26 results on '"Seigneux, Sophie de"'
Search Results
2. Gluconeogenesis in the kidney: in health and in chronic kidney disease.
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Dalga, Delal, Verissimo, Thomas, and Seigneux, Sophie de
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CHRONIC kidney failure ,GLUCONEOGENESIS ,FATTY acid oxidation ,GLUCOSE synthesis ,KIDNEY diseases - 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. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI
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Gupta, Shruti, primary, Garcia-Carro, Clara, additional, Prosek, Jason M, additional, Glezerman, Ilya, additional, Herrmann, Sandra M, additional, Garcia, Pablo, additional, Abudayyeh, Ala, additional, Lumlertgul, Nuttha, additional, Malik, A Bilal, additional, Loew, Sebastian, additional, Beckerman, Pazit, additional, Renaghan, Amanda D, additional, Carlos, Christopher A, additional, Rashidi, Arash, additional, Mithani, Zain, additional, Deshpande, Priya, additional, Rangarajan, Sunil, additional, Shah, Chintan V, additional, Seigneux, Sophie De, additional, Campedel, Luca, additional, Kitchlu, Abhijat, additional, Shin, Daniel Sanghoon, additional, Coppock, Gaia, additional, Ortiz-Melo, David I, additional, Sprangers, Ben, additional, Aggarwal, Vikram, additional, Benesova, Karolina, additional, Wanchoo, Rimda, additional, Murakami, Naoka, additional, Cortazar, Frank B, additional, Reynolds, Kerry L, additional, Sise, Meghan E, additional, Soler, Maria Jose, additional, and Leaf, David E, additional
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- 2022
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4. TREATMENT OF PERSISTENT RENAL DYSFUNCTION AFTER PREECLAMPSIA WITH BENAZEPRIL: A RANDOMIZED, DOUBLE-BLIND TRIAL
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Pechère-Bertschi, Antoinette, primary, Dufey, Anne, additional, Wuerzner, Gregoire, additional, Jaques, David, additional, Burnier, Michel, additional, Tejada, Begonia Martinez De, additional, Seigneux, Sophie De, additional, and Ponte, Belén, additional
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- 2022
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5. Acute kidney injury in patients treated with immune checkpoint inhibitors
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Gupta, Shruti, Short, Samuel AP, Sise, Meghan E, Prosek, Jason M, Madhavan, Sethu M, Soler, Maria Jose, Ostermann, Marlies, Herrmann, Sandra M, Abudayyeh, Ala, Anand, Shuchi, Glezerman, Ilya, Motwani, Shveta S, Murakami, Naoka, Wanchoo, Rimda, Ortiz-Melo, David I, Rashidi, Arash, Sprangers, Ben, Aggarwal, Vikram, Malik, A Bilal, Loew, Sebastian, Carlos, Christopher A, Chang, Wei-Ting, Beckerman, Pazit, Mithani, Zain, Shah, Chintan V, Renaghan, Amanda D, Seigneux, Sophie De, Campedel, Luca, Kitchlu, Abhijat, Shin, Daniel Sanghoon, Rangarajan, Sunil, Deshpande, Priya, Coppock, Gaia, Eijgelsheim, Mark, Seethapathy, Harish, Lee, Meghan D, Strohbehn, Ian A, Owen, Dwight H, Husain, Marium, Garcia-Carro, Clara, Bermejo, Sheila, Lumlertgul, Nuttha, Seylanova, Nina, Flanders, Lucy, Isik, Busra, Mamlouk, Omar, Lin, Jamie S, Garcia, Pablo, Kaghazchi, Aydin, Khanin, Yuriy, Kansal, Sheru K, Wauters, Els, Chandra, Sunandana, Schmidt-Ott, Kai M, Hsu, Raymond K, Tio, Maria C, Sarvode Mothi, Suraj, Singh, Harkarandeep, Schrag, Deborah, Jhaveri, Kenar D, Reynolds, Kerry L, Cortazar, Frank B, Leaf, David E, and ICPi-AKI Consortium Investigators
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Male ,CTLA-4 antigen ,Kidney Disease ,Renal and urogenital ,ICPi-AKI Consortium Investigators ,Evaluation of treatments and therapeutic interventions ,Middle Aged ,Acute Kidney Injury ,programmed cell death 1 receptor ,Cohort Studies ,Good Health and Well Being ,Risk Factors ,6.1 Pharmaceuticals ,Humans ,Female ,immunotherapy ,Immune Checkpoint Inhibitors ,Aged - Abstract
BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
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- 2021
6. Acute kidney injury in patients treated with immune checkpoint inhibitors
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Gupta, Shruti, primary, Short, Samuel A P, additional, Sise, Meghan E, additional, Prosek, Jason M, additional, Madhavan, Sethu M, additional, Soler, Maria Jose, additional, Ostermann, Marlies, additional, Herrmann, Sandra M, additional, Abudayyeh, Ala, additional, Anand, Shuchi, additional, Glezerman, Ilya, additional, Motwani, Shveta S, additional, Murakami, Naoka, additional, Wanchoo, Rimda, additional, Ortiz-Melo, David I, additional, Rashidi, Arash, additional, Sprangers, Ben, additional, Aggarwal, Vikram, additional, Malik, A Bilal, additional, Loew, Sebastian, additional, Carlos, Christopher A, additional, Chang, Wei-Ting, additional, Beckerman, Pazit, additional, Mithani, Zain, additional, Shah, Chintan V, additional, Renaghan, Amanda D, additional, Seigneux, Sophie De, additional, Campedel, Luca, additional, Kitchlu, Abhijat, additional, Shin, Daniel Sanghoon, additional, Rangarajan, Sunil, additional, Deshpande, Priya, additional, Coppock, Gaia, additional, Eijgelsheim, Mark, additional, Seethapathy, Harish, additional, Lee, Meghan D, additional, Strohbehn, Ian A, additional, Owen, Dwight H., additional, Husain, Marium, additional, Garcia-Carro, Clara, additional, Bermejo, Sheila, additional, Lumlertgul, Nuttha, additional, Seylanova, Nina, additional, Flanders, Lucy, additional, Isik, Busra, additional, Mamlouk, Omar, additional, Lin, Jamie S, additional, Garcia, Pablo, additional, Kaghazchi, Aydin, additional, Khanin, Yuriy, additional, Kansal, Sheru K, additional, Wauters, Els, additional, Chandra, Sunandana, additional, Schmidt-Ott, Kai M, additional, Hsu, Raymond K, additional, Tio, Maria C, additional, Sarvode Mothi, Suraj, additional, Singh, Harkarandeep, additional, Schrag, Deborah, additional, Jhaveri, Kenar D, additional, Reynolds, Kerry L, additional, Cortazar, Frank B, additional, and Leaf, David E, additional
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- 2021
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7. Impact of Hyponatremia after Renal Transplantation on Decline of Renal Function, Graft Loss and Patient Survival: A Prospective Cohort Study
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Berchtold, Lena, Filzer, Anja, Achermann, Rita, Devetzis, Vasileios, Dahdal, Suzan, Bonani, Marco, Schnyder, Aurelia, Golshayan, Dela, Amico, Patrizia, Huynh-Do, Uyen, Seigneux, Sophie de, Arampatzis, Spyridon, Collaborators, on behalf of Swiss Transplant Cohort Study, University of Zurich, and Arampatzis, Spyridon
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,hyponatremia ,Renal function ,kidney transplantation ,610 Medicine & health ,Kidney ,Gastroenterology ,Article ,Cohort Studies ,Swiss Transplant Cohort Study ,Internal medicine ,Medicine ,Humans ,TX341-641 ,10035 Clinic for Nephrology ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,1106 Food Science ,Nutrition and Dietetics ,business.industry ,Nutrition. Foods and food supply ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Survival Analysis ,Transplant Recipients ,Transplantation ,Log-rank test ,medicine.anatomical_structure ,Ambulatory ,2916 Nutrition and Dietetics ,Female ,business ,Hyponatremia ,Switzerland ,Food Science - Abstract
Background: Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. Methods: This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. Results: Mean sodium was 140 +/− 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 +/− 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02, p = 0.97, 95% CI: 0.47–2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). Conclusions: Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.
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- 2021
8. Outcomes of incident patients treated with incremental haemodialysis as compared with standard haemodialysis and peritoneal dialysis.
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Jaques, David A, Ponte, Belen, Haidar, Fadi, Dufey, Anne, Carballo, Sebastian, Seigneux, Sophie De, and Saudan, Patrick
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PERITONEAL dialysis ,RENAL replacement therapy ,HEMODIALYSIS ,TREATMENT effectiveness ,HEMODIALYSIS patients - Abstract
Background Residual kidney function is considered better preserved with incremental haemodialysis (I-HD) or peritoneal dialysis (PD) as compared with conventional thrice-weekly HD (TW-HD) and is associated with improved survival. We aimed to describe outcomes of patients initiating dialysis with I-HD, TW-HD or PD. Methods We conducted a retrospective analysis of a prospectively assembled cohort in a single university centre including all adults initiating dialysis from January 2013 to December 2020. Primary and secondary endpoints were overall survival and hospitalization days at 1 year, respectively. Results We included 313 patients with 234 starting on HD (166 TW-HD and 68 I-HD) and 79 on PD. At the end of the study, 10 were still on I-HD while 45 transitioned to TW-HD after a mean duration of 9.8 ± 9.1 months. Patients who stayed on I-HD were less frequently diabetics (P = .007). Mean follow-up was 33.1 ± 30.8 months during which 124 (39.6%) patients died. Compared with patients on TW-HD, those on I-HD had improved survival (hazard ratio 0.49, 95% confidence interval 0.26-0.93, P = .029), while those on PD had similar survival. Initial kidney replacement therapy modality was not significantly associated with hospitalization days at 1 year. Conclusions I-HD is suitable for selected patients starting dialysis and can be maintained for a significant amount of time before transition to TW-HD, with diabetes being a risk factor. Although hospitalization days at 1 year are similar, initiation with I-HD is associated with improved survival as compared with TW-HD or PD. Results of randomized controlled trials are awaited prior to large-scale implementation of I-HD programmes. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Comparative efficacy of patiromer and sodium polystyrene sulfonate on potassium levels in chronic haemodialysis patients: a randomized crossover trial.
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Jaques, David A, Stucker, Fabien, Ernandez, Thomas, Alves, Cyrielle, Martin, Pierre-Yves, Seigneux, Sophie De, and Saudan, Patrick
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HEMODIALYSIS patients ,CROSSOVER trials ,HYPERKALEMIA ,POLYSTYRENE ,POTASSIUM ,SODIUM - Abstract
Background Hyperkalaemia is frequent in haemodialysis (HD) patients and associated with increased cardiovascular mortality. Despite routine clinical use, evidence regarding the efficacy of potassium (K
+ ) binders in HD is scant. We wished to compare the efficacy of patiromer (PAT) and sodium polystyrene sulfonate (SPS) on K+ levels in this setting. Methods We screened patients in three HD centres with pre-HD K+ value between 5.0 and 6.4 mmol/L, after an initial 2-week washout period for those previously on K+ binders. We included patients in an unblinded two-arm crossover trial comparing SPS 15 g before each meal on non-dialysis days with PAT 16.8 g once daily on non-dialysis days with randomized attribution order and a 2-week intermediate washout period. The primary outcome was the mean weekly K+ value. Results We included 51 patients and analysed 48 with mean age of 66.4 ± 19.4 years, 72.9% men and 43.4% diabetics. Mean weekly K+ values were 5.00 ± 0.54 mmol/L, 4.55 ± 0.75 mmol/L and 5.17 ± 0.64 mmol/L under PAT (P = .003), SPS (P < .001) and washout, respectively. In direct comparison, K+ values and prevalence of hyperkalaemia were lower under SPS as compared with PAT (P < .001). While the incidence of gastrointestinal side effects was similar between treatments, SPS showed lower subjective tolerability score (6.0 ± 2.4 and 6.9 ± 1.9) and compliance (10.8 ± 20.4% and 2.4 ± 7.3% missed doses) as compared with PAT (P < .001 for both). Conclusion Both PAT and SPS are effective in decreasing K+ levels in chronic HD patients. However, at the tested doses, SPS was significantly more effective in doing so as compared with PAT, despite lower tolerability and compliance. Larger randomized controlled trials should be conducted in order to confirm our findings and determine whether they would impact clinical outcomes. [ABSTRACT FROM AUTHOR]- Published
- 2022
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10. Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism.
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Legouis, David, Faivre, Anna, Cippà, Pietro E, and Seigneux, Sophie de
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GLUCONEOGENESIS ,GLUCOSE metabolism ,PROXIMAL kidney tubules ,HUMAN biology ,ACUTE kidney failure - Abstract
Glucose levels are tightly regulated at all times. Gluconeogenesis is the metabolic pathway dedicated to glucose synthesis from non-hexose precursors. Gluconeogenesis is critical for glucose homoeostasis, particularly during fasting or stress conditions. The renal contribution to systemic gluconeogenesis is increasingly recognized. During the post-absorptive phase, the kidney accounts for ∼40% of endogenous gluconeogenesis, occurring mainly in the kidney proximal tubule. The main substrate for renal gluconeogenesis is lactate and the process is regulated by insulin and cellular glucose levels, but also by acidosis and stress hormones. The kidney thus plays an important role in the maintenance of glucose and lactate homoeostasis during stress conditions. The impact of acute and chronic kidney disease and proximal tubular injury on gluconeogenesis is not well studied. Recent evidence shows that in both experimental and clinical acute kidney injury, impaired renal gluconeogenesis could significantly participate in systemic metabolic disturbance and thus alter the prognosis. This review summarizes the biochemistry of gluconeogenesis, the current knowledge of kidney gluconeogenesis, its modifications in kidney disease and the clinical relevance of this fundamental biological process in human biology. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Increased expression but not targeting of ENaC in adrenalectomized rats with PAN-induced nephrotic syndrome
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Seigneux, Sophie de, Kim, Soo Wan, Hemmingsen, Sophie C., Frokiaer, Jorgen, and Nielsen, Soren
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Nephrotic syndrome -- Research ,Sodium channels -- Research ,Vasopressin -- Research ,Biological sciences - Abstract
Sodium retention is a hallmark of nephrotic syndrome (NS). Puromycin aminonucleoside (PAN)-induced NS is associated with high aldostetone levels and increased ENaC expression and apical targeting. However, the mechanisms associated with increased apical targeting of ENaC in NS remain undefined, and it is unclear whether this is secondary to high aldosterone levels and whether aldosterone and/or apical ENaC targeting are important for the development of sodium retention. This study aimed at uncovering 1) whether aldosterone is essential for sodium retention in PAN-induced NS, 2) whether ENaC expression or apical targeting is secondary to high aldosterone levels, and 3) the role of aldosterone in the dysregulation of sodium transporters in NS. Puromycin treatment of adrenalectomized (ADX) rats supplemented with dexamethasone induced sodium retention despite the absence of aldosterone. Immunocytochemical analyses revealed an absence of enhanced apical targeting of ENaC subunits in PANtreated ADX (ADX-PAN) rats, with distribution of labeling similar to adrenalectomized dexamethasone-treated control rats (ADX). Moreover, ENaC subunit abundance was increased in ADX-PAN rats. The abundance of aquaporin-2 was unchanged, whereas apical targeting was enhanced. Key sodium transporters were downregulated as previously observed in nonadrenalectomized puromycin-treated rats (Kim SW, Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frokiaer J, and Nielsen S. Am J Physiol Renal Physiol 286: F922-F935, 2004), whereas the global expression of the [[alpha].sub.l]-subunit of the Na-K-ATPase was unchanged. In conclusion, PAN treatment in the absence of aldosterone induced sodium retention, increased ENaC expression, but did not change the subcellular distribution of ENaC. This indicates that the previously observed enhanced apical targeting of ENaC in PAN-induced NS (Kim SW, Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frokiaer J, and Nielsen S. Am J Physiol Renal Physiol 286: F922-F935, 2004) is caused by aldosterone and that development of sodium retention can occur in the absence of aldosterone in NS. epithelial sodium channel; sodium retention; aldosterone; AQP2; vasopressin
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- 2006
12. Dietary sodium intake does not alter renal potassium handling and blood pressure in healthy young males.
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Pechère-Bertschi, Antoinette, Olivier, Valérie, Burnier, Michel, Udwan, Khalil, Seigneux, Sophie de, Ponte, Belén, Maillard, Marc, Martin, Pierre-Yves, and Feraille, Eric
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DIETARY sodium ,HIGH-salt diet ,BLOOD pressure ,FOOD consumption ,POTASSIUM - Abstract
Background The effects of sodium (Na
+ ) intakes on renal handling of potassium (K+ ) are insufficiently studied. Methods We assessed the effect of Na+ on renal K+ handling in 16 healthy males assigned to three 7-day periods on low salt diet [LSD, 3 g sodium chloride (NaCl)/day], normal salt diet (NSD, 6 g NaCl/day) and high salt diet (HSD, 15 g NaCl/day), with constant K+ intake. Contributions of distal NaCl co-transporter and epithelial Na+ channel in the collecting system on K+ and Na+ handling were assessed at steady state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively. Results Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 mL/min under LSD to 187.00 ± 49.10 under HSD (P = 0.005). The 24-h K+ excretion remained stable on all Na+ intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD; and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h) and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all three diets. Conclusions Neither spontaneous nor diuretic-induced K+ excretion was influenced by Na+ intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal Na+ handling was dependent on dietary Na+ intake. [ABSTRACT FROM AUTHOR]- Published
- 2022
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13. Hypoxia in chronic kidney disease: towards a paradigm shift?
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Faivre, Anna, Scholz, Carsten C., and Seigneux, Sophie de
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HYPOXEMIA ,CHRONIC kidney failure ,HYDROXYLASE inhibitors ,MEDICAL care costs ,HYPOXIA-inducible factors ,DISEASE progression ,FIBROSIS - Abstract
Chronic kidney disease (CKD) is defined as an alteration of kidney structure and/or function lasting for >3 months [ 1 ]. CKD affects 10% of the general adult population and is responsible for large healthcare costs [ 2 ]. Since the end of the last century, the role of hypoxia in CKD progression has controversially been discussed. To date, there is evidence of the presence of hypoxia in late-stage renal disease, but we lack time-course evidence, stage correlation and also spatial co-localization with fibrotic lesions to ensure its causative role. The classical view of hypoxia in CKD progression is that it is caused by peritubular capillary alterations, renal anaemia and increased oxygen consumption regardless of the primary injury. In this classical view, hypoxia is assumed to further induce pro-fibrotic and pro-inflammatory responses, as well as oxidative stress, leading to CKD worsening as part of a vicious circle. However, recent investigations tend to question this paradigm, and both the presence of hypoxia and its role in CKD progression are still not clearly demonstrated. Hypoxia-inducible factor (HIF) is the main transcriptional regulator of the hypoxia response. Genetic HIF modulation leads to variable effects on CKD progression in different murine models. In contrast, pharmacological modulation of the HIF pathway [i.e. by HIF hydroxylase inhibitors (HIs)] appears to be generally protective against fibrosis progression experimentally. We here review the existing literature on the role of hypoxia, the HIF pathway and HIF HIs in CKD progression and summarize the evidence that supports or rejects the hypoxia hypothesis, respectively. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease.
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Faivre, Anna, Katsyuba, Elena, Verissimo, Thomas, Lindenmeyer, Maja, Rajaram, Renuga Devi, Naesens, Maarten, Heckenmeyer, Carolyn, Mottis, Adrienne, Feraille, Eric, Cippà, Pietro, Cohen, Clemens, Longchamp, Alban, Allagnat, Florent, Rutkowski, Joseph M, Legouis, David, Auwerx, Johan, and Seigneux, Sophie de
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CHRONIC kidney failure ,VITAMIN B deficiency ,NICOTINAMIDE ,RENAL biopsy ,RNA sequencing ,INTESTINAL ischemia - Abstract
Background Nicotinamide adenine dinucleotide (NAD
+ ) is a ubiquitous coenzyme involved in electron transport and a co-substrate for sirtuin function. NAD+ deficiency has been demonstrated in the context of acute kidney injury (AKI). Methods We studied the expression of key NAD+ biosynthesis enzymes in kidney biopsies from human allograft patients and patients with chronic kidney disease (CKD) at different stages. We used ischaemia–reperfusion injury (IRI) and cisplatin injection to model AKI, urinary tract obstruction [unilateral ureteral obstruction (UUO)] and tubulointerstitial fibrosis induced by proteinuria to investigate CKD in mice. We assessed the effect of nicotinamide riboside (NR) supplementation on AKI and CKD in animal models. Results RNA sequencing analysis of human kidney allograft biopsies during the reperfusion phase showed that the NAD+ de novo synthesis is impaired in the immediate post-transplantation period, whereas the salvage pathway is stimulated. This decrease in de novo NAD+ synthesis was confirmed in two mouse models of IRI where NR supplementation prevented plasma urea and creatinine elevation and tubular injury. In human biopsies from CKD patients, the NAD+ de novo synthesis pathway was impaired according to CKD stage, with better preservation of the salvage pathway. Similar alterations in gene expression were observed in mice with UUO or chronic proteinuric glomerular disease. NR supplementation did not prevent CKD progression, in contrast to its efficacy in AKI. Conclusion Impairment of NAD+ synthesis is a hallmark of AKI and CKD. NR supplementation is beneficial in ischaemic AKI but not in CKD models. [ABSTRACT FROM AUTHOR]- Published
- 2021
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15. Validation of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for kidney fibrosis detection: a cross-sectional study.
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Berchtold, Lena, Friedli, Iris, Crowe, Lindsey A, Martinez, Chantal, Moll, Solange, Hadaya, Karine, Perrot, Thomas de, Combescure, Christophe, Martin, Pierre-Yves, Vallée, Jean-Paul, and Seigneux, Sophie de
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RENAL fibrosis ,DIFFUSION magnetic resonance imaging ,DIFFUSION coefficients ,MAGNETIC resonance ,CROSS-sectional method - Abstract
Background Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. Methods This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. Results Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r =−0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. Conclusion ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF. [ABSTRACT FROM AUTHOR]
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- 2020
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16. The KNOW-CKD study: evidence for a link between proteinuria and alterations of mineral metabolism.
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Seigneux, Sophie de, Delitsikou, Vasiliki, and Martin, Pierre-Yves
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RENAL fibrosis , *METABOLISM , *FIBROBLAST growth factors , *HYPERPHOSPHATEMIA , *CHRONIC kidney failure , *CHINESE people - Published
- 2020
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17. Contribution of Genetic Background and Data Collection on Adverse Events of Anti–human Immunodeficiency Virus (HIV) Drugs (D:A:D) Clinical Risk Score to Chronic Kidney Disease in Swiss HIV-infected Persons With Normal Baseline Estimated Glomerular Filtration Rate
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Dietrich, Léna G, Barceló, Catalina, Thorball, Christian W, Ryom, Lene, Burkhalter, Felix, Hasse, Barbara, Furrer, Hansjakob, Weisser, Maja, Steffen, Ana, Bernasconi, Enos, Cavassini, Matthias, Seigneux, Sophie de, Csajka, Chantal, Fellay, Jacques, Ledergerber, Bruno, and Tarr, Philip E
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HIV infection genetics ,CHRONIC kidney failure ,CONFIDENCE intervals ,DRUG side effects ,GENETIC polymorphisms ,GENETIC techniques ,GLOMERULAR filtration rate ,HIV-positive persons ,HUMAN genome ,LONGITUDINAL method ,MULTIVARIATE analysis ,RISK assessment ,STATISTICS ,WHITE people ,HIGHLY active antiretroviral therapy ,ACQUISITION of data ,CASE-control method ,ANTI-HIV agents ,DESCRIPTIVE statistics ,ODDS ratio ,GENOTYPES ,DISEASE risk factors - Abstract
Background In human immunodeficiency virus (HIV), the relative contribution of genetic background, clinical risk factors, and antiretrovirals to chronic kidney disease (CKD) is unknown. Methods We applied a case-control design and performed genome-wide genotyping in white Swiss HIV Cohort participants with normal baseline estimated glomerular filtration rate (eGFR >90 mL/minute/1.73 m
2 ). Univariable and multivariable CKD odds ratios (ORs) were calculated based on the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) score, which summarizes clinical CKD risk factors, and a polygenic risk score that summarizes genetic information from 86 613 single-nucleotide polymorphisms. Results We included 743 cases with confirmed eGFR drop to <60 mL/minute/1.73 m2 (n = 144) or ≥25% eGFR drop to <90 mL/minute/1.73 m2 (n = 599), and 322 controls (eGFR drop <15%). Polygenic risk score and D:A:D score contributed to CKD. In multivariable analysis, CKD ORs were 2.13 (95% confidence interval [CI], 1.55–2.97) in participants in the fourth (most unfavorable) vs first (most favorable) genetic score quartile; 1.94 (95% CI, 1.37–2.65) in the fourth vs first D:A:D score quartile; and 2.98 (95% CI, 2.02–4.66), 1.70 (95% CI, 1.29–2.29), and 1.83 (95% CI, 1.45–2.40), per 5 years of exposure to atazanavir/ritonavir, lopinavir/ritonavir, and tenofovir disoproxil fumarate, respectively. Participants in the first genetic score quartile had no increased CKD risk, even if they were in the fourth D:A:D score quartile. Conclusions Genetic score increased CKD risk similar to clinical D:A:D score and potentially nephrotoxic antiretrovirals. Irrespective of D:A:D score, individuals with the most favorable genetic background may be protected against CKD. [ABSTRACT FROM AUTHOR]- Published
- 2020
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18. Potential benefits and harms of NADPH oxidase type 4 in the kidneys and cardiovascular system.
- Author
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Rajaram, Renuga D, Dissard, Romain, Jaquet, Vincent, and Seigneux, Sophie de
- Subjects
NADPH oxidase ,CARDIOVASCULAR system ,SUPEROXIDES ,OXIDASES ,VASCULAR endothelial cells ,VASCULAR smooth muscle ,MUSCLE cells - Abstract
The main function of NADPH oxidases is to catalyse the formation of reactive oxygen species (ROS). NADPH oxidase 4 (NOX4) is expressed at high levels in kidney tubular cells, and at lower levels in endothelial cells, cardiomyocytes and other cell types under physiological conditions. NOX4 is constitutively active producing hydrogen peroxide (H
2 O2 ) as the prevalent ROS detected, whereas other NOX isoforms present in the renal and cardiovascular systems (i.e. NOX1, NOX2 and NOX5) generate superoxide radical anions as main products. Pharmacological inhibition of NOX4 has received enormous attention for its potential therapeutic benefit in fibrotic disease and nephropathologies. Ongoing clinical trials are testing this approach in humans. Diabetes elevates NOX4 expression in podocytes and mesangial cells, which was shown to damage glomeruli leading to podocyte loss, mesangial cell hypertrophy and matrix accumulation. Consequently, NOX4 represents an interesting therapeutic target in diabetic nephropathy. On the contrary, experiments using NOX4-deficient mice have shown that NOX4 is cytoprotective in tubular cells, cardiomyocytes, endothelial cells and vascular smooth muscle cells, and has a metabolism-regulating role when these cells are subjected to injury. Mice with systemic NOX4 deletion are more susceptible to acute and chronic tubular injury, heart failure and atherosclerosis. Overall, the current literature suggests a detrimental role of increased NOX4 expression in mesangial cells and podocytes during diabetic nephropathy, but a cytoprotective role of this enzyme in other cellular types where it is expressed endogenously. We review here the recent evidence on the role of NOX4 in the kidneys and cardiovascular system. With the emergence of pharmacological NOX4 inhibitors in clinical trials, caution should be taken in identifying potential side effects in patients prone to acute kidney injury and cardiovascular disease. [ABSTRACT FROM AUTHOR]- Published
- 2019
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19. Diffusion magnetic resonance imaging detects an increase in interstitial fibrosis earlier than the decline of renal function.
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Berchtold, Lena, Crowe, Lindsey A, Friedli, Iris, Legouis, David, Moll, Solange, Perrot, Thomas de, Martin, Pierre-Yves, Vallée, Jean-Paul, and Seigneux, Sophie de
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DIFFUSION magnetic resonance imaging ,DIABETIC nephropathies ,FIBROSIS ,INTERSTITIAL nephritis - Published
- 2020
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20. Renal injury and human immunodeficiency virus: what remains after 30 years?
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Seigneux, Sophie de and Lucas, Gregory M
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- *
HIV , *RENAL tubular transport disorders , *KIDNEY glomerulus diseases , *HIGHLY active antiretroviral therapy , *WOUNDS & injuries - Published
- 2020
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21. AQP2 and renal sodium transporters in endotoxemia: Segmental dysregulation and relation to activated macrophages
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Olesen, Emma T.B., Seigneux, Sophie de, Wang, Guixian, Kwon, Tae-Hwan, Frøkiær, Jørgen, and Nielsen, Søren
- Published
- 2008
22. Increased Apical Targetin of Renal ENaC Subunits and Decreased Expression of 11βHSD2 in HgCI2-induced Nephrotic Syndrome in Rats
- Author
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Kim, SW, Seigneux, Sophie de, Sassen, Martin Christian, Knepper, Mark A, and Frøkiær, Jørgen
- Abstract
Udgivelsesdato: Marts
- Published
- 2006
23. Haemoglobin as a marker of fibrosis in early diabetic kidney disease.
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Faivre, Anna and Seigneux, Sophie de
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- *
HEMOGLOBINS , *FIBROSIS , *DIABETIC nephropathies , *RENAL fibrosis , *TYPE 2 diabetes - Published
- 2022
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24. Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor.
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Dizin, Eva, Hasler, Udo, Nlandu-Khodo, Stellor, Fila, Marc, Roth, Isabelle, Ernandez, Thomas, Doucet, Alain, Martin, Pierre-Yves, Feraille, Eric, and Seigneux, Sophie de
- Subjects
ALBUMINURIA ,KIDNEY diseases ,INTERSTITIAL nephritis ,IMMUNOFLUORESCENCE ,FIBROSIS ,PROTEINURIA ,THERAPEUTICS - Abstract
Albuminuria is strongly associated with progressive kidney tubulointerstitial damage and chronic kidney disease (CKD) progression. In proteinuric nephropathies, albumin reabsorption by the proximal tubule is saturated and the distal nephron is exposed to high concentrations of luminal albumin that may produce adverse effects. Since proximal tubular cells exposed to albuminuria exhibit a proinflammatory and profibrotic response, we assessed the effect of albuminuria in the collecting duct (CD). With the use of kidney sections and isolated cortical CDs (CCDs) from puromycin-aminonucleoside-induced nephrotic rats (PAN rats) exhibiting proteinuria, immunofluorescence microscopy revealed internalized albumin in CD cells. In these proteinuric rats, increased expression levels of cytokines and profibrotic signaling markers were detected in isolated CCDs and bands of inflammatory fibrosis could be observed around CDs. Albumin endocytosis was confirmed by FITC-albumin uptake in cultured murine CCD (mCCDcl1) cells. Exposure of mCCDcl1 cells to albumin induced NF-κB activation as assessed by luciferase reporter gene assay, nuclear translocation of NF-κB p65 subunit, and increased NF-κB target gene expression. Moreover, albuminuria-like condition results in transforming growth factor-β
1 (TGF-β1 ) overexpression and the upregulation of profibrotic signaling markers such as Snail or vimentin via an autocrine mechanism. In mCCDcl1 cells, neutrophil gelatinase- associated lipocalin (NGAL)/lipocalin-2/24p3 receptor (24p3R) mediates albumin endocytosis as well as activation of NF-κB and TGF-β1 signaling pathways. Therefore, CD may play a key role in initiation and/or progression of inflammation and fibrosis in response to proteinuria. [ABSTRACT FROM AUTHOR]- Published
- 2013
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25. NF-κB Inhibits Sodium Transport via Down-regulation of SGK1 in Renal Collecting Duct Principal Cells.
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Seigneux, Sophie de, Leroy, Valerie, GhziIi, Hafida, Rousselot, Martine, Nielsen, Søren, Rossier, Bernard C., Martin, Pierre-Yves, and Féraille, Eric
- Subjects
- *
SODIUM , *CELLS , *KIDNEYS , *INFLAMMATION , *ENDOTOXINS - Abstract
Tubulointerstitial inflammation is a common feature of renal diseases. We have investigated the relationship between inflammation and Na+ transport in the collecting duct (CD) using the mCCDcl1 and mpkCDDcl4 principal cell models. Lipopolysaccharide (LPS) decreased basal and aldosterone-stimulated amiloride-sensitive transepithelial current in a time-dependent manner. This effect was associated with a decrease in serum and gucocorticoid-regulated kinase 1 (SGK1) mRNA and protein levels followed by a decrease in epithelial sodium channel (ENaC) α-subunit mRNA levels. The LPS-induced decrease in SGK1 expression was confirmed in isolated rat CD. This decreased expression of either SGK1 or the ENaC α-subunit was not due to enhanced degradation of mRNA. In contrast, LPS inhibited transcriptional activity of the SGK1 promoter measured by luciferase-reporter gene assay. The effect of LPS was not mediated by inhibition of mineralocorticoid or glucocorticoid receptor, because expression of both receptors was unchanged and blockade of either receptor by spironolactone or RU486, respectively, did not prevent the down-regulation of SGK1. The effect of LPS was mediated by the canonical NF-κB pathway, as overexpression of a constitutively active mutant, IKKβ (inhibitor of nuclear factor κB kinase-β) decreased SGK1 mRNA levels, and knockdown of p65 NF-κB subunit by small interfering RNA increased SGK1 mRNA levels. Chromatin immunoprecipitation showed that LPS increased p65 binding to two NF-κB sites along the SGK1 promoter. In conclusion, we show that activation of the NF-κB pathway down-regulates SGK1 expression, which might lead to decreased ENaC α-subunit expression, ultimately resulting in decreased Na+ transport. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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26. Diffusion-weighted magnetic resonance imaging to assess diffuse renal pathology: a systematic review and statement paper.
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Caroli, Anna, Schneider, Moritz, Friedli, Iris, Ljimani, Alexandra, Seigneux, Sophie De, Boor, Peter, Gullapudi, Latha, Kazmi, Isma, Mendichovszky, Iosif A, and Notohamiprodjo, Mike
- Subjects
DIFFUSION magnetic resonance imaging ,KIDNEY diseases ,BIOLOGICAL tags ,FIBROSIS ,ANISOTROPY - Abstract
Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive method sensitive to local water motion in the tissue. As a tool to probe the microstructure, including the presence and potentially the degree of renal fibrosis, DWI has the potential to become an effective imaging biomarker. The aim of this review is to discuss the current status of renal DWI in diffuse renal diseases. DWI biomarkers can be classified in the following three main categories: (i) the apparent diffusion coefficient—an overall measure of water diffusion and microcirculation in the tissue; (ii) true diffusion, pseudodiffusion and flowing fraction—providing separate information on diffusion and perfusion or tubular flow; and (iii) fractional anisotropy—measuring the microstructural orientation. An overview of human studies applying renal DWI in diffuse pathologies is given, demonstrating not only the feasibility and intra-study reproducibility of DWI but also highlighting the need for standardization of methods, additional validation and qualification. The current and future role of renal DWI in clinical practice is reviewed, emphasizing its potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease, as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. As part of the international COST (European Cooperation in Science and Technology) action PARENCHIMA (Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease), aimed at eliminating the barriers to the clinical use of functional renal magnetic resonance imaging, this article provides practical recommendations for future design of clinical studies and the use of renal DWI in clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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