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Background: In the last 2 decades, new technologies have emerged in health care. The COVID-19 pandemic further accelerated the adoption of technology by both health care professionals and patients. These technologies create remote care practices that bring several benefits to the health care system: easier access to care, improved communication with physicians, and greater continuity of care. However, disparities in the acceptance and use of telehealth tools still exist among patients. These tools also disrupt conventional medical practices and prompt a new reassessment of the perceptions of distance and proximity as physical (ie, time and space dimensions) and nonphysical (ie, behavioral dimensions) concepts. The reasons why patients do or do not adopt telehealth tools for their care and therefore their perspectives on telehealth remain unanswered questions., Objective: We explored the barriers as well as the motivations for patients to adopt telehealth tools. We specifically focused on the social representations of telehealth to establish a comprehensive conceptual framework to get a better understanding of how telehealth is perceived by patients., Methods: This study uses a qualitative design through in-depth individual interviews. Participants were recruited using a convenience sampling method with balanced consideration of gender, age, location (urban/rural), and socioeconomic background. After collecting informed consent, interviews were transcribed and analyzed using the thematic analysis methodology., Results: We conducted 14 interviews, with which data saturation was reached. The 2 main opposed dimensions, perceived proximity and distance, emerged as an essential structure for understanding the social representations of telehealth. A logic of engagement versus hostility emerged as the main tension in adopting telehealth, almost ideological. Interestingly, practical issues emerged regarding the adoption of telehealth: A logic of integration was opposed to a logic of constraints. Altogether, those dimensions enabled us to conceptualize a semiotic square, providing 4 categories with a coherent body of social representations. Due to the dynamic nature of these representations, we proposed 2 "paths" through which adherence to telehealth may improve., Conclusions: Our semiotic square illustrating patients' adherence to telehealth differentiates socially beneficial versus socially dangerous considerations and pragmatic from ideological postures. It shows how crucial it is to consider perceived distance and proximity to better understand barriers and motivations to adopting telehealth. These representations can also be considered as leverage that could be modified to encourage the step-by-step adhesion process. Even if reducing the perceived temporal distance to in-person meeting and enhancing the perceived proximity of access to care may be seen as efficient ways to adopt telehealth tools, telehealth can also be perceived as a care practice that threatens the patient-physician relationship. The patient-oriented perceived value turns out to be critical in the future development of and adherence to telehealth tools., (©Amélie Loriot, Fabrice Larceneux, Valérie Guillard, Jean-Philippe Bertocchio. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.04.2024.)

Background: Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum-based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum-based chemotherapy in RMC., Methods: We evaluated the IC 50 concentrations of the neddylation-activating enzyme inhibitor pevonedistat in vitro in RMC cell lines. Bliss synergy scores were calculated using growth inhibition assays following treatment with varying concentrations of pevonedistat and carboplatin. Protein expression was assessed by western blot and immunofluorescence assays. The efficacy of pevonedistat alone or in combination with platinum-based chemotherapy was evaluated in vivo in platinum-naïve and platinum-experienced patient-derived xenograft (PDX) models of RMC., Results: The RMC cell lines demonstrated IC 50 concentrations of pevonedistat below the maximum tolerated dose in humans. When combined with carboplatin, pevonedistat demonstrated a significant in vitro synergistic effect. Treatment with carboplatin alone increased nuclear ERCC1 levels used to repair the interstrand crosslinks induced by platinum salts. Conversely, the addition of pevonedistat to carboplatin led to p53 upregulation resulting in FANCD2 suppression and reduced nuclear ERCC1 levels. The addition of pevonedistat to platinum-based chemotherapy significantly inhibited tumour growth in both platinum-naïve and platinum-experienced PDX models of RMC (p < .01)., Conclusions: Our results suggest that pevonedistat synergises with carboplatin to inhibit RMC cell and tumour growth through inhibition of DNA damage repair. These findings support the development of a clinical trial combining pevonedistat with platinum-based chemotherapy for RMC., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Tacrolimus (Tac) is a calcineurin inhibitor commonly used as an immunosuppressor after solid organ transplantation. However, Tac may induce hypertension, nephrotoxicity, and an increase in aldosterone levels. The activation of the mineralocorticoid receptor (MR) is related to the proinflammatory status at the renal level. It modulates the vasoactive response as they are expressed on vascular smooth muscle cells (SMC). In this study, we investigated whether MR is involved in the renal damage generated by Tac and if the MR expressed in SMC is involved. Littermate control mice and mice with targeted deletion of the MR in SMC (SMC-MR-KO) were administered Tac (10 mg/Kg/d) for 10 days. Tac increased the blood pressure, plasma creatinine, expression of the renal induction of the interleukin (IL)-6 mRNA, and expression of neutrophil gelatinase-associated lipocalin (NGAL) protein, a marker of tubular damage ( p < 0.05). Our study revealed that co-administration of spironolactone, an MR antagonist, or the absence of MR in SMC-MR-KO mice mitigated most of the unwanted effects of Tac. These results enhance our understanding of the involvement of MR in SMC during the adverse reactions of Tac treatment. Our findings provided an opportunity to design future studies considering the MR antagonism in transplanted subjects.

Hypercalciuria is the main risk factor for recurrent calcium urolithiasis. The goal of our study is to determinate how useful an oral calcium load test is for stone formers to classify different forms of hypercalciuria in pathogenetic categories defined as renal or absorptive according to the current knowledge. Between June 2013 and February 2016, a prospective study was carried out on 117 documented recurrent hypercalciuric stone formers undergoing an oral calcium load test modified from the original description by Pak. After 2 days of calcium-restricted diet, urine and blood were analyzed at baseline and 120 min after receiving orally 1 g of calcium. Total and ionized calcium, parathyroid hormone from serum and urine calcium and creatinine were assessed in order to divide patients in three groups as previously described: resorptive, absorptive, and renal hypercalciuria. This allowed the identification of 19, 39, 34 and 33 patients with normocalcemic primary hyperparathyroidism (NPHPT), renal hypercalciuria aka renal calcium leak (RCL), absorptive hypercalciuria (AH) and unidentified cause, respectively. Patients with NPHPT (who required parathyroidectomy) experienced a lower PTH decrease (41.41 ± 12.82 vs. 54.06 ± 13.84% p < 0.01), higher beta-crosslaps, as well as lower TmP/GFR and distal third radius bone mineral density. RCL resulted in increased fasting urine calcium-to-creatinine ratio (Uca/Cr), i.e., > 0.37 mmol/mmol), without hyperparathyroidism. AH was diagnosed by the presence of ΔUCa/Cr > 0.60 mmol/mmol between baseline and 120 min without any other anomaly. For all remaining patients, results were inconclusive due to the lack of sufficient increase in serum calcium or because the cause of lithogenesis could not be clearly identified. The oral calcium load test is useful in nearly 80% of patients by identifying the different forms of hypercalciuria causing urolithiasis and by guiding treatment, including parathyroid surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD., Methods: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement., Results: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient., Conclusion: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients., Competing Interests: Conflict of interest L Guillo declares consulting fees for Abbvie. A Amiot declares counseling, boards, lecture, transports or fees from Abbvie, Hospira, Takeda, Gilead, Biocodex, Janssen, Ferring and MSD. B Caron has received lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Janssen, Takeda. G Boschetti has served as a speaker and advisory board member for Abbvie, Janssen, Ferring, Norgine, Tillotts, Pfizer, Celltrion, Takeda, Amgen, Sandoz. G Bouguen has received lecture fees from Abbvie, Ferring, MSD, Takeda, Otsuka, Amgen, Biogen, Celtrion, Janssen, Tillots and Pfizer and consultant fees from Takeda, Janssen, Mylan, Vifor Pharma and Gilead. JM Gornet has received personal fees from Amgen, Janssen Cilag, Sanofi, Takeda, Roche and Tillots Pharma. J Bonnet has received consulting fees for Amgen. L Vuitton has received lecture fees from Abbvie, MSD, Takeda, Ferring, Janssen and Pfizer, and research grants from MSD, Takeda and Pfizer. M Nachury received board membership, consultancy, or lecture fees from Abbvie, Adacyte, Amgen, Arena, CTMA, Celltrion, Ferring, Fresenius-Kabi, Janssen, Mayoli-Spindler, MSD, Pfizer, Takeda. M Uzzan has served as a speaker for Janssen and Abbvie. M Serrero declares lecture and consulting fees for Abbvie, Celltrion, Ferring, Janssen, MSD, Takeda and Tillotts. L Peyrin-Biroulet has served as a speaker, consultant and advisory board member for Merck, Abbvie, Janssen, Genentech, Mitsubishi, Ferring, Norgine, Tillotts, Vifor, Hospira/Pfizer, Celltrion, Takeda, Biogaran, Boerhinger-Ingelheim, Lilly, HAC- Pharma, Index Pharmaceuticals, Amgen, Sandoz, For- ward Pharma GmbH, Celgene, Biogen, Lycera, Samsung Bioepis, Theravance. The remaining authors declare no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Context: Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians' practices or their adherence to such guidelines., Objective: To describe the physicians' practice patterns and their compliance with international guidelines., Design: The cohort studies included were Épi-Hypo (118 physicians and 107 patients, from September 2016 to December 2019) and ePatients (110 patients, November 2019)., Methods: Internet-based cohorts involving all settings at a nationwide level (France). Participants were (i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the (ii) Épi-Hypo study (Épi-Hypo 2019 patients), or (iii) Hypoparathyroidism France, the national representative association (ePatients)., Results: The physicians' specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%), or miscellaneous (4%) and 45% were practicing in public universities. The median number of pharmaceutical drug classes prescribed was three per patient. The combination of active vitamin D and calcium salt was given to 59 and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32 and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion., Conclusions: The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target other specialists as well as endocrinologists. Full adherence to the guidelines is low in France.

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders (PARAT) in 2019, were discussed during two virtual workshops in 2021, and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosing to familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represent areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT, need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborns children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed for a broader clinical audience, and were developed with focus on endocrinologists in training.

Oral alkalization with sodium bicarbonate (NaHCO 3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO 3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO 3 -containing or no-NaHCO 3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO 3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO 3 is no longer associated with an ECV increase compared to citrate in real-life settings., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Renal medullary carcinoma (RMC) is a lethal malignancy affecting individuals with sickle hemoglobinopathies. Currently, no modifiable risk factors are known. We aimed to determine whether high-intensity exercise is a risk factor for RMC in individuals with sickle cell trait (SCT). We used multiple approaches to triangulate our conclusion. First, a case-control study was conducted at a single tertiary-care facility. Consecutive patients with RMC were compared to matched controls with similarly advanced genitourinary malignancies in a 1:2 ratio and compared on rates of physical activity and anthropometric measures, including skeletal muscle surface area. Next, we compared the rate of military service among our RMC patients to a similarly aged population of black individuals with SCT in the U.S. Further, we used genetically engineered mouse models of SCT to study the impact of exercise on renal medullary hypoxia. Compared with matched controls, patients with RMC reported higher physical activity and had higher skeletal muscle surface area. A higher proportion of patients with RMC reported military service than expected compared to the similarly-aged population of black individuals with SCT. When exposed to high-intensity exercise, mice with SCT demonstrated significantly higher renal medulla hypoxia compared to wild-type controls. These data suggest high-intensity exercise is the first modifiable risk factor for RMC in individuals with SCT.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods : We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches., 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 © 2021 Bui, Prot-Bertoye, Ayari, Baron, Bertocchio, Bureau, Davis, Blanchard, Houillier, Prie, Lillo-Le Louet and Courbebaisse.)

Epigenetic effectors "read" marks "written" on chromatin to regulate function and fidelity of the genome. Here, we show that this coordinated read-write activity of the epigenetic machinery extends to the cytoskeleton, with PBRM1 in the PBAF chromatin remodeling complex reading microtubule methyl marks written by the SETD2 histone methyltransferase. PBRM1 binds SETD2 methyl marks via BAH domains, recruiting PBAF components to the mitotic spindle. This read-write activity was required for normal mitosis: Loss of SETD2 methylation or pathogenic BAH domain mutations disrupt PBRM1 microtubule binding and PBAF recruitment and cause genomic instability. These data reveal PBRM1 functions beyond chromatin remodeling with domains that allow it to integrate chromatin and cytoskeletal activity via its acetyl-binding BD and methyl-binding BAH domains, respectively. Conserved coordinated activity of the epigenetic machinery on the cytoskeleton opens a previously unknown window into how chromatin remodeler defects can drive disease via both epigenetic and cytoskeletal dysfunction., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Competing Interests: L’auteur déclare avoir participé à des interventions ponctuelles (activités de conseil et conférences) pour l’entreprise Shire ; et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Amgen, Fresenius Medical Care.

Competing Interests: L’auteur déclare avoir participé à des interventions ponctuelles (activités de conseil et conférences) pour l’entreprise Shire ; et avoir été pris en charge, à l’occasion de déplacements pour congrès, par Amgen, Fresenius Medical Care.

Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA-damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

2017 was the year during which France has seen the amendment of the 3rd cycle of medical education. Three new steps have been uploaded: "basement", "in depth", and "liability". The latter has been particularly discussed as it is really close to the former post-graduate state. Nephrology has always been a very attractive discipline. While most others have been increased in terms of length in initial medical education, nephrology has been assigned to 4 years. Altogether, nephrologists whatever their generation have led a series of questionnaires we report here. From 3 of them, we had new data providing insights regarding both their feeling and knowledge about this amendment. Globally, they dissatisfy whatever the considered generation and they propose different modifications. The upcoming generation especially wants more options and tailored initial formation when older nephrologists are more prone to require one additional year for all. Whatever is chosen by state institutions, representative associations such as SNIN, CJN, and CUEN should act together as spokeperson to disseminate both nephrologists' wishes and information about what is coming., (Copyright © 2019 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Anion exchanger 1 (AE1) ( SLC4A1 gene product) is a membrane protein expressed in both kidney and red blood cells (RBCs): it exchanges extracellular bicarbonate (HCO 3 - ) for intracellular chloride (Cl - ) and participates in acid-base homeostasis. AE1 mutations in kidney α-intercalated cells can lead to distal renal tubular acidosis (dRTA). In RBC, AE1 (known as band 3) is also implicated in membrane stability: deletions can cause South Asian ovalocytosis (SAO)., Methods: We retrospectively collected clinical and biological data from patients harboring dRTA due to a SLC4A1 mutation and analyzed HCO 3 - and Cl - transports (by stopped-flow spectrophotometry) and expression (by flow cytometry, fluorescence activated cell sorting, and Coomassie blue staining) in RBCs, as well as RBC membrane stability (ektacytometry)., Results: Fifteen patients were included. All experience nephrolithiasis and/or nephrocalcinosis, 2 had SAO and dRTA (dRTA SAO+), 13 dominant dRTA (dRTA SAO-). The latter did not exert specific RBC membrane anomalies. Both HCO 3 - and Cl - transports were lower in patients with dRTA SAO+ than in those with dRTA SAO- or controls. Using 3 different extracellular probes, we report a decreased expression (by 52%, P  < 0.05) in dRTA SAO+ patients by fluorescence activated cell sorting, whereas total amount of protein was not affected., Conclusion: Band 3 transport function and expression in RBCs from dRTA SAO- patients is normal. However, in SAO RBCs, impaired conformation of AE1/band 3 corresponds to an impaired function. Thus, the driver of acid-base defect during dominant dRTA is probably an impaired membrane expression., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background and Objectives: Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine., Design, Setting, Participants, & Measurements: Among 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m 2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µ Eq/min at one or more of the six time points after furosemide and fludrocortisone administration., Results: Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality ( r 2 =0.34, P =0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity., Conclusions: Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019&#95;12&#95;10&#95;CJN07830719.mp3., (Copyright © 2020 by the American Society of Nephrology.)

Background: Tributyltin (TBT) is a persistent and bioaccumulative environmental toxicant. Developmental exposure to TBT has been shown to cause fatty liver disease (steatosis), as well as increased adiposity in many species, leading to its characterization as an obesogen., Objective: We aimed to determine the long-term effects of developmental TBT exposure on the liver., Methods: C57BL/6J mice were exposed to a dose of TBT ( 0.5 mg / kg body weight per day; 3.07 μ M ) below the current developmental no observed adverse effect level (NOAEL) via drinking water, or drinking water alone, provided to the dam from preconception through lactation. Sires were exposed during breeding and lactation. Pups from two parity cycles were included in this study. Animals were followed longitudinally, and livers of offspring were analyzed by pathological evaluation, immunohistochemistry, immunoblotting, and RNA sequencing., Results: Developmental exposure to TBT led to increased adiposity and hepatic steatosis at 14 and 20 weeks of age and increased liver adenomas at 45 weeks of age in male offspring. Female offspring displayed increased adiposity as compared with males, but TBT did not lead to an increase in fatty liver or tumor development in female offspring. Liver tumors in male mice were enriched in pathways and gene signatures associated with human and rodent nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). This includes down-regulation of growth hormone receptor (GHR) and of STAT5 signaling, which occurred in response to TBT exposure and preceded liver tumor development., Conclusions: These data reveal a previously unappreciated ability of TBT to increase risk for liver tumorigenesis in mice in a sex-specific manner. Taken together, these findings provide new insights into how early life environmental exposures contribute to liver disease in adulthood. https://doi.org/10.1289/EHP5414.

The number of new patients with chronic kidney diseases strongly increases while the one of nephrologists does not: this is developing new challenges, in which e-health will take a special part. This field is poorly investigated: so, we developed a dedicated survey. Telenephrology is a new approach that includes all what nephrologists can do in their routine practice: especially, telehealth with teleconsulting, telesurvey, and helpline. We also studied their relationship with m-health. The questionnaire was developed and validated by members from the Club des Jeunes Néphrologues and the Société Francophone de Néphrologie, Dialyse et Transplantation: it was then broadcast to all french nephrologists, thru web media. From June to July, 2017, we collected 175 answers: they represented all kinds of practices of the profession. Results show that French nephrologists are connected: most of them are present on social network(s) and/or uses connected objects, mostly for personal reasons. They communicate a lot, between them and/or with patients, mainly via email. Computerized medical records are mostly used in the follow-up of patients on renal dialysis or with chronic kidney diseases. Most of French nephrologists are satisfied by telenephrology but there are still obstacles to its deployment: mainly, technical, administrative, and/or billing difficulties. All should be taken into account to help telenephrology developing. In conclusion, French nephrologists are yet connected but they really need more help again to face new challenges raised by e-health., (Copyright © 2019. Published by Elsevier Masson SAS.)

Fabry disease is a systemic and genetic disorder resulting from an α-galactosidase A enzymatic deficiency leading to sphingolipid accumulation in lysosomes: it remains a rare and poorly-known disease. This study aimed to know the formation of nephrologists, their knowledge, and their habits both in terms of screening and management in this field. Answers form 152 nephrologists have been analyzed: few doctors directly managed Fabry disease patient (22 %) and 18 % have already made the diagnosis by their own. Formation seems to be insufficient and most of them did not fully know symptoms, as resources already available (associations, collecting database, etc.). Some indications for the treatment are also poorly known (mainly regarding end stage renal disease). Information is mainly provided by of firms' staff. A knowledge score was calculated: the kidney injury is also poorly known (less than 50 % of correct answers) even if 50 % of nephrologists performed appropriate testing and confirmation, around 65 % knew the symptoms, treatment indication and the main key points of the disease. Fabry disease is still an unknown disorder, unless early diagnosis tools and therapeutics exist to reduce its complications. Nephrology community has to invest more formation about symptoms, testing, and medical care., (Copyright © 2019 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Context: Parathyroid-related hypercalcemia is due to primary hyperparathyroidism (PHPT) or to familial hypocalciuric hypercalcemia (FHH). PHPT can lead to complications that necessitate parathyroidectomy. FHH is a rare genetic disease resembling PHPT; surgery is ineffective. A reliable method for distinguishing FHH from PHPT is needed., Objective: To develop an easy-to-use tool to predict if a patient has PHPT., Design: Retrospective analysis of two prospective cohorts. Development of an unsupervised risk equation (Pro-FHH)., Setting: University hospitals in Paris, France, and Aarhus, Denmark., Participants: Patients (Paris: 65 with FHH, 85 with PHPT; Aarhus: 38 with FHH, 55 with PHPT) were adults with hypercalcemia and PTH concentration within normal range., Main Outcome Measures: Performance of Pro-FHH to predict PHPT., Results: Pro-FHH takes into account plasma calcium, PTH, and serum osteocalcin concentrations, and calcium-to-creatinine clearance ratio calculated from 24-hour urine collection (24h-CCCR). In the Paris cohort, area under the receiver operating characteristic curve (AUROC) of Pro-FHH was 0.961, higher than that of 24h-CCCR. With a cutoff value of 0.928, Pro-FHH had 100% specificity and 100% positive predictive value for the diagnosis of PHPT; it correctly categorized 51 of 85 patients with PHPT; the remaining 34 were recommended to undergo genetic testing. No patients with FHH were wrongly categorized. In an independent cohort from Aarhus, AUROC of Pro-FHH was 0.951, higher than that of 24h-CCCR., Conclusion: Pro-FHH effectively predicted whether a patient has PHPT. A prospective trial is necessary to assess its usefulness in a larger population and in patients with elevated PTH concentration.

Rationale: The impact of chronic kidney disease (CKD) on vital impetus is poorly documented in patients not undergoing renal dialysis and discrepancies can be observed between patients and physicians in perception of QoL and impact of the disease., Methods: A self-questionnaire was sent to 1282 French nephrologists and a mirrored self-questionnaire was given to patients (CKD stage 3, 4 or 5) by their nephrologist. Data were collected prospectively and anonymously., Results: A total of 261 nephrologists and 172 patients participated in the survey. Sixty-six percent of patients reported a negative impact of the disease on their quality of life, which is also identified by nephrologists: important impact 22% vs 27%, mild or inconstant 44% vs 47%, mild or absent 34% vs 31% in patients and nephrologists, respectively. They had different perceptions about factors contributing to vital force; in particular, nephrologists underestimated their key role in psychological support. Indeed, the optimism and encouragements of nephrologists were considered to be a key factor of vital force for 60% of patients vs 20% of nephrologists (P<0,001). During consultations, nephrologists were primarily focused on biological abnormalities and adherence to treatment while mood or sexual disorders were rarely investigated. The main objective of treatment was to maintain a normal life for patients and to delay dialysis for nephrologists., Conclusion: Nephrologists have a relative knowledge of CKD impact on the vital impetus of patients, but there are differences of perception. It could be improved through specific trainings., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Acid-base regulation is essential to maintain homeostasis in humans. Carbonic acid/bicarbonate (H 2 CO 3 /HCO 3 - ) couple is the most predominant extracellular buffer to keep plasma pH within a physiological range. The ability to (re)generate such a buffer is a key milestone that necessitates to understand a precise physiology of both renal tubule and digestive tract. Here, we first reviewed renal and digestive cycles of bicarbonate in physiology. We also reviewed pathological findings where acid-base disequilibrium is involved and nutritional and/or alkali therapy could be necessary. Secondly, data from clinical trials were synthesized. Alkali therapy, oral and parenteral, from mineral-based water, masterful preparations or pharmaceutics drugs, is regularly used in a wide range of clinical findings, even if supporting data are (often) of a low level of evidence. Bicarbonate is primarily used during contrast-induced nephropathy, metabolic acidosis in chronic kidney disease or nephrolithiasis in which alkaline urine is necessary. Cast nephropathy, rhabdomyolysis and tumor lysis syndrome make usually physicians prescribe alkali therapy even if this prescription is only supported by physiopathological data without any proven clinical results. Finally, bicarbonate is essential in the composition of dialysate in both hemodialysis and peritoneal dialysis., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Two end-stage renal disease (ESRD) risk calculators were recently developed by Grams et al., and Ibrahim et al. to calculate ESRD risk before donation among living kidney donors. However, those calculators have never been studied among potential donors for whom donation was refused due to medical contraindications and compared to a group of donors. We compared 15-year and lifetime ESRD risk of donors and nondonors due to medical cause as estimated by those two calculators. Nondonors due to medical cause (n = 27) had a significantly higher 15-year ESRD risk compared to donors (n = 288) with both calculators (0.25 vs. 0.14, P < 0.001 for that developed by Grams et al. and 2.21 vs. 1.43, P = 0.002 for that developed by Ibrahim et al.). On the contrary, lifetime ESRD risk was not significantly different between the two groups. At both times (15 years and lifetime), we observed a significant overlap of ESRD risk between the two groups. ESRD risk calculators could be complementary to standard screening strategy but cannot be used alone to accept or decline donation., (© 2017 Steunstichting ESOT.)

Background and Objectives: Hypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia., Materials and Methods: This retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 μmol/min and defined idiopathic hypocitraturia., Results: Eleven patients (16.4%) had low HCO3- and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24-0.47] vs. 0.22 [0.08-0.37] mmol/mmol creatinine (P = 0.04)., Conclusions: Patients with hypocitraturia and normal plasma HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention.

Urolithiasis: assessment and metabolic management. Nephrolithiasis is a very common and recurrent disease. A minimal biological assessment is indicated in all patients. A more detailed biological investigation can be required according to the results of the first biological screening, or in case of recurrence, or in first intention depending on the medical history or on the consequences of renal calculi. Stone analysis (morphologic and using infra-red spectrophotometry) is the cornerstone for the understanding of the underlying pathophysiological processes. An appropriate imaging modality should be performed in order to detect urinary tract malformation in case of multiple or recurrent renal calculi. A medical treatment including at least dietary modifications must be prescribed to prevent stone recurrence and the potential risk of chronic kidney disease. Medical and dietary management should be individualized according to each type of stones., Competing Interests: C. Prot-Bertoye déclare des activités de conseil pour Biohealth. J.-P. Bertocchio déclare avoir des liens ponctuels avec Otsuka (formations) et Roche (conseil) et avoir été pris en charge lors de congrès par Fresenius Medical Care, Roche, Hemotech, Otsuka, Alexion et Roche. M. Daudon déclare avoir été pris en charge lors de congrès par Danone. M. Courbebaisse déclare des liens ponctuels (interventions et prise en charge lors de congrès) avec Biohealth.

Nephrolithiasis is a very common (prevalence around 10 to 12% in France) and recurrent disorder. Nephrolithiasis is associated to chronic kidney disease and is responsible for 2 to 3% of cases of end-stage renal disease, mainly if it is associated to nephrocalcinosis or to a monogenic disorder (1.6% of nephrolithiasis in adults, among them 1% of cystinuria). To understand the underlying pathophysiological processes, stone analysis (morphology and using infrared spectrophotometry) as well as minimal biological assessment including urine crystal research are required. The calcic nephrolithiasis is the more frequent subtype (>80%). Its medical treatment relies on simple dietary rules: non-alkaline hyperdiuresis>2 liters/day, calcium intake normalization (1 gram per day divided between the three principal meals), normalization of sodium (6 to 7 grams per day) and protein intake (1g/kg of theoretical body weight/day), and eviction of foods rich in oxalate. In case of persistent hypercalciuria (>0.1mmol/kg of theoretical body weight/day on free diet), a thiazide diuretic can be started while being aware to correct iatrogenic decrease in plasma potassium and urine citrate excretion. Measurement of bone mineral density must systematically be performed in patients with high 24 h-urinary calcium excretion. The medical treatment of uric acid nephrolithiasis relies on alkaline hyperdiuresis (goal of urine pH: 6.2 to 6.8). The use of allopurinol is justified only if urine uric acid is over 4mmol/day. Thanks to a well-managed preventive medical treatment, one can expect to stop the activity of nephrolithiasis in more than 80% of cases, making it one of the most accessible renal pathologies to preventive medical treatment., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m 2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m 2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m 2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m 2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m 2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m 2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction Hyperphosphatemia and cardiovascular mortality are associated particularly with end-stage renal disease. Available therapeutic strategies (i.e., diet restriction, calcium [or not]-based phosphate binders, calcimimetics) are associated with extrarenal blood purification. Compartmentalization of phosphate limits its depuration during hemodialysis. Several studies suggest that plasmatic pH is involved in the mobilization of phosphate from intracellular to extracellular compartments. Consequently, the efficiency of modified bicarbonate conductivity to purify blood phosphate was tested. Methods Ten hemodialysis patients with chronic hyperphosphatemia (>2.1 mmol/L) were included in the two three-sessions-per week periods. Bicarbonate concentration was fixed at 40 mmol/L and 30 mmol/L in the first and second periods, respectively. Phosphate depuration was evaluated by phosphate mobilization clearance (K M ). Findings Although bicarbonatemia was lower during the second period (21.0 ± 2.7 vs. 24.4 ± 3.1 mmol/L, P < 0.01), no difference was observed in phosphatemia (2.4 ± 0.5 vs. 2.3 ± 0.4 mmol/L, P = NS). The in-session variation of phosphate was lower (-1.45 ± 0.42 vs. -1.58 ± 0.44 mmol/L, P < 0.05) and K M was higher during the second period (82.94 ± 38.00 vs. 69.74 ± 24.48 mL/min, P < 0.05). Discussion The decrease of in-session phosphate and the increase in K M reflect phosphate refilling during hemodialysis. Thus, modulation of serum bicarbonate may play a role in controlling the phosphate pool. Even though correcting metabolic acidosis during hemodialysis remains important, alkaline excess can impair phosphate mobilization clearance. Clinical trials are needed to test the efficiency and relevance of a strategy where bicarbonatemia is corrected less at the beginning of sessions., (© 2016 International Society for Hemodialysis.)

Context: Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous condition resembling primary hyperparathyroidism (PHPT) but not curable by surgery; FHH types 1, 2, and 3 are due to loss-of-function mutations of the CASR, GNA11, or AP2S1 genes, respectively., Objective: This study aimed to compare the phenotypes of patients with genetically proven FHH types 1 or 3 or PHPT., Design, Setting, and Patients: This was a mutation analysis in a large cohort, a cross-sectional comparison of 52 patients with FHH type 1, 22 patients with FHH type 3, 60 with PHPT, and 24 normal adults., Intervention: There were no interventions., Main Outcome Measures: Abnormalities of the CASR, GNA11, and AP2S1 genes, blood calcium, phosphate, and PTH concentrations, urinary calcium excretion were measured., Results: In 133 families, we detected 101 mutations in the CASR gene, 68 of which were previously unknown, and in 19 families, the three recurrent AP2S1 mutations. No mutation was detected in the GNA11 gene. Patients with FHH type 3 had higher plasma calcium concentrations than patients with FHH type 1, despite having similar PTH concentrations and urinary calcium excretion. Renal tubular calcium reabsorption levels were higher in patients with FHH type 3 than in those with FHH type 1. Plasma calcium concentration was higher whereas PTH concentration and urinary calcium excretion were lower in FHH patients than in PHPT patients. In patients with FHH or PHPT, all data groups partially overlapped., Conclusion: In our population, AP2S1 mutations affect calcium homeostasis more severely than CASR mutations. Due to overlap, the risk of confusion between FHH and PHPT is high.

Background: Animal studies have highlighted the role of vascular mineralocorticoid receptor during Cyclosporine A-induced nephrotoxicity. Mineralocorticoid receptor antagonists could improve kidney survival but are not commonly used during renal impairment and in association with several immunosuppressive drugs due to a supposed higher risk of adverse events. We tested the tolerance of eplerenone according to its expected adverse events: hyperkalemia, metabolic acidosis, hypotension, acute kidney failure, or any other adverse event., Methods: We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73 m2) and receiving cyclosporine A. All patients received eplerenone 25 mg/d for 8 weeks. Serum potassium, renal function and expected adverse events were closely monitored., Results: Eight patients experienced mild hyperkalemia (>5 mmol/L), one moderate hyperkalemia (>5.5 mmol/L) and had to receive potassium-exchange resin. No severe hyperkalemia (>6 mmol/L) occurred. One acute kidney failure was observed, secondary to diarrhea. Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively). A cut-off value of 4.35 mmol/L for basal serum potassium was the best factor to predict the risk of developing mild hyperkalemia (>5 mmol/L)., Conclusions: Until eGFR falls to 30 mL/min/1.73 m2, eplerenone could be safely given to kidney-transplant recipients receiving cyclosporine A, if kalemia is closely monitored. When renal function is impaired and if basal kalemia is >4.35 mmol/L, then clinicians should properly balance risk and benefit of eplerenone use and offer dietary advice. An adequately powered prospective randomized study is now needed to test its efficiency (and safety) in this population., Trial Registration: ClinicalTrials.gov NCT01834768.

Alkali therapy is frequently used during chronic kidney disease and nephrolithiasis: nephrologists and urologists are the key operators. Very few is known about the underlying conditions of such a prescription: the aim of this study was to delineate those determinants. We conducted a prospective survey where French nephrologists and urologists were involved. Responders were without gender distinction and principally nephrologists. Prescription frequency was associated with gender (women), specialty (nephrologists), indications and perceived efficiency. Urologists prescribe more often during nephrolithiasis and nephrologists during chronic kidney disease. Urologists were more expert (by scoring on mineral-based alkaline waters compositions knowledge). By multivariate analysis, prescription frequency is associated with gender (women), indications and perceived efficiency by prescribers, which is itself influenced by feedback from patients. These results could have been influenced by a huge representation of nephrologists but foster physicians to go on listening to feedback from patients, due to a lack of clinical trials on the efficiency of mineral-based alkaline waters in such a field. Finally, physicians' education (especially young nephrologists) on mineral-based alkaline waters should be intensified., (Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Calcineurin inhibitors such as cyclosporine A (CsA) are still commonly used after renal transplantation, despite CsA--induced nephrotoxicity (CIN), which is partly related to vasoactive mechanisms. The mineralocorticoid receptor (MR) is now recognized as a key player in the control of vascular tone, and both endothelial cell- and vascular smooth muscle cell (SMC)-MR modulate the vasoactive responses to vasodilators and vasoconstrictors. Here we tested whether vascular MR is involved in renal hemodynamic changes induced by CsA. The relative contribution of vascular MR in acute CsA treatment was evaluated using mouse models with targeted deletion of MR in endothelial cell or SMC. Results indicate that MR expressed in SMC, but not in endothelium, contributes to the increase of plasma urea and creatinine, the appearance of isometric tubular vacuolization, and overexpression of a kidney injury biomarker (neutrophil gelatinase--associated lipocalin) after CsA treatment. Inactivation of MR in SMC blunted CsA--induced phosphorylation of contractile proteins. Finally, the in vivo increase of renal vascular resistance induced by CsA was blunted when MR was deleted from SMC cells, and this was associated with decreased L-type Ca2D channel activity. Thus, our study provides new insights into the role of vascular MR in renal hemodynamics during acute CIN, and provides rationale for clinical studies of MR antagonism to manage the side effects of calcineurin inhibitors., Competing Interests: All the authors declared no competing interests.

Hyponatremia could be defined as a public health topic: too many patients are concerned in both hospitalized and general populations; hyponatremia induces lots of clinical outcomes and a great economic burden. Its pathophysiology involves thirst regulation (hypotonic water intakes) and losses regulation (through the kidney under vasopressin control). Diagnostic approach should insure that hyponatremia reflects hypo-osmolality and hypotonicity: first, a false hyponatremia should be ruled out, then a non-hypotonic one. Next step is clinic: extracellular status should be evaluated. When increased, any edematous status should be evoked: heart failure, liver cirrhosis or nephrotic syndrome. When decreased, any cause of extracellular dehydration should be evoked: natriuresis could help distinguishing between renal (adrenal insufficiency, diuretics use or salt-losing nephropathy) or extrarenal (digestive mostly) etiologies. When clinically normal, a secretion of inappropriate antidiuretic hormone (SIADH) should be evoked, once hypothyroidism or hypoadrenocorticism have been ruled out. Therapy depends on the severity of the clinical impact. From extracellular rehydration, through fluid restriction, the paraneoplastic and heart failure-induced SIADH benefit from a new class of drug, available among the therapeutic strategies: aquaretics act through antidiuretic hormone receptor antagonism (vaptans). Their long-term benefits still have to be proven but it is a significant step forward in the treatment of hyponatremias., (Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Serum protein electrophoresis is commonly used in case of acute or chronic renal failure. It can lead to the etiologic diagnosis by detecting monoclonal gammopathies which are frequently complicated by renal failure, such as cast nephropathy, Randall's disease or amyloidosis, or to explore an associated inflammatory syndrome. We report the occurrence of two monoclonal components in a patient without any monoclonal component 10 days earlier. The sudden appearance of these two monoclonal components associated to the context of sepsis of urinary origin suggested the diagnosis of transient monoclonal gammopathy. This hypothesis was confirmed by monitoring serum protein electrophoresis that showed a gradual decrease of these two monoclonal components few weeks after the resolution of the infectious disease. The main etiological factors of transient monoclonal gammopathies are infectious or autoimmune diseases. In this context, it is important to delay the achievement of serum protein electrophoresis after the acute episode, in order to avoid to falsely conclude to hematologic malignancy diagnosis. This can prevent costly biological examinations of these transient monoclonal gammopathies and invasive procedures like bone marrow examination.

Slowing the progression of chronic kidney diseases needs new efficient treatments. Aldosterone classically acts on the distal nephron: it allows sodium reabsorption, potassium secretion and participates to blood volume control. Recently, new targets of aldosterone have been described including the heart and the vasculature but also non-epithelial kidney cells such as mesangial cells, podocytes and renal fibroblasts. The pathophysiological implication of aldosterone and its receptor, the mineralocorticoid receptor has been demonstrated ex vivo in cell culture and in vivo in experimental animal models with kidney damages such as diabetic and hypertensive kidney nephropathies, chronic kidney disease and glomerulopathies. The beneficial effects of the pharmacological antagonists of the mineralocorticoid receptor are independent of the hypertensive effect of aldosterone, indicating that blocking the activation of the mineralocorticoid receptor in these non-classical renal targets may be of clinical importance. Several clinical studies now report benefit and safety when using spironolactone or eplerenone, the currently available mineralocorticoid receptor antagonists, in patients with kidney diseases. In this review, we discuss the recent results reported in experimental and clinical research in this domain., (Copyright © 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)

Slowing the progression of chronic kidney diseases (CKDs) requires new and effective treatment approaches. Aldosterone classically acts on the distal nephron: it facilitates sodium reabsorption, potassium secretion, and participates in blood pressure control. Recently, new targets of aldosterone have been described including the heart and the vasculature, and other kidney cells such as mesangial cells, podocytes, and renal fibroblasts. The pathophysiological implications of increased mineralocorticoid receptor (MR) expression and activation (either dependent on aldosterone or direct ligand-independent activation) and its blockade have been illustrated with ex vivo in cell cultures and in vivo in experimental animal models of CKD, including diabetic and hypertensive nephropathies, and glomerulopathies. The beneficial effects of the MR antagonists are independent of the hypertensive effect of aldosterone, indicating that blocking the activation of the MR may have unique clinical importance. Several studies have reported efficacy and safety studies with spironolactone or eplerenone in patients with kidney diseases. In this review, we discuss the recent results reported in experimental and clinical research in this field, and emphasize the direct activation of the MR that can occur in pathological states associated with CKD, even in the absence of increased circulating levels of aldosterone.

Several alternative anticoagulation drugs are now available for patients with heparin induced thrombocytopenia type II (HIT II). However, their indication is not yet reaching a consensus. Moreover, some of them have not yet their marketing approval. The importantly use in hemodialyzed patients should be taken with caution since most of them are excreted by the kidneys. The use of fondaparinux, which exerts high anti-Xa activity, is not well documented. We report here our experience on the use of fondaparinux in an hemodialyzed patient with HIT II, not only as anticoagulation during hemodialysis sessions but also as interdialytic anticoagulation locking solution of her central venous catheter. The use of fondaparinux seems to us simple enough (even if its ready-for-use syringe requires adjustments to deliver the required doses) and its efficacy, safety and economic cost lead us to think that it is an indication of choice for an alternative anticoagulation in hemodialyzed patients with HIT II. Control prospective trials should be performed in order to confirm the preliminary favourable data and to support the proposal of marketing approval in this indication., (Copyright © 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.)