Publications by authors named "Isabelle Vrillon"

11 Publications

  • Page 1 of 1

Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

BMJ Open 2020 09 23;10(9):e037306. Epub 2020 Sep 23.

Department of Pediatric Nephrology, Robert Debré Hospital, APHP, Paris, France.

Introduction: Guidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg's immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects.

Methods And Analysis: We conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g).

Ethics And Dissemination: The study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications.

Trial Registration Number: NCT03560011.
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http://dx.doi.org/10.1136/bmjopen-2020-037306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513594PMC
September 2020

Temocillin dosage adjustment in a preterm infant with severe renal disease: a case report.

J Antimicrob Chemother 2020 12;75(12):3652-3655

Université de Lorraine, CHRU-Nancy, Department of Clinical Pharmacology and Toxicology, F-54000 Nancy, France.

Background: Temocillin is a carboxypenicillin antibiotic indicated in complicated urinary tract infections due to susceptible ESBL-producing Enterobacteriaceae. While temocillin therapeutic schemes for adult patients with normal or impaired renal function are evidence based, little is known in paediatric populations.

Objectives: We report herein the management of temocillin treatment in a preterm infant with end-stage renal disease.

Patients And Methods: The patient was a 7-month-old preterm infant born at 35 weeks gestation and treated by temocillin for 10 days for a bacteraemic urinary tract infection due to a susceptible ESBL-producing Enterobacter cloacae complex strain. Temocillin was administered by continuous infusion using a loading dose of 25 mg followed by a maintenance dose of 70 mg daily. Determination of MIC and temocillin plasma and urinary concentration was performed.

Results: Clinical improvement was observed 24 h after the initiation of temocillin treatment. Temocillin concentrations ranged between 21.6 and 35.5 mg/L in urine between the first and the sixth day of treatment and between 47.0 and 61.8 mg/L in plasma after 6 and 10 days of treatment, respectively. Temocillin concentrations were found to be above the determined MIC of 6 mg/L. From the measured concentrations, we can postulate that 100%fT>MIC was achieved in urine and at least equal to 40% in plasma.

Conclusions: Temocillin dosing adjustment performed in the present reported case allowed safe and effective treatment. The strategy described herein could be used as a basis for further clinical studies relative to temocillin use in a paediatric population with renal impairment.
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http://dx.doi.org/10.1093/jac/dkaa356DOI Listing
December 2020

[Vaccine recommendations for children with idiopathic nephrotic syndrome].

Nephrol Ther 2020 May 8;16(3):177-183. Epub 2020 Apr 8.

Service de médecine infantile, secteur de néphrologie pédiatrique, hôpital d'Enfants de Brabois, CHRU de Nancy, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.

The specific treatment of idiopathic nephrotic syndrome is based on corticosteroid therapy and/or steroid-sparing immunosuppressive agents in children who are steroid-dependant or frequent relapsers (60-70 %). Patients have an increased infectious risk not only related to the disease during relapses (hypogammaglobulinemia and urinary leakage of opsonins) but also to treatments (corticosteroids or immunosuppressive agents) in period of remission. Vaccination is therefore particularly recommended in these patients. Potential vaccine risks are ineffectiveness, induction of vaccine disease and relapse of idiopathic nephrotic syndrome. Only live vaccines expose to the risk of vaccine disease: they are in general contra-indicated under immunosuppressive treatment. The immunogenicity of inactivated vaccines is reduced but persists. The immunogenic stimulus of vaccination may in theory trigger a relapse of the nephrotic syndrome. Nevertheless, this risk is low in the literature, and even absent in some studies. The benefit-risk ratio is therefore in favor of vaccination with respect to the vaccination schedule for inactivated vaccines, with wide vaccination against pneumococcus and influenza annually. Depending on the context and after expert advice, immunization with live vaccines could be discussed if residual doses/levels of immunosuppressive treatments are moderate and immunity preserved.
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http://dx.doi.org/10.1016/j.nephro.2019.09.007DOI Listing
May 2020

Comparison between citrate and acetate dialysate in chronic online hemodiafiltration: A short-term prospective study in pediatric settings.

Nephrol Ther 2020 May 8;16(3):158-163. Epub 2020 Apr 8.

Service de néphrologie, dialyse et transplantation pédiatriques, Hôpital d'Enfants, CHRU de Nancy, rue du Morvan, 54500 Vandœuvre-lès-Nancy, France.

Background: The use of citrate in chronic hemodialysis to acidify dialysis solutions, in replacement of acetate, began in the 2000's. The purpose of the following study is to determine whether this change represents a better alternative regarding short-term tolerance, efficiency and biocompatibility of chronic renal replacement therapy (RRT) in pediatric patients.

Methods: A monocentric prospective observational study was conducted in the pediatric dialysis department of Nancy (France) between December 1st, 2014 and January 25, 2015 on a cohort of pediatric patients under predilution on-line hemodiafiltration (olHDF). Sessions were analysed during two study periods of 14 days: a first period during which dialysis solutions were acidified using acetate and a second during which solutes were acidified using citrate. These periods were separated by a washout period of 28 days on citrate solution. Each patient served as his own control.

Results: Dialysis clinical tolerance seems better under citrate regimen, with no statistical significance. No benefit was brought out regarding the prevention of coagulation accidents in the extracorporeal circuit under citrate regimen. The efficiency of olHDF sessions was similar between periods, both in terms of uremic toxins clearance and medium-molecular-weight molecules (MMWM) removal. The evolution of several biological parameters seemed favourable over the citrate period: increase in pre-dialysis serum bicarbonate, stability of plasma hemoglobin and decrease in erythropoietin resistance index (ERI). However, differences in the variation of these parameters between the two periods were not significant. No severe and/or symptomatic hypocalcemia occurred.

Conclusion: The use of citrate instead of acetate in dialysis and substitution solutions appears in the short term as a safe alternative for chronic online hemodiafiltration in children.
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http://dx.doi.org/10.1016/j.nephro.2019.12.002DOI Listing
May 2020

School level of children carrying a HNF1B variant or a deletion.

Eur J Hum Genet 2020 01 3;28(1):56-63. Epub 2019 Sep 3.

Service de Pédiatrie, CHU de Limoges, Limoges, France.

The prevalence of neurological involvement in patients with a deletion of or a variant in the HNF1B gene remains discussed. The aim of this study was to investigate the neuropsychological outcomes in a large cohort of children carrying either a HNF1B whole-gene deletion or a disease-associated variant, revealed by the presence of kidney anomalies. The neuropsychological development-based on school level-of 223 children included in this prospective cohort was studied. Data from 180 children were available for analysis. Patients mean age was 9.6 years, with 39.9% of girls. Among these patients, 119 carried a HNF1B deletion and 61 a disease-associated variant. In the school-aged population, 12.7 and 3.6% of patients carrying a HNF1B deletion and a disease-associated variant had special educational needs, respectively. Therefore, the presence of a HNF1B deletion increases the risk to present with a neuropsychiatric involvement when compared with the general population. On the other hand, almost 90% of patients carrying a HNF1B disease-associated variant or deletion have a normal schooling in a general educational environment. Even if these findings do not predict the risk of neuropsychiatric disease at adulthood, most patients diagnosed secondary to kidney anomalies do not show a neurological outcome severe enough to impede standard schooling at elementary school. These results should be taken into account in prenatal counseling.
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http://dx.doi.org/10.1038/s41431-019-0490-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906503PMC
January 2020

Quality of life in adolescents with chronic kidney disease who initiate haemodialysis treatment.

BMC Nephrol 2019 05 14;20(1):163. Epub 2019 May 14.

Aix-Marseille Univ, School of medicine - La Timone Medical Campus, EA 3279: - CEReSS Health Service Research and Quality of Life Center, Marseille, France.

Background: To describe the quality of life of adolescents initiating haemodialysis, to determine the factors associated with quality of life, and to assess coping strategies and their impact on quality of life.

Methods: All adolescents initiating haemodialysis between September 2013 and July 2015 in French paediatric haemodialysis centres were included. Quality of life data were collected using the "Vécu et Santé Perçue de l'Adolescent et l'Enfant" questionnaire, and coping data were collected using the Kidcope questionnaire. Adolescent's quality of life was compared with age- and sex-matched French control.

Results: Thirty-two adolescents were included. Their mean age was 13.9 ± 2.0 years. The quality of life score was lowest in leisure activities and highest in relationships with medical staff. Compared with the French control, index, energy-vitality, relationships with friends, leisure activities and physical well-being scores were significantly lower in haemodialysis population. In multivariate analyses, active coping was positively associated with quality of life and especially with energy-vitality, relationships with parents and teachers, and school performance. In contrast, avoidant and negative coping were negatively associated with energy-vitality, psychological well-being and body image for avoidant coping, and body image and relationships with medical staff for negative coping.

Conclusions: The quality of life of haemodialysis adolescents, and mainly the dimensions of leisure activities, physical well-being, relationships with friends and energy-vitality, were significantly altered compared to that of the French population. The impact of coping strategies on quality of life seems to be important. Given the importance of quality of life and coping strategies in adolescents with chronic disease, health care professionals should integrate these aspects into care management.
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http://dx.doi.org/10.1186/s12882-019-1365-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515621PMC
May 2019

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

Nephrol Dial Transplant 2019 11;34(11):1932-1940

Department of Pediatric Nephrology, Gazi University, Ankara, Turkey.

Background: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment.

Methods: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias.

Results: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings.

Conclusions: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.
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http://dx.doi.org/10.1093/ndt/gfz069DOI Listing
November 2019

Patient and transplant outcome in infants starting renal replacement therapy before 2 years of age.

Nephrol Dial Transplant 2018 08;33(8):1459-1465

Pediatric Nephrology Department, Robert Debré University Hospital, APHP, Paris, France.

Background: Despite major technical improvements in the care of children requiring renal replacement therapy (RRT) before 2 years of age, the management of those patients remains challenging and transplantation is generally delayed until the child weighs 10 kg or is 2 years old. In this national cohort study, we studied patient and graft survival in children starting RRT before 2 years of age to help clinicians and parents when deciding on RRT initiation and transplantation management.

Methods: All children starting RRT before 24 months of age between 1992 and 2012 in France were included through the national Renal Epidemiology and Information Network (REIN) registry. The primary endpoints were patient survival on dialysis and 10-year graft survival.

Results: A total of 224 patients were included {62% boys, median age 10.5 months [interquartile range (IQR) 5.8-15.6]}. The 10-year survival rate was 84% (IQR 77-89). Suffering from extrarenal comorbidities was the only factor significantly associated with both an increased risk of death on dialysis [hazard ratio 5.9 (95% confidence interval 1.8-19.3)] and a decreased probability of being transplanted. During follow-up, 174 renal transplantations were performed in 171 patients [median age at first transplantation 30.2 (IQR 21.8-40.7) months]. The 10-year graft survival was 74% (IQR 67-81). Factors associated with graft loss in multivariate analysis were the time spent on dialysis before transplantation, donor/recipient height ratio with an increased risk for both small and tall donors and presenting two human leucocyte antigen-antigen D-related mismatches.

Conclusions: This study confirms the good outcome of children starting RRT before 2 years of age. The main question remains when and how to transplant those children. Our study provides data on the optimal morphological and immunological matching in order to help clinicians in their decisions.
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http://dx.doi.org/10.1093/ndt/gfy040DOI Listing
August 2018

Prevalence of Novel Mutations in Antenatal Bartter Syndrome.

Clin J Am Soc Nephrol 2018 02 16;13(2):242-250. Epub 2017 Nov 16.

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Background And Objectives: Mutations in the gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome.

Design, Setting, Participants, & Measurements: The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause (=42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases.

Results: We detected mutations in in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases.

Conclusions: mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome.
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http://dx.doi.org/10.2215/CJN.05670517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967426PMC
February 2018

Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

J Am Soc Nephrol 2017 Aug 5;28(8):2540-2552. Epub 2017 Apr 5.

Department of Genetics and.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with mutations. Functional analyses were performed in oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.
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http://dx.doi.org/10.1681/ASN.2016101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533235PMC
August 2017

Effect of center practices on the choice of the first dialysis modality for children and young adults.

Pediatr Nephrol 2017 04 14;32(4):659-667. Epub 2016 Nov 14.

REIN Registry, Agence de la biomédecine, Saint-Denis, La Plaine, France.

Background: Peritoneal dialysis (PD) remains the modality of choice in children, but there is no clear evidence to support a better outcome in children treated with PD. We aimed to assess factors that have an impact on the choice of dialysis modality in children and young adults in France and sought to determine the roles of medical factors and center practices.

Methods: We included all patients aged <20 years at the start of renal replacement therapy (RRT), recorded in the French RRT Registry between 2002 and 2013. Hierarchical logistic regression models were used to study the association between the patient/center characteristics and the probability of receiving PD as the first dialysis modality.

Results: We included 806 patients starting RRT in 177 centers, 23 of which were specialized pediatric centers. Six hundred and one patients (74.6 %) started with hemodialysis (HD), whereas 205 (25.4 %) started with PD. A greater probability of PD was found in younger children, whereas starting the treatment in an emergency setting was associated with a low use of PD. We found a significant variability among centers that accounted for 43 % of the total variability. The probability of PD was higher in adult centers and was proportional to the rate of PD in the center.

Conclusions: Center practices are a major factor in the choice of dialysis modality. This raises concerns about patient and family choices and to what extent doctors may influence the final decision. Further pediatric studies focusing on children's and parents' wishes are needed to provide care as close as possible to patients' and families' expectations.
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http://dx.doi.org/10.1007/s00467-016-3538-7DOI Listing
April 2017