Jean Kaufman

Preservation of volumetric bone density and geometry in trans women during cross-sex hormonal therapy: a prospective observational study

SummaryAlthough trans women before the start of hormonal therapy have a less bone and muscle mass compared with control men, their bone mass and geometry are preserved during the first 2xa0years of hormonal therapy, despite of substantial muscle loss, illustrating the major role of estrogen in the male skeleton.PurposeThe aim of this study is to examine the evolution of areal and volumetric bone density, geometry, and turnover in trans women undergoing sex steroid changes, during the first 2xa0years of hormonal therapy.MethodsIn a prospective observational study, we examined 49 trans women (male-to-female) before and after 1 and 2xa0years of cross-sex hormonal therapy (CSH) in comparison with 49 age-matched control men measuring grip strength (hand dynamometer), areal bone mineral density (aBMD), and total body fat and lean mass using dual X-ray absorptiometry (DXA), bone geometry and volumetric bone mineral density, regional fat, and muscle area at the forearm and calf using peripheral quantitative computed tomography. Standardized treatment regimens were used with oral estradiol valerate, 4xa0mg daily (or transdermal 17-β estradiol 100xa0μg/24xa0h for patients >45xa0years old), both combined with oral cyproterone acetate 50xa0mg daily.ResultsPrior to CSH, trans women had lower aBMD at all measured sites (all pu2009<u20090.001), smaller cortical bone size (all pu2009<u20090.05), and lower muscle mass and strength and lean body mass (all pu2009<u20090.05) compared with control men. During CSH, muscle mass and strength decreased and all measures of fat mass increased (all pu2009<u20090.001). The aBMD increased at the femoral neck, radius, lumbar spine, and total body; cortical and trabecular bone remained stable and bone turnover markers decreased (all pu2009<u20090.05).ConclusionsAlthough trans women, before CSH, have a lower aBMD and cortical bone size compared with control men, their skeletal status is well preserved during CSH treatment, despite of substantial muscle loss.

Taxonomy of rare genetic metabolic bone disorders

SummaryThis article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes.IntroductionRare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients.MethodsIOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis.ResultsThis taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity.ConclusionsThis article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

Association of spontaneous 3-year changes in physical function with subsequent 15-year mortality in community-dwelling older men

Chronic pain is defined as pain lasting longer than six weeks and is one of the main complaints in elderly subjects. Frailty is a pathological condition that increases an individuals vulnerability by diminishing their homeostatic reserve, and it is considered a mortality risk factor. We examined the association between chronic pain and frailty in subjects who were recruited from a check-up clinic in Mexico City. Chronic pain and frailty were evaluated in 131 subjects through validated questionnaires. Descriptive and analytical statistics were performed. Of the participants, 41.9% presented with chronic pain, and 12.2% were frail. The unadjusted OR for the presence of frailty in subjects with chronic pain was 14.3 (95%CI 3.0-67.8), and the phi coefficient showed a weak positive correlation between the variables (Φ=0.352, p<0.001). In conclusion, chronic pain is associated with a higher risk of frailty. Well-timed diagnosis and treatment of chronic pain can help prevent dependency in these individuals.

Factors regulating 1,25-dihydroxyvitamin D3 concentrations in liver transplant recipients

Abstracts 48th ESPN Meeting, Brussels, September 2015s 48th ESPN Meeting, Brussels, September 2015 O 01 CAN EARLY RECOGNITION OFAKI IN CHILDREN BE ACHIEVED BY USING AN ALGORITHM (PRELIMINARY RESULTS): ON BEHALF OF BRITISH ASSOCIATION FOR PAEDIATRIC NEPHROLOGY Jelena Stojanovic, Nabil Melhem, Sheetal Bhojani, Manish D Sinha, David Milford Evelina London Childrens Hospital, London, UK; Royal Hospital for Sick Children, Glasgow, Scotland; Birmingham Childrens Hospital, Birmingham, UK Introduction: The aim of the study was to validate recently proposed algorithm ‘Standardising early identification of Acute Kidney Injury’ introduced byNHSEngland in a paediatric setting and to investigate recognition and management of AKI. This multi-centre national project was supported by UK Renal Registry and British Association for Paediatric Nephrology. Material and methods: In part one of the audit, all creatinine measurements performed at each of six centres over a six month period were evaluated electronically using the algorithm. In part two, 180 children from six centres were randomly selected and their case notes reviewed. Here, we report preliminary results on data analysed from two tertiary children’s and one district general hospital in the UK. Information was obtained from paper and electronic patient’s notes. AKI stage 1 is a rise of >1.5x baseline creatinine level; AKI stage 2 is a rise of>2x baseline and AKI stage 3 is a rise of>3x baseline. Results: 33,663 creatinine measurements were analysed during the study period using the AKI algorithm.We identified 1,940 AKI 1 episodes (604 children), 479 AKI 2 (158 children) and 756 AKI 3 (112 children). Overall 666 unique children had one or more AKI episodes.We reviewed case notes of 66 children (39 boys) age range 28 days to 17 years. On clinical review of case notes, AKI was recognised in 18 patients (27.3%) only. Of all patients, 17% had prexisting renal condition. 94% children had a follow up arranged with creatinine normalising in 75% of those tested. A third of patients had urine tested and two thirds had medication dosage adjusted to estimated GFR. Conclusions: The proposed algorithm provides an electronic means of identifying children with AKI and highlighting its severity. Our preliminary data suggest that AKI remains clinically under recognised in clinical settings. Timely recognition and optimal management of AKI is important to improve longer term renal outcomes. O 02 EPIGENETIC REGULATION BY HDAC PROTEINS PLAYSACRITICALROLE INTHEPROGRESSIONOFRENAL FIBROSIS Scott Manson, Qiusha Guo, Katelynn Moore, Paul Austin Washington University, Washington, The United States of America Introduction: Chronic kidney disease is associated with changes in the expression of approximately 10% of the genome. The histone deacetylases (HDACs) are a family of 10 related proteins which are among the most widely expressed and crucial regulators of gene transcription. In this study, we examine the biologic and therapeutic importance of HDAC proteins during disease progression. Material and methods: Chronic renal injury was modeled in vivo in mice by unilateral ureteral obstruction (UUO). The role of HDAC proteins was assessed by using a variety of molecular techniques and treatment with the broad spectrumHDAC inhibitor Trichostatin A (TSA). Results:UUO leads to a dramatic increase in the protein levels of 9 of the 10 HDAC isoforms. Notably, there is a 6.1-fold increase in HDAC8 expression that localizes specifically to pericyte-derived myofibroblasts, the cell population which accounts for the majority of matrix production during renal fibrosis. To better understand the importance of these findings, we treated mice with the HDAC inhibitor TSA. This resulted in a 3.4-fold increase in the anti-fibrotic gene BMP7, a 41.6% decrease in the matrix protein COLIA1, and a 61.6% decrease in the myofibroblast differentiation marker α-SMA following UUO. These changes in gene expression culminate in a 77.9% decrease in the interstitial proliferative response, a 43.0% decrease in myofibroblast number, 31.1% decrease in renal fibrosis, 42.8% decrease in apoptosis, and a 43.4% decrease in the loss of renal architecture. [All results are p<0.05] Conclusions: Chronic renal injury is associated with a dramatic increase in HDAC protein levels that stimulates pro-fibrotic gene expression and suppresses anti-fibrotic gene expression. Importantly, treatment with HDAC inhibitors reverses these changes in gene expression and inhibits the development of renal fibrosis. This suggests that HDAC inhibitors may serve as effective therapies to inhibit disease progression. O 03 ECULIZUMAB TREATMENT IN SEVERE PEDIATRIC STEC-HUS, A MULTICENTRIC RETROSPECTIVE STUDY Percheron Lucas, Gramada Raluca, Decramer Stephane, Harambat Jerome, Eckart Philippe, Bourdat-michel Guylhene, Leroy Valerie, Sellier-leclerc Anne-laure, Adra Anne-laure, Allain-launay Emma, Berard Etienne, Bouchireb Karim, Fila Marc, Pietrement Christine, Merieau Elodie, Lapeyraque Anne-laure, Chehade Hassid, Fremeaux-bacchi Veronique, Dimeglio Chloe, Garnier Arnaud Service De Nephrologie Medecine Interne, Hopital Des Enfants, Chu Purpan, Toulouse, France; Service De Neuroradiologie Diagnostique Et Thérapeutique, Chu Purpan, Toulouse, France; Service De Nephrologie Pediatrique, Hopital Pellegrin-enfants, Chu Bordeaux, Bordeaux, France; Service De Pediatrie Medicale, Hopital Cote De Nacre, Chu Caen, Caen, France; Service De Pediatrie, Hopital Couple-enfants, Chu Grenoble, Grenoble, France; Service De Nephrologie Pediatrique, Hopital Jeanne De Flandre, Chu Lille, Lille, France; Service De Nephrologie Pediatrique, Hopital Femme Mere Enfant, Hospices Civils De Lyon, Lyon, France; Service De Nephrologie Pediatrique, Hopital Arnaud De Villeneuve, Chu Montpellier, Montpellier, France; Service De Nephrologie Pediatrique, Hopital Mere-enfants, Chu Nantes, Nantes, France; Service De Nephrologie Pediatrique, Hopital Archet 2, Chu Nice, Nice, France; Service De Nephrologie Pediatrique, Hopital Necker Enfants Malades, Assistance Publique-hopitaux De Paris, Paris, France; Service De Nephrologie Pediatrique, Hopital Robert Debre-paris, Assistance Publique-hopitaux De Paris, Paris, France; Service De Pediatrie, Hopital Americain, Chu Reims, Reims, France; Service De Nephrologie, Hopital Clocheville, Chu Tours, Tours, France; Service De Nephrologie Pediatrique, Chu De Sainte-justine, Montreal, Canada; Service De Nephrologie Pediatrique, Chu De Lausanne, Lausanne, Switzerland; Laboratoire D’immunologie, Hopital Europeen Georges Pompidou, Assistance Publique-hopitaux De Paris, DOI 10.1007/s00467-015-3158-7 Pediatr Nephrol (2015) 30:1543–1730• OnabotulinumtoxinA is a safe and effective treatment for therapy resistant OAB in non-neuropathic children. • It can be a useful treatment option for therapy resistant incontinence and/or enuresis. • With one single treatment, over 50% cure rate may be achieved in a therapy resistant patient population. • The aim of this study is to analyze results and side effects after OnabotulinumtoxinA detrusor injection treatment in children in order to define its place in the treatment of non-neuropathic OAB • Effect on both incontinence and enuresis is reported. • Therapy resistant enuresis is to our knowledge not previously reported as indication for the use of OnabotulinumtoxinA RESULTS OF ONABOTULINUMTOXIN-A IN CHILDREN WITH THERAPY RESISTANT OVERACTIVE BLADDER: 10-YEAR EXPERIENCE