Aurélia Bertholet-Thomas

CHU de Lyon - Hôpital Femme-Mère-Enfant, Lyons, Rhône-Alpes, France

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Publications (16)65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The management of tubulopathies after renal transplantation (RTx) may require high doses of sodium and bicarbonate, reducing the quality of life and therapeutic compliance of the patient. Some studies on adult patients have highlighted the benefits of fludrocortisone (fludro) in the treatment of severe tubulopathies.
    Pediatric nephrology (Berlin, Germany). 06/2014;
  • Aurelia Bertholet-Thomas, Justine Bacchetta, Velibor Tasic, Pierre Cochat
    New England Journal of Medicine 04/2014; 370(14):1366-7. · 51.66 Impact Factor
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    ABSTRACT: Due to technical requirements and cost, hemodiafiltration (HDF) is not widely used in pediatrics. We have been using online HDF (oHDF) since 2009 and we observed low parathyroid hormone (PTH) levels despite the accurate management of CKD-MBD. We reviewed the medical charts and parameters of mineral metabolism assessed on a before/after session basis in the 6 children undergoing chronic oHDF in our centre. We observed low (<80pg/mL) PTH levels in all 6 patients and very low (<45pg/mL) PTH levels in 5, two of them presenting with pathological fractures. These low PTH levels were reversed after decreasing calcium concentration to 1.25 mmol/L in the dialysate, suggesting that high-efficiency oHDF may expose children to calcium during sessions in a too important amount when using 1.5 mmol/L dialysates. Last, C-terminal FGF23 levels before sessions were relatively low (<1600RU/mL), with a 32% clearance by oHDF. PTH levels should be closely monitored in pediatric oHDF and solutions with a calcium concentration of 1.25 mmol/L should be used as first line in these patients.
    Néphrologie & Thérapeutique 12/2013; · 0.50 Impact Factor
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    ABSTRACT: BACKGROUND: Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS). METHODS: This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19 >1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %). RESULTS: Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred. CONCLUSION: The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.
    Pediatric Nephrology 01/2013; · 2.94 Impact Factor
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    ABSTRACT: Background Due to technical requirements and cost, hemodiafiltration (HDF) is not widely used in pediatrics. We have been using online HDF (oHDF) since 2009 and we observed low parathyroid hormone (PTH) levels despite the accurate management of CKD-MBD. Methods We reviewed the medical charts and parameters of mineral metabolism assessed on a before/after session basis in the 6 children undergoing chronic oHDF in our centre. Results We observed low (<80 pg/mL) PTH levels in all 6 patients and very low (<45 pg/mL) PTH levels in 5, two of them presenting with pathological fractures. These low PTH levels were reversed after decreasing calcium concentration to 1.25 mmol/L in the dialysate, suggesting that high-efficiency oHDF may expose children to calcium during sessions in a too important amount when using 1.5 mmol/L dialysates. Last, C-terminal FGF23 levels before sessions were relatively low (<1600 RU/mL), with a 32% clearance by oHDF. Conclusion PTH levels should be closely monitored in pediatric oHDF and solutions with a calcium concentration of 1.25 mmol/L should be used as first line in these patients.
    Néphrologie & Thérapeutique. 01/2013;
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    ABSTRACT: Data on long-term outcomes after pediatric renal transplantation (Tx) are still limited. We report on a 20-year single-center experience. Medical charts of all consecutive pediatric Tx performed between 1987 and 2007 were reviewed. Data of patients who had been transferred to adult units were extracted from the French databases of renal replacement therapies. Outcomes were assessed using Kaplan-Meier and Cox models. Two hundred forty Tx were performed in 219 children (24.1% pre-emptive and 17.5% living related donor Tx). Median age at Tx was 11.1 years and median follow-up was 10.4 years. Patient survival was 94%, 92%, and 91% at 5, 10, and 15 years post-Tx, respectively. Overall, transplant survival was 92%, 82%, 72%, and 59% at 1, 5, 10, and 15 years post-Tx, respectively. The expected death-censored graft half-life was 20 years. Sixteen patients developed malignancies during follow-up. Median height at 18 years of age was 166 cm in boys and 152 cm in girls with 68% of patients being in the normal range. The proportion of socially disadvantaged young people was higher than in general population. Excellent long-term outcomes can be achieved in pediatric renal Tx, but specific problems such as malignancies, growth, and social outcome remain challenging.
    Transplant International 12/2012; · 3.16 Impact Factor
  • P. Cochat, J. Bacchetta, J.-F. Sabot, A. Bertholet-Thomas, D. Demède
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    ABSTRACT: La lithiase urinaire est plus rare chez l’enfant que chez l’adulte, mais son éventualité doit être évoquée devant des tableaux cliniques variés, associant généralement douleur et hématurie. Cependant, il peut aussi s’agir d’une découverte fortuite. La prise en charge initiale repose avant tout sur le traitement de la colique néphrétique lorsqu’elle existe, voire sur un geste endoscopique. La nature de la lithiase est reconnue à partir de l’analyse du calcul par spectrophotométrie infrarouge, par l’étude de la cristallurie et parfois par un bilan biochimique orienté. La responsabilité des tubulopathies et des maladies héréditaires métaboliques est prédominante chez l’enfant, mais il peut aussi s’agir de lithiases infectieuses, de lithiases associées à des anomalies de l’écoulement des urines, ou de lithiases d’origine médicamenteuse. Le traitement chirurgical a cédé le pas aux méthodes endoscopiques et à la lithotritie extracorporelle et chaque étiologie guidera un traitement médical spécifique. Toutefois, la prévention de la récidive repose toujours sur la dilution des urines par l’hydratation abondante. Le pronostic dépend de l’affection causale, et notamment de l’existence ou non d’une néphrocalcinose et des éventuelles atteintes extrarénales, mais aussi de l’adéquation du traitement et de l’observance qui lui est associée.
    Journal de Pédiatrie et de Puériculture 10/2012; 25(5):255–268.
  • Archives de Pédiatrie. 06/2012; 19(6):653.
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    ABSTRACT: Graft survival is worse in recipient aged less than 5 years due to the greater risk of vascular thrombosis. Thrombosis may be prevented by the choice of the donor, method of surgery, perioperative hemodynamic optimisation and preventive anti-coagulation. Normal growth is a major objective of the management of transplanted children. The mean final height increased during the 20 last years to be between -1.63 and -0.92 SDS depending on age and period of the transplantation.
    Néphrologie & Thérapeutique 12/2011; 7(7):604-7. · 0.50 Impact Factor
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    ABSTRACT: Infectious risk is more important in the transplanted child than in adult because children are less often immunised against pathogens ant more exposed than adults to numerous infectious agents (virus but also bacteria including pneumococcus). The application of the standard immunisation schedule must be a permanent concern of transplantation (Tx) teams. Some vaccines that are not planned in the standard immunization schedule are particularly advised for the child and his family circle, as well as for caregivers. Immunisation response must be evaluated by a serological follow-up before Tx, in particular during the pre-Tx diagnostic work-up, then regularly after Tx. The more frequent absence of immunisation against Epstein Barr Virus (EBV) in children explains the increased frequency of post-transplant lymphoproliferative disorder at the pediatric age.
    Néphrologie & Thérapeutique 12/2011; 7(7):608-10. · 0.50 Impact Factor
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    ABSTRACT: Haemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy with acute renal failure, haemolytic anaemia with schizocytes and thrombocytopenia. Typical forms (D(+) HUS) are caused by gastrointestinal infection with Escherichia coli species producing verotoxines (or Shiga toxins, STEC). It is estimated that 5-8 % of infected individuals will develop HUS following STEC infection. E. coli O157:H7 is the most commonly involved serotype and can lead to D(+) HUS in 15 % of young infected children. Vehicles of STEC transmission are contaminated food (ground beef, unpasteurised dairy products, unwashed and uncooked fruit and vegetables), person-to-person transmission and contact with farm animals with STEC. After an average incubation period of 3 to 8 days, patients develop painful bloody diarrhoea followed by systemic toxinemia. This may lead to thrombotic microangiopathy with endothelial damage and activation of local thrombosis. Since 1996, the Institut de Veille Sanitaire (InVS) centralises all notified French cases of D(+) HUS in children less than 15 years of age and investigates cases regrouped by time and place for the presence of STEC risk factors. The average annual incidence ranges between 0.6 and one for 100 000 children younger than 15 years and with a peak at 1 year of age. Fifty-one percent of HUS occur between June and September. Patients with a suspicion of STEC infection or bloody diarrhoea should not receive antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs. Maintenance optimal hydration provides nephroprotection. The management of HUS remains supportive. Dialysis was required for 46 % of HUS cases in 2009. For similar indication, peritoneal dialysis has to be a first choice treatment. Neurological injury is the most frequent non-renal complication and the first cause of death. Early initiation of plasmapheresis might improve the prognosis. Overall mortality rate ranges between 1 and 5 %. One third of patients suffer from long-term renal morbidity such as proteinuria, arterial hypertension and decrease of glomerular filtration rate. The longer the duration of anuria, the greater the risk of sequellae. Any patient with a history of HUS needs a long-term renal follow-up.
    Archives de Pédiatrie 07/2011; 18(7):823-30. · 0.36 Impact Factor
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    ABSTRACT: Primary hyperoxalurias are rare recessive inherited inborn errors of glyoxylate metabolism. They are responsible for progressive renal involvement, which further lead to systemic oxalate deposition, which can even occur in infants. Primary hyperoxaluria type 1 is the most common form in Europe and is due to alanine-glyoxylate aminostransferase deficiency, a hepatic peroxisomal pyridoxin-dependent enzyme. Therefore primary hyperoxaluria type 1 is responsible for hyperoxaluria leading to aggressive stone formation and nephrocalcinosis. As glomerular filtration rate decreases, systemic oxalate storage occurs throughout all the body, and mainly in the skeleton. The diagnosis is first based on urine oxalate measurement, then on genotyping, which may also allow prenatal diagnosis to be proposed. Conservative measures - including hydration, crystallization inhibitors and pyridoxine - are safe and may allow long lasting renal survival, provided it is given as soon as the diagnosis has been even suspected. No dialysis procedure can remove enough oxalate to compensate oxalate overproduction from the sick liver, therefore a combined liver and kidney transplantation should be planned before advanced renal disease has occurred, in order to limit/avoid systemic oxalate deposition. In the future, primary hyperoxaluria type 1 may benefit from hepatocyte transplantation, chaperone molecules, etc.
    Néphrologie & Thérapeutique 05/2011; 7(4):249-59. · 0.50 Impact Factor
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    ABSTRACT: FS is an inherited disease characterized by male pseudohermaphroditism and glomerular involvement leading to end-stage renal disease during adolescence or early adulthood (J Pediatr 1964:64:740). The FS phenotype in 46,XY patients consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma, and development of renal failure in the second decade of life. FS is caused by heterozygous mutation in intron 9 of the WT1 leading to a change in splicing that results in loss of three amino acids (+KTS isoform), thus disrupting the normal ratio of the +KTS/-KTS isoforms that is critical for proper gonadal and renal development (Nat Genet 1997:17:467; Hum Mol Genet 1998:7:709). We report on a patient followed for FS revealed by acute peritoneal syndrome because of ovarian dysgerminoma. Therapeutic options had led to an unusual course with recurrent neoplastic disease after renal transplantation.
    Pediatric Transplantation 05/2011; 15(3):e53-5. · 1.50 Impact Factor
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    ABSTRACT: It has been demonstrated that alkylating agents such as cyclophosphamide (CYP) are effective in reducing the risk of relapse in frequently relapsing (FRNS) and steroid-dependent nephrotic syndrome (SDNS). Little is known about prognostic factors in SDNS and FRNS treated by CYP. The objectives of this study are to determine long-term outcomes and factors associated with sustained remission in these patients. We retrospectively studied the data from 143 children (104 boys) with SDNS and FRNS treated with CYP in six centres over 15 years. Relapse-free survival was estimated by Kaplan-Meier method. The determinants of long-term remission were assessed by univariate and multivariate analyses using Cox proportional hazard models. Median age at diagnosis was 3.7 years (interquartile range: IQR 2.3-5.9), and median follow-up was 7.8 years (IQR 4.0-11.8). CYP treatment was introduced after a median time of 1.7 years (IQR 0.7-5.9) after diagnosis. Patients received a median cumulative dose of 168 mg/kg (IQR 157-197) body weight. Relapse-free survival was 65%, 44%, 27% and 13% after 6 months, 1 year, 2 years and 5 years, respectively. In multivariate analysis, sustained remission >2 years was associated with age at treatment >5 years (P = 0.02) and cumulative dose of CYP >170 mg/kg (P = 0.02). Frequently relapsing versus steroid-dependent status and female gender were predictors of borderline significance. Height and body mass index standard deviation score were significantly influenced by CYP treatment. In our study, long-term efficacy of cyclophosphamide in steroid-responsive nephrotic syndrome is disappointing. Further well-designed trials are required to evaluate the efficacy of other steroid-sparing agents.
    Nephrology Dialysis Transplantation 01/2011; 26(1):178-84. · 3.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Primary hyperoxalurias are rare recessive inherited inborn errors of glyoxylate metabolism. They are responsible for progressive renal involvement, which further lead to systemic oxalate deposition, which can even occur in infants. Primary hyperoxaluria type 1 is the most common form in Europe and is due to alanine-glyoxylate aminostransferase deficiency, a hepatic peroxisomal pyridoxin-dependent enzyme. Therefore primary hyperoxaluria type 1 is responsible for hyperoxaluria leading to aggressive stone formation and nephrocalcinosis. As glomerular filtration rate decreases, systemic oxalate storage occurs throughout all the body, and mainly in the skeleton. The diagnosis is first based on urine oxalate measurement, then on genotyping, which may also allow prenatal diagnosis to be proposed. Conservative measures – including hydration, crystallization inhibitors and pyridoxine – are safe and may allow long lasting renal survival, provided it is given as soon as the diagnosis has been even suspected. No dialysis procedure can remove enough oxalate to compensate oxalate overproduction from the sick liver, therefore a combined liver and kidney transplantation should be planned before advanced renal disease has occurred, in order to limit/avoid systemic oxalate deposition. In the future, primary hyperoxaluria type 1 may benefit from hepatocyte transplantation, chaperone molecules, etc.
    Nephrologie & Therapeutique - NEPHROL THER. 01/2011; 7(4):249-259.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Haemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy with acute renal failure, haemolytic anaemia with schizocytes and thrombocytopenia. Typical forms (D+ HUS) are caused by gastrointestinal infection with Escherichia coli species producing verotoxines (or Shiga toxins, STEC). It is estimated that 5–8 % of infected individuals will develop HUS following STEC infection. E. coli O157:H7 is the most commonly involved serotype and can lead to D+ HUS in 15 % of young infected children. Vehicles of STEC transmission are contaminated food (ground beef, unpasteurised dairy products, unwashed and uncooked fruit and vegetables), person-to-person transmission and contact with farm animals with STEC. After an average incubation period of 3 to 8 days, patients develop painful bloody diarrhoea followed by systemic toxinemia. This may lead to thrombotic microangiopathy with endothelial damage and activation of local thrombosis. Since 1996, the Institut de Veille Sanitaire (InVS) centralises all notified French cases of D+ HUS in children less than 15 years of age and investigates cases regrouped by time and place for the presence of STEC risk factors. The average annual incidence ranges between 0.6 and one for 100 000 children younger than 15 years and with a peak at 1 year of age. Fifty-one percent of HUS occur between June and September. Patients with a suspicion of STEC infection or bloody diarrhoea should not receive antibiotics, antimotility agents, narcotics and non-steroidal anti-inflammatory drugs. Maintenance optimal hydration provides nephroprotection. The management of HUS remains supportive. Dialysis was required for 46 % of HUS cases in 2009. For similar indication, peritoneal dialysis has to be a first choice treatment. Neurological injury is the most frequent non-renal complication and the first cause of death. Early initiation of plasmapheresis might improve the prognosis. Overall mortality rate ranges between 1 and 5 %. One third of patients suffer from long-term renal morbidity such as proteinuria, arterial hypertension and decrease of glomerular filtration rate. The longer the duration of anuria, the greater the risk of sequellae. Any patient with a history of HUS needs a long-term renal follow-up.
    Archives De Pediatrie - ARCHIVES PEDIATRIE. 01/2011; 18(7):823-830.