TmP/GFR reference values from childhood to adulthood in the era of IDMS-standardized creatinine values

International audienceBACKGROUND: The assessment of phosphate homeostasis in clinical practice relies on circulating phosphate levels but also on phosphate tubular reabsorption, ideally assessed using the Tubular maximum Phosphate Reabsorption per Glomerular Filtration Rate (TmP/GFR). TmP/GFR reference values were established before the onset of IDMS-standardized creatinine assays, and thus need to be updated. Our objective is to provide reference values for TmP/GFR from childhood to adulthood, using the gold-standard of GFR assessment and IDMS-standardized creatinine values. METHODS: We retrospectively analyzed all the inulin and iohexol clearances (mGFR) performed in children and in adults screened for a living-donation in our unit since the beginning of IDMS-creatinine assays. TmP/GFR was calculated on a fasting sample, using the conventional formula without correction for TRP in subjects below 19 years of age. RESULTS: A total of 2051 subjects (1711 children, 340 adults), aged from 1.9 to 73.4 years with normal GFR, normal phosphate and normal calcium levels, was included for TmP/GFR analysis. As expected, there was a progressive decrease along puberty in both genders of plasma phosphate and TmP/GFR, the decrease occurring earlier in girls. After the age of 19, there was a stabilization of plasma phosphate and TmP/GFR levels until the age of 55, phosphate levels and TmP/GFR being slightly lower in men than in women. CONCLUSION: We present the largest cohort describing TmP/GFR reference values in the era of IDMS-standardized creatinine assays. We believe that these data will help physicians to better diagnose and manage patients with abnormal phosphate metabolism in daily clinical routine

Development of a TPC detector for the ALICE experiment

A proportional chamber with ring cathode readout is foreseen for the ALICE Time Projection Chamber. It offers low gas gainoperation, light-weight construction and good pulse shape. The Tape Automatic Bonding (TAB) process makes it possible tomount the VLSI analog front end electronics directly on the back face of the multilayer board carrying the ring cathodeelements, yielding high channel density. At the same time, simulation work is done. Constructionand first results will bepresented

Progress in high density projection chambers

The high density projection chamber (HPC) is a sampling calorimeter where shower conversion and detection is separated. It offers a simple and homogeneous large volume detector with an energy resolution of (10-11)%/ square root E, an inherent resolution transverse to the shower axis of 100 mu m and an exceptionally fine granularity along the shower. The user of this detector in a colliding beam experiment will be discussed

Fluconazole in hypercalciuric patients with increased 1,25(OH)(2)D levels: the prospective, randomized, placebo-controlled, double-blind FLUCOLITH trial

International audienceBACKGROUND: Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)(2)D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)(2)D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)(2)D levels. METHODS: The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10-60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (\textgreater 0.1 mmol/kg/day), increased 1,25(OH)(2)D levels (\textgreater 150 pmol/L), and 25-OH-D levels \textgreater20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria. DISCUSSION: The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)(2)D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the "off-label" use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)(2)D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04495608 . Registered on July 23, 2020

Development of a time projection chamber with high two track resolution capability for experiments at heavy ion colliders

Experiments at future Heavy-Ion Colliders have to deal with unprecedented high particle fluxes. In the dedicated Heavy-Ion detector at LHC pattern recognition and particle identification are performed by a Time Projection Chamber that operates in a field free region or in a weak magnetic field (0.2T). A double track resolution of considerably < 10 mm, i.e. a factor of 2-4 better than in existing TPC's, is needed to cope with the high track density. Improvements in the readout modules, analog electronics and longitudinal and transversal single electron diffusion are proposed. The problem of data-acquisiton and -reduction is briefly addressed