblasts metabolism, Fibrosis, NADPH Oxidase 4 genetics, NADPH Oxidase 4 metabolism, NADPH Oxidases metabolism, Reactive Oxygen Species metabolism, Transforming Growth Factor beta metabolism, Transforming Growth Factor beta1, Wound Healing, Hydrogen Peroxide metabolism, Myofibroblasts metabolism
- Abstract
Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation of reactive oxygen species (ROS). Myofibroblasts synthesize proteins of the extracellular matrix (ECM) and display a contractile phenotype. Myofibroblasts are predominant contributors of wound healing and several pathological states, including fibrotic diseases and cancer. Inhibition of the ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed to mitigate fibroblast to myofibroblast differentiation and to offer a therapeutic option for the treatment of fibrotic diseases. In this study, we addressed the role of NOX4 in physiological wound healing and in TGF-β-induced myofibroblast differentiation. We explored the phenotypic changes induced by TGF-β in primary skin fibroblasts isolated from Nox4-deficient mice by immunofluorescence, Western blotting and RNA sequencing. Mice deficient for Cyba, the gene coding for p22
phox , a key subunit of NOX4 were used for confirmatory experiments as well as human primary skin fibroblasts. In vivo, the wound healing was similar in wild-type and Nox4-deficient mice. In vitro, despite a strong upregulation following TGF-β treatment, Nox4 did not influence skin myofibroblast differentiation although a putative NOX4 inhibitor GKT137831 and a flavoprotein inhibitor diphenylene iodonium mitigated this mechanism. Transcriptomic analysis revealed upregulation of the mitochondrial protein Ucp2 and the stress-response protein Hddc3 in Nox4-deficient fibroblasts, which had however no impact on fibroblast bioenergetics. Altogether, we provide extensive evidence that NOX4 is dispensable for wound healing and skin fibroblast to myofibroblast differentiation, and suggest that another H2 O2 -generating flavoprotein drives this mechanism., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
49. Gluconeogenesis in the kidney: in health and in chronic kidney disease.
- Author
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Dalga D, Verissimo T, and de Seigneux S
- Abstract
Chronic kidney disease (CKD) is a global health issue with increasing prevalence. Despite large improvements in current therapies, slowing CKD progression remains a challenge. A better understanding of renal pathophysiology is needed to offer new therapeutic targets. The role of metabolism alterations and mitochondrial dysfunction in tubular cells is increasingly recognized in CKD progression. In proximal tubular cells, CKD progression is associated with a switch from fatty acid oxidation to glycolysis. Glucose synthesis through gluconeogenesis is one of the principal physiological functions of the kidney. Loss of tubular gluconeogenesis in a stage-dependent manner is a key feature of CKD and contributes to systemic and possibly local metabolic complications. The local consequences observed may be related to an accumulation of precursors, such as glycogen, but also to the various physiological functions of the gluconeogenesis enzymes. The basic features of metabolism in proximal tubular cells and their modifications during CKD will be reviewed. The metabolic modifications and their influence on kidney disease will be described, as well as the local and systemic consequences. Finally, therapeutic interventions will be discussed., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2023
- Full Text
- View/download PDF
50. La néphrologie : une spécialité de maladies rares.
- Author
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Fakhouri F and De Seigneux S
- Subjects
- Humans, Rare Diseases, Nephrology, Medicine
- Published
- 2023
- Full Text
- View/download PDF
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