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2. Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

Author

Phan, V, Blydt-Hansen, T, Feber, J, Alos, N, Arora, S, Atkinson, S, Bell, L, Clarson, C, Couch, R, Cummings, EA, Filler, G, Grant, RM, Grimmer, J, Hebert, D, Lentle, B, Ma, J, Matzinger, M, Midgley, J, Pinsk, M, Rodd, C, Shenouda, N, Stein, R, Stephure, D, Taback, S, Williams, K, Rauch, F, Siminoski, K, Ward, LM, and the Canadian STOPP Consortium

Subjects
Allied Health and Rehabilitation Science, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Clinical Research, Osteoporosis, Pediatric, Musculoskeletal, Adolescent, Anthropometry, Bone Density, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Glucocorticoids, Humans, Infant, Lumbar Vertebrae, Male, Nephrotic Syndrome, Osteoporotic Fractures, Spinal Fractures, Canadian STOPP Consortium, Biomedical Engineering, Public Health and Health Services, Endocrinology & Metabolism, Clinical sciences, Epidemiology
Abstract

UnlabelledIncident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.IntroductionVertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.MethodsVF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.ResultsSixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017).ConclusionsThe incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

Published
2014

3. Effects of pediatric chronic kidney disease and its etiology on tissue sodium concentration: a pilot study

Author

Salerno, F. R., Akbari, A., Lemoine, S., Scholl, T. J., Mcintyre, C. W., Filler, G., CarMeN, laboratoire, London Health Sciences Center (LHSC), Western University [London, ON, Canada], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ontario Institute for Cancer Research [Canada] (OICR), and Ontario Institute for Cancer Research

Subjects
[SDV] Life Sciences [q-bio], Etiology, Nephrology, [SDV]Life Sciences [q-bio], Pediatrics, Perinatology and Child Health, Ckd, Tissue sodium concentration
Abstract

International audience; BACKGROUND: Sodium-23 magnetic resonance imaging ((23)Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na(+)]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na(+)] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na(+)] compared to healthy controls. METHODS: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg (23)Na MRI for tissue [Na(+)] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na(+)] was compared against healthy controls by computing individual Z-scores. An absolute Z-score \textgreater 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na(+)] and kidney function. RESULTS: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na(+)] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na(+)] Z-scores. Reduced whole-leg [Na(+)] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na(+)] measures were significantly associated with proteinuria and hypoalbuminemia. CONCLUSIONS: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na(+)] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information.

Published
2022
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33. ERTRAGS- UND PREISINSTABILITÄT AUF AGRARMÄRKTEN IN DEUTSCHLAND UND DER EU

Author

Artavia, M., Deppermann, A., Filler, G., Grethe, H., Häger, A., Kirschke, D., and Odening, M.

Subjects
Preisvolatilität, Agricultural and Food Policy, International Relations/Trade, Risk and Uncertainty, Unsichereit, Demand and Price Analysis, Agrarpolitik, Gemeinsame Agrarpolitik, Ertragsschwankungen
Abstract

Die Preisvolatilität hat in Deutschland im Zeitraum 1993-2008 für wichtige Agrarprodukte (Weizen, Gerste und Milch) vor allem aufgrund der Deregulierung der EU-Märkte zugenommen. Für andere Produkte hat sich die Preisvolatilität in diesem Zeitraum wenig geändert, was vor allem daran liegt, dass das Ausmaß der Marktregulierung über diesen Zeitraum stabil war. Im Rahmen von Simulationen mit dem Agrarsektormodell ESIM wurde gezeigt, dass es aufgrund der starken Weltmarktintegration bei Weizen, Gerste und Raps keinen erlösstabilisierenden Zusammenhang zwischen den Ertrags- und den Preisschwankungen in Deutschland gibt, da das auch in Deutschland maßgebliche Weltmarktpreisniveau nicht wesentlich durch das Ertragsniveau in Deutschland determiniert wird. Ein potenzieller Anstieg der globalen Ertragsvariabilität, der sich langfristig in Folge des globalen Klimawandels einstellen könnte, würde zu einem Anstieg der Preisvolatilität führen. Forderungen nach einer staatlichen Subventionierung von Ernteversicherungen aufgrund des hohen systemischen Risikos und daraus resultierenden Marktversagens haben in den letzten Jahren zugenommen. Bisher fehlt allerdings der empirische Nachweis dafür, dass das systemische Risiko in seiner Höhe nicht durch marktwirtschaftliche Instrumente und ohne Subventionierung beherrschbar ist., C2_2

Published
2010
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34. Rituximab in fefractory nephrotic syndrome

Author

Prytula, Agnieszka, Iijima, K, Kamei, K, Geary, D, Gottlich, E, Majeed, A, Taylor, M, Marks, S, Tuchman, SA, Camilla, R, Ognjanovic, M, Filler, G, Smith, G, Tullus, K, and Pediatrics

Published
2010

40. Eculizumab Dosing in Infants.

Author

Kobrzynski, M., Wile, B., Huang, S. S., and Filler, G.

Subjects
THERAPEUTIC use of monoclonal antibodies, TRIMETHYLAMINURIA, BLOOD transfusion, HEMOLYTIC-uremic syndrome, MONOCLONAL antibodies, WEIGHT loss, TREATMENT effectiveness, CHILDREN, DIAGNOSIS
Abstract

Eculizumab is the therapy of choice for patients with atypical hemolytic uremic syndrome (aHUS). Dosing recommendations stem from two trials: one retrospective trial (19 children and 5 infants) and one prospective trial (22 patients and 5 infants). This case report highlights the need for more precise dosing recommendations in children, particularly in infants, and for smaller vials of the medication to facilitate more precise dosing. Such changes would ensure that adverse events are minimized and that the children with aHUS who are treated with eculizumab experience an optimal clinical response. [ABSTRACT FROM AUTHOR]

Published
2018
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41. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome

Author

UCL - Cliniques universitaires Saint-Luc, UCL, Richards, A, Pirson, Yves, Kemp, EJ, Liszewski, MK, Goodship, JA, Lampe, AK, Decorte, R, Muslumanoglu, MH, Kavukcu, S, Filler, G, Wen, LS, Atkinson, JP, Goodship, THJ, UCL - Cliniques universitaires Saint-Luc, UCL, Richards, A, Pirson, Yves, Kemp, EJ, Liszewski, MK, Goodship, JA, Lampe, AK, Decorte, R, Muslumanoglu, MH, Kavukcu, S, Filler, G, Wen, LS, Atkinson, JP, and Goodship, THJ

Abstract

Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits complement activation by regulating Ob deposition on targets. Factor H mutations occur in 10-20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP mutations could predispose to HUS, and we sequenced MCP coding exons in affected individuals from 30 families. MCP mutations were detected in affected individuals of three families: a deletion of two amino acids (D237/S238) in family 1 (heterozygous) and a substitution, S206P, in families 2 (heterozygous) and 3 (homozygous). We evaluated protein expression and function in peripheral blood mononuclear cells from these individuals. An individual with the D237/S238 deletion had reduced MCP levels and approximate to50% C3b binding compared with normal controls. Individuals with the S206P change expressed normal quantities of protein, but demonstrated approximate to50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. MCP expression and function was evaluated in transfectants reproducing these mutations. The deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies.

Published
2003

42. Familial hemolytic uremic syndrome and mutations in membrane cofactor protein (MCP; CD46) of the complement system.

Author

UCL - Cliniques universitaires Saint-Luc, UCL, Richards, A, Pirson, Yves, Kemp, EJ, Liszewski, K, Goodship, JA, Lampe, AK, Decorte, R, Muslumanoglu, H, Kavukcu, S, Filler, G, Wen, LS, Atkinson, JP, Goodship, THJ, 36th Annual Meeting of the American-Society-of-Nephrology, UCL - Cliniques universitaires Saint-Luc, UCL, Richards, A, Pirson, Yves, Kemp, EJ, Liszewski, K, Goodship, JA, Lampe, AK, Decorte, R, Muslumanoglu, H, Kavukcu, S, Filler, G, Wen, LS, Atkinson, JP, Goodship, THJ, and 36th Annual Meeting of the American-Society-of-Nephrology

Published
2003

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