Publications by authors named "Veronique Baudouin"

74 Publications

Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis.

Pediatr Nephrol 2021 Feb 26. Epub 2021 Feb 26.

Advicenne, Nîmes, France.

Background: A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months.

Methods: Thirty pediatric and adult patients were included in an open-label extension study after a phase II/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored.

Results: There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69-86% and 83-93% of patients. Overall adherence rates were ≥ 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study.

Conclusions: Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable.

Trial Registration Number: Registered as EudraCT 2013-003828-36 on the 3rd of September 2013.
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http://dx.doi.org/10.1007/s00467-020-04873-0DOI Listing
February 2021

COVID-19 in children treated with immunosuppressive medication for kidney diseases.

Arch Dis Child 2020 Dec 21. Epub 2020 Dec 21.

Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Background: Children are recognised as at lower risk of severe COVID-19 compared with adults, but the impact of immunosuppression is yet to be determined. This study aims to describe the clinical course of COVID-19 in children with kidney disease taking immunosuppressive medication and to assess disease severity.

Methods: Cross-sectional study hosted by the European Rare Kidney Disease Reference Network and supported by the European, Asian and International paediatric nephrology societies. Anonymised data were submitted online for any child (age <20 years) with COVID-19 taking immunosuppressive medication for a kidney condition. Study recruited for 16 weeks from 15 March 2020 to 05 July 2020. The primary outcome was severity of COVID-19.

Results: 113 children were reported in this study from 30 different countries. Median age: 13 years (49% male). Main underlying reasons for immunosuppressive therapy: kidney transplant (47%), nephrotic syndrome (27%), systemic lupus erythematosus (10%). Immunosuppressive medications used include: glucocorticoids (76%), mycophenolate mofetil (MMF) (54%), tacrolimus/ciclosporine A (58%), rituximab/ofatumumab (11%). 78% required no respiratory support during COVID-19 illness, 5% required bi-level positive airway pressure or ventilation. Four children died; all deaths reported were from low-income countries with associated comorbidities. There was no significant difference in severity of COVID-19 based on gender, dialysis status, underlying kidney condition, and type or number of immunosuppressive medications.

Conclusions: This global study shows most children with a kidney disease taking immunosuppressive medication have mild disease with SARS-CoV-2 infection. We therefore suggest that children on immunosuppressive therapy should not be more strictly isolated than children who are not on immunosuppressive therapy.
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http://dx.doi.org/10.1136/archdischild-2020-320616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754669PMC
December 2020

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

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Kidney Int 2021 Mar 1;99(3):737-749. Epub 2020 Aug 1.

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France; Université Toulouse III Paul-Sabatier, Toulouse, France. Electronic address:

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-β4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.
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http://dx.doi.org/10.1016/j.kint.2020.06.043DOI Listing
March 2021

Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments.

Pediatr Nephrol 2021 Jan 26;36(1):83-91. Epub 2020 Jul 26.

Advicenne, Nîmes, France.

Background: Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme.

Methods: In a multicenter, open-label, non-inferiority trial (n = 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety.

Results: When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (p < 0.0001, per protocol), as was statistical superiority (p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p < 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of - 14.2 [- 25.9, - 2.6] mm) with ADV7103.

Conclusions: Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA.

Trial Registration: Registered as EudraCT 2013-002988-25 on the 1st July 2013 Graphical abstract.
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http://dx.doi.org/10.1007/s00467-020-04693-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701073PMC
January 2021

[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

Nocturnal enteral nutrition is therapeutic for growth failure in Fanconi-Bickel syndrome.

J Inherit Metab Dis 2020 05 1;43(3):540-548. Epub 2020 Jan 1.

Reference Centre for Inborn Errors of Metabolism, Robert-Debré University Hospital, Paris, France.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterised by impaired glucose liver homeostasis and proximal renal tubular dysfunction. It is caused by pathogenic variants in SLC2A2 coding for the glucose transporter GLUT2. Main clinical features include hepatomegaly, fasting hypoglycaemia, postprandial hyperglycaemia, Fanconi-type tubulopathy occasionally with rickets, and a severe growth disorder. While treatment for renal tubular dysfunction is well established, data regarding optimal nutritional therapy are scarce. Similarly, detailed clinical evaluation of treated FBS patients is lacking. These unmet needs were an incentive to conduct the present pilot study. We present clinical findings, laboratory parameters and molecular genetic data on 11 FBS patients with emphasis on clinical outcome under various nutritional interventions. At diagnosis, the patients' phenotypic severity could be classified into two categories: a first group with severe growth failure and rickets, and a second group with milder signs and symptoms. Three patients were diagnosed early and treated because of family history. All patients exhibited massive glucosuria at diagnosis and some in both groups had fasting hypoglycaemic episodes. Growth retardation improved drastically in all five patients treated by intensive nutritional intervention (nocturnal enteral nutrition) and uncooked cornstarch with final growth parameters in the normal range. The four severely affected patients who were treated with uncooked cornstarch alone did not catch up growth. All patients received electrolytes and l-carnitine supplementation to compensate for the tubulopathy. This is one of the largest series of FBS on therapeutic management with evidence that nocturnal enteral nutrition rescues growth failure.
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http://dx.doi.org/10.1002/jimd.12203DOI Listing
May 2020

Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function.

J Clin Invest 2020 01;130(1):335-344

Laboratory of Epithelial Biology and Disease and.

BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).
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http://dx.doi.org/10.1172/JCI129937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934218PMC
January 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

Control of TLR7-mediated type I IFN signaling in pDCs through CXCR4 engagement-A new target for lupus treatment.

Sci Adv 2019 07 10;5(7):eaav9019. Epub 2019 Jul 10.

CNRS UMR-8601, CICB, 45 rue des Saints-Pères, 75006 Paris, France.

Type I interferons are highly potent cytokines essential for self-protection against tumors and infections. Deregulations of type I interferon signaling are associated with multiple diseases that require novel therapeutic options. Here, we identified the small molecule, IT1t, a previously described CXCR4 ligand, as a highly potent inhibitor of Toll-like receptor 7 (TLR7)-mediated inflammation. IT1t inhibits chemical (R848) and natural (HIV) TLR7-mediated inflammation in purified human plasmacytoid dendritic cells from blood and human tonsils. In a TLR7-dependent lupus-like model, in vivo treatment of mice with IT1t drives drastic reduction of both systemic inflammation and anti-double-stranded DNA autoantibodies and prevents glomerulonephritis. Furthermore, IT1t controls inflammation, including interferon α secretion, in resting and stimulated cells from patients with systemic lupus erythematosus. Our findings highlight a groundbreaking immunoregulatory property of CXCR4 signaling that opens new therapeutic perspectives in inflammatory settings and autoimmune diseases.
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http://dx.doi.org/10.1126/sciadv.aav9019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620093PMC
July 2019

Voiding cystography: an unusual route of induced hypothyroidism by iodine overdose in two newborns with chronic kidney disease.

Pediatr Nephrol 2019 07 1;34(7):1295-1297. Epub 2019 Apr 1.

Pediatric Nephrology Unit, Robert Debré University Hospital - APHP, Paris, France.

Background: Iatrogenic induced hypothyroidism had been described in newborns and more particularly in preterm infants after cutaneous or intravenous exposure to iodine. CASE-DIAGNOSIS : We reported a new risk of iodine intoxication with the cases of two newborns who developed hypothyroidism after intra vesical iodine injection during a cystography, which was performed to confirm antenatal diagnosis of posterior urethral valves (PUV). The newborns both developed transient hypothyroidism due to an iodine overdose.

Conclusions: These two observations suggest that voiding cystourethrography (VCUG) should be carefully considered in newborns with severe uropathy, particularly in the case of renal insufficiency. If indicated, thyroid function should be monitored in the following weeks, and in case of hypothyroidism treatment should be started.
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http://dx.doi.org/10.1007/s00467-019-04247-1DOI Listing
July 2019

Effect of nonsteroidal anti-inflammatory drugs in children with Bartter syndrome.

Pediatr Nephrol 2019 04 13;34(4):679-684. Epub 2018 Nov 13.

Pediatric Nephrology Department, Robert Debre University Hospital, APHP, 48, Bd Serurier, 75019, Paris, France.

Background: Bartter syndrome (BS) is a salt-wasting tubulopathy with induced expression of cyclooxygenase-2 in the macula densa, leading to increased prostaglandin production and hyperreninemia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently used in BS; however, there is limited information on the impact of NSAIDs at treatment initiation or the potential utility of plasma renin level to guide therapy in patients with BS.

Methods: We included 19 patients with BS treated with NSAIDs between 1994 and 2016. We assessed serum levels of renin, aldosterone, electrolytes, calcium, phosphorus, vitamin D, and intact parathyroid hormone (iPTH) before and after treatment initiation. We also recorded modifications in sodium and potassium supplements and changes in urine calcium.

Results: Median age at diagnosis was 0.9 months [IQR 0-6.9]. Seven patients had BS types 1 or 2, 12 had BS type 3 and two had no mutation identified. There was a trend towards a decrease in sodium chloride supplementation after initiation of NSAIDs. When defining response to treatment based on the normalization of plasma renin level, responders had a greater reduction in their electrolytes supplementation. NSAIDs treatment was associated with a reduction in urine calcium. Before treatment, half of the patients had elevated iPTH, but iPTH normalized following initiation of NSAIDs in all but one patient.

Conclusions: This study confirms that NSAIDs reduce urine wasting of sodium and calcium in patients with BS. Monitoring serum renin levels may be useful to identify the lowest effective dose of NSAIDs that optimizes reduction of urine electrolyte losses.
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http://dx.doi.org/10.1007/s00467-018-4135-8DOI Listing
April 2019

Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome.

Pediatr Nephrol 2019 02 14;34(2):253-259. Epub 2018 Aug 14.

Pediatric Nephrology Department, Robert-Debré Hospital, APHP, 48 bld Sérurier, 75019, Paris, France.

Background: Several studies have demonstrated that rituximab (RTX) improves relapse-free survival in patients with steroid-dependent nephrotic syndrome (SDNS). However, these studies used various RTX regimens and there are few data comparing these regimens in children with SDNS. In this retrospective study, we assessed the effect of three different initial RTX regimens on both time to B cell reconstitution and to first relapse.

Methods: Sixty-one SDNS patients receiving a first course of RTX were included. Group 1 received one injection of 100 mg/m, group 2 received one injection of 375 mg/m, and group 3 received two injections of 375 mg/m at day 0 and day 7. Time to B cell reconstitution and time to first relapse and respective risk factors were studied.

Results: Median time to B cell reconstitution was 2.5 [1.8-3.5], 5.0 [3.9-6.0], and 6.6 [4.6-7.8] months in groups 1, 2, and 3, respectively. RTX regimen was associated with time to B cell reconstitution (HRs group 2 vs. 3, 4.07 [1.96-8.48]; group 1 vs. 3, 11.13 [4.04-30.67]). One-year relapse-free survival was 50% [58-77], 59% [42-76], and 72% [46-87] in groups 1, 2, and 3, respectively. RTX regimen was associated with risk of relapse (HRs group 2 vs. 3, 1.55 [0.51-4.65]; group 1 vs. 3, 4.98 [1.15-21.60]).

Conclusions: The initial dose of rituximab impacts time to B cell reconstitution and the probability of relapse. Risk of relapse is also associated with patient characteristics, suggesting that RTX regimen could be modified for each patient to balance efficacy, cost, and side effects.
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http://dx.doi.org/10.1007/s00467-018-4052-xDOI Listing
February 2019

Treatment and outcome of congenital nephrotic syndrome.

Nephrol Dial Transplant 2019 03;34(3):458-467

Hôpital Necker-Enfants malades, Néphrologie pédiatrique, Assistance Publique des Hôpitaux de Paris, Université Paris Descartes-Sorbonne Paris-Cité, Paris, France.

Background: Recommendations for management of Finnish-type congenital nephrotic syndrome (CNS) followed by many teams include daily albumin infusions, early bilateral nephrectomy, dialysis and transplantation. We aimed to assess the treatment and outcome of patients with CNS in France.

Methods: We conducted a nationwide retrospective study on 55 consecutive children born between 2000 and 2014 treated for non-infectious CNS.

Results: The estimated cumulative incidence of CNS was 0.5/100 000 live births. The underlying defect was biallelic mutations in NPHS1 (36/55, 65%), NPHS2 (5/55, 7%), PLCE1 (1/55, 2%), heterozygous mutation in WT1 (4/55, 7%) and not identified in nine children (16%). Fifty-three patients (96%) received daily albumin infusions from diagnosis (median age 14 days), which were spaced and withdrawn in 10 patients. Twenty children (35%) were managed as outpatients. Thirty-nine patients reached end-stage kidney disease (ESKD) at a median age of 11 months. The overall renal survival was 64% and 45% at 1 and 2 years of age, respectively. Thirteen children died during the study period including four at diagnosis, two of nosocomial catheter-related septic shock, six on dialysis and one after transplantation. The remaining 13 patients were alive with normal renal function at last follow-up [median 32 months (range 9-52)]. Renal and patient survivals were longer in patients with NPHS1 mutations than in other patients. The invasive infection rate was 2.41/patient/year.

Conclusions: Our study shows: (i) a survival free from ESKD in two-thirds of patients at 1 year and in one-half at 2 years and (ii) a significant reduction or even a discontinuation of albumin infusions allowing ambulatory care in a subset of patients. These results highlight the need for new therapeutic guidelines for CNS patients.
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http://dx.doi.org/10.1093/ndt/gfy015DOI Listing
March 2019

Patterns of Clinical Response to Eculizumab in Patients With C3 Glomerulopathy.

Am J Kidney Dis 2018 07 9;72(1):84-92. Epub 2018 Feb 9.

Department of Nephrology and Immunology, Centre Hospitalier Universitaire de Nantes, Nantes, France. Electronic address:

Background: Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy of eculizumab.

Study Design: Case series of C3 glomerulopathy.

Setting & Participants: Pediatric and adult patients with C3 glomerulopathy treated with eculizumab between 2010 and 2016 were identified through the C3 glomerulopathy French registry database, and a questionnaire was sent to participating French pediatric and adult nephrology centers, as well as one pediatric referral center in Québec, Canada.

Outcomes: Global or partial clinical renal response.

Measurements: Evolution of serum creatinine and proteinuria values.

Results: 26 patients (13 children/adolescents) were included. 22 (85%) patients had received steroids, plasma exchange, or immunosuppressive therapy before eculizumab, and 3 of them had rapid progression of their kidney disease despite treatment. At the initiation of eculizumab therapy, 11 (42%) patients had chronic kidney disease, 7 (27%) had rapidly progressive disease, and 3 (12%) required dialysis. After eculizumab treatment (median duration, 14 months), 6 (23%) patients had a global clinical response; 6 (23%), a partial clinical response; and 14 (54%), no response. Compared with those who had a partial clinical or no response, patients who had a global clinical response had lower estimated glomerular filtration rates, a more rapidly progressive course, and more extracapillary proliferation on kidney biopsy. Age, extent of renal fibrosis, frequency of nephrotic syndrome, low serum C3 and C3 nephritic factor and elevated soluble C5b-9 concentrations, or complement gene variants did not differ between responders and nonresponders.

Limitations: Retrospective design without a control group, relatively small number of cases, inclusion of pediatric and adult cases.

Conclusions: Eculizumab appears to be a potential treatment for patients with crescentic rapidly progressive C3 glomerulopathy. Its benefit in patients with non-rapidly progressing forms seems to be limited.
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http://dx.doi.org/10.1053/j.ajkd.2017.11.019DOI Listing
July 2018

Severe neonatal hypertension revealing arterial tortuosity syndrome.

Kidney Int 2018 02;93(2):526

Pediatric Nephrology Department, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.kint.2017.09.007DOI Listing
February 2018

Adverse Events under Tacrolimus and Cyclosporine in the First 3 Years Post-Renal Transplantation in Children.

Clin Drug Investig 2018 Feb;38(2):157-171

Department of Paediatric Pharmacology and Pharmacogenetics, Hospital Robert Debré, APHP, 48 Boulevard Sérurier, 75019, Paris, France.

Background: Progress in immunosuppression has reduced acute rejection, graft loss and mortality after renal transplantation. Adverse drug reactions are well described in adults but few data are available in children. Our objectives were to analyse the adverse events reported in the first 3 years post-transplantation in children receiving tacrolimus or cyclosporine-based immunosuppression and compare them with the information of the Summary of Product Characteristics.

Methods: This retrospective study included all children who underwent a renal transplant at Hospital Robert Debré between 2002 and 2015. Initial immunosuppression was based on induction, calcineurin inhibitor, mycophenolate mofetil and corticosteroids. Adverse events were collected from medical records and coded using the Medical Dictionary for Regulatory Activities and the implications of tacrolimus and cyclosporine analysed. Statistical analyses were performed using SAS 9.4.

Results: One hundred and twenty-five children were included. During the observation period [2.7 years (0.6-4.3)], 105 patients received tacrolimus and 39 received cyclosporine. The incidence rate for gastrointestinal disorders was 0.128 and 0.056 by patient-years of exposure (p < 0.05), under tacrolimus and cyclosporine schedules. For neutropenia, it was 0.064 and 0.014 (p < 0.05). The frequencies of toxic nephropathy and gastrointestinal pain were higher than those in the Summary of Product Characteristics of tacrolimus (> 20%) and cyclosporine (> 10%). Cosmetic events for cyclosporine and neutropenia for tacrolimus were frequently observed (18 and 14.3%, respectively), although uncommon in the Summary of Product Characteristics.

Conclusions: The exposure-adjusted incidence rate of gastrointestinal disorders and neutropenia was higher in children under the tacrolimus schedule. Our findings contribute to the evaluation of the benefit-risk balance of immunosuppressive therapy following paediatric renal transplantation.
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http://dx.doi.org/10.1007/s40261-017-0594-0DOI Listing
February 2018

Functional characterization of tektin-1 in motile cilia and evidence for TEKT1 as a new candidate gene for motile ciliopathies.

Hum Mol Genet 2018 01;27(2):266-282

INSERM UMR 1163, Laboratory of Hereditary Kidney Diseases, 75015 Paris, France.

A child presenting with Mainzer-Saldino syndrome (MZSDS), characterized by renal, retinal and skeletal involvements, was also diagnosed with lung infections and airway ciliary dyskinesia. These manifestations suggested dysfunction of both primary and motile cilia, respectively. Targeted exome sequencing identified biallelic mutations in WDR19, encoding an IFT-A subunit previously associated with MZSDS-related chondrodysplasia, Jeune asphyxiating thoracic dysplasia and cranioectodermal dysplasia, linked to primary cilia dysfunction, and in TEKT1 which encodes tektin-1 an uncharacterized member of the tektin family, mutations of which may cause ciliary dyskinesia. Tektin-1 localizes at the centrosome in cycling cells, at basal bodies of both primary and motile cilia and to the axoneme of motile cilia in airway cells. The identified mutations impaired these localizations. In addition, airway cells from the affected individual showed severe motility defects without major ultrastructural changes. Knockdown of tekt1 in zebrafish resulted in phenotypes consistent with a function for tektin-1 in ciliary motility, which was confirmed by live imaging. Finally, experiments in the zebrafish also revealed a synergistic effect of tekt1 and wdr19. Altogether, our data show genetic interactions between WDR19 and TEKT1 likely contributing to the overall clinical phenotype observed in the affected individual and provide strong evidence for TEKT1 as a new candidate gene for primary ciliary dyskinesia.
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http://dx.doi.org/10.1093/hmg/ddx396DOI Listing
January 2018

Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

Pediatr Nephrol 2018 03 23;33(3):473-483. Epub 2017 Oct 23.

INSERM UMR1163, Laboratory of Hereditary Kidney Diseases, Imagine Institute, 24 Boulevard du Montparnasse, 75015, Paris, France.

Background: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease.

Methods: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort.

Results: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing.

Conclusions: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.
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http://dx.doi.org/10.1007/s00467-017-3819-9DOI Listing
March 2018

Bayesian treatment comparison using parametric mixture priors computed from elicited histograms.

Stat Methods Med Res 2019 02 5;28(2):404-418. Epub 2017 Sep 5.

2 UMRS 1138, CRC, INSERM, University Paris 5, University Paris 6, France.

A Bayesian methodology is proposed for constructing a parametric prior on two treatment effect parameters, based on graphical information elicited from a group of expert physicians. The motivating application is a 70-patient randomized trial to compare two treatments for idiopathic nephrotic syndrome in children. The methodology relies on histograms of the treatment parameters constructed manually by each physician, applying the method of Johnson et al. (2010). For each physician, a marginal prior for each treatment parameter characterized by location and precision hyperparameters is fit to the elicited histogram. A bivariate prior is obtained by averaging the marginals over a latent physician effect distribution. An overall prior is constructed as a mixture of the individual physicians' priors. A simulation study evaluating several versions of the methodology is presented. A framework is given for performing a sensitivity analysis of posterior inferences to prior location and precision and illustrated based on the idiopathic nephrotic syndrome trial.
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http://dx.doi.org/10.1177/0962280217726803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658278PMC
February 2019

Combination therapy of rituximab and mycophenolate mofetil in childhood lupus nephritis.

Pediatr Nephrol 2018 Jan 5;33(1):111-116. Epub 2017 Aug 5.

Pediatric Nephrology Department, Robert Debré Hospital, Assistance publique-Hôpitaux de Paris (APHP), Paris, France.

Background: In clinical trials, the addition of rituximab (RTX) to the combination therapeutic regimen of mycophenolate mofetil (MMF) and corticosteroids failed to improve outcome in lupus nephritis (LN). However, recent data suggest that RTX may have steroid-sparing beneficial effects with an efficacy similar to that of conventional regimens. We report our experience with RTX in the treatment of children with LN.

Methods: Patients treated with RTX for first occurrence of LN class III to V were enrolled in the study. Treatment consisted of methylprednisolone pulse (500 mg/m) followed by RTX (1000 mg/1.73 m) at days 1 and 15, and MMF (1200 mg/m/day). Prednisolone tapering and withdrawal was left to the physician's discretion. Complete remission (CR) was defined as a urine protein-to-creatinine ratio (U Pr/Cr) of <5 mg/mg and normal serum creatinine, and partial remission (PR) as a U Pr/Cr of <30 mg/mg and a <15% rise in serum creatinine over baseline.

Results: Twelve patients were included in the study, with median follow-up of 23.7 [interquartile range (IQR) 12.8-33.5] months. Median age of the patients was 13.6 [12.3-15.1] years, median proteinuria was 32 [19-67] mg/mg and median estimated glomerular filtration rate was 76.1 [59.3-97.7] mL/min/1.73 m. Median CD20 depletion duration was 10 [6.8-11.0] months. Prednisolone was rapidly tapered, with median dose of 0.3 [0.15-0.41], 0.10 [0.09-0.16] and 0.0 [0.0-0.04] mg/kg/day at 3, 6 and 12 months respectively. At 3 months, three and seven patients achieved CR and PR, respectively; at 6 and 12 months all patients achieved remission (9 CR, 3 PR) and none relapsed during follow-up. Five infectious complications were observed, including three varicella-zoster virus (VZV) infections.

Conclusions: In our pediatric patients with LN, therapy with RTX + MMF combined with a rapid decrease in steroid appears to have been an efficacious treatment for severe LN but was associated with high rate of VZV infection. The potential of RTX to allow complete steroid avoidance warrants further investigation in children.
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http://dx.doi.org/10.1007/s00467-017-3767-4DOI Listing
January 2018

Age-Dependent Risk of Graft Failure in Young Kidney Transplant Recipients.

Transplantation 2017 06;101(6):1327-1335

1 University of Bordeaux, ISPED, Centre INSERM U1219-Bordeaux Population Health Research, Bordeaux, France. 2 INSERM, ISPED, Centre INSERM U1219-Bordeaux Population Health Research, Bordeaux, France. 3 Agence de la Biomédecine, La Plaine-Saint Denis, France. 4 Pediatric Nephrology Unit, Robert Debré University Hospital, Paris, France. 5 Pediatric Nephrology Unit, Necker Enfants-Malades University Hospital, Paris, France. 6 Pediatric Nephrology Unit, Femme-Mère-Enfant Hospital, Lyon University Hospital, Lyon, France. 7 Pediatric Nephrology Unit, Jeanne de Flandre Hospital, Lille University Hospital, Lille, France. 8 Pediatric Nephrology Unit, Femme-Enfant-Adolescent Hospital, Nantes University Hospital, Nantes, France. 9 Pediatric Nephrology Unit, La Timone Hospital, Marseille University Hospital, Marseille, France. 10 Pediatric Nephrology Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France. 11 Pediatric Nephrology Unit, American Memorial Hospital, Reims University Hospital, Reims, France. 12 INSERM, Clinical Investigation Center, Clinical Epidemiology, Bordeaux, France. 13 Pediatric Nephrology Unit, Pellegrin-Enfants Hospital, Bordeaux University Hospital, Bordeaux, France.

Background: The risk of graft failure in young kidney transplant recipients has been found to increase during adolescence and early adulthood. However, this question has not been addressed outside the United States so far. Our objective was to investigate whether the hazard of graft failure also increases during this age period in France irrespective of age at transplantation.

Methods: Data of all first kidney transplantation performed before 30 years of age between 1993 and 2012 were extracted from the French kidney transplant database. The hazard of graft failure was estimated at each current age using a 2-stage modelling approach that accounted for both age at transplantation and time since transplantation. Hazard ratios comparing the risk of graft failure during adolescence or early adulthood to other periods were estimated from time-dependent Cox models.

Results: A total of 5983 renal transplant recipients were included. The risk of graft failure was found to increase around the age of 13 years until the age of 21 years, and decrease thereafter. Results from the Cox model indicated that the hazard of graft failure during the age period 13 to 23 years was almost twice as high as than during the age period 0 to 12 years, and 25% higher than after 23 years.

Conclusions: Among first kidney transplant recipients younger than 30 years in France, those currently in adolescence or early adulthood have the highest risk of graft failure.
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http://dx.doi.org/10.1097/TP.0000000000001372DOI Listing
June 2017

Observations of a large Dent disease cohort.

Kidney Int 2016 08 22;90(2):430-439. Epub 2016 Jun 22.

INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France; Reference Centre of Hereditary Renal Disease of the Child and Adult (MARHEA), Paris, France; Assistance Publique-Hôpitaux de Paris, European Georges Pompidou University Hospital, Genetics Department, Paris, France.

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.
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http://dx.doi.org/10.1016/j.kint.2016.04.022DOI Listing
August 2016

Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome.

Pediatr Nephrol 2016 11 4;31(11):2095-101. Epub 2016 Jun 4.

Department of Pediatric Nephrology, Hôpital Robert Debré, APHP, 48 Boulevard Sérurier, 75935, Paris, Cedex 19, France.

Background: Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments.

Methods: We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3-6) after the onset of MMF treatment. The characteristics of responder patients (n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n = 22) were compared by univariate analysis and multivariate logistic regression.

Results: Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8-30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01).

Conclusions: MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug.
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http://dx.doi.org/10.1007/s00467-016-3400-yDOI Listing
November 2016

Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences.

J Clin Endocrinol Metab 2016 05 10;101(5):2185-95. Epub 2016 Mar 10.

Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou (R.V.-P., L.M.-H., C.Tra., C.Sim., C.Tre., X.J.), Service de Génétique, Paris, France; INSERM, UMR970 (R.V.-P., L.M.-H., C.Tre., S.R.K., X.J.), Paris-Centre de Recherche Cardiovasculaire, Paris, France; Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (R.V.-P., J.-P.B., V.B., M.-A.M., X.J., P.H.), Paris, France; Faculté de Médecine (L.M.-H., S.Bar., J.-P.B., X.J., P.H.), Université Paris Descartes, Paris, France; Département de Physiologie (S.Bar., J.-P.B., G.M., P.H.), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France; Service de Néphrologie (V.B., M.-A.M.), Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; Service d'Endocrinologie (S.Bel.), Centre Hospitalier de Vienne, Vienne, France; Département de Pédiatrie (F.B.), Centre Hospitalier Universitaire de Rouen, Rouen, France; Service de Pédiatrie (O.C., D.R.), Centre Hospitalier de Niort, Niort, France; Département de Néphrologie (S.C.), Centre Hospitalier Universitaire de Tours, Tours, France; Département de Rhumatologie A (C.C.), Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France; Service d'endocrinologie (X.D.), Centre hospitalier Felix Guyon, St Denis de la Réunion, France; Service de Médicine Interne (E.D.), Centre Hospitalier Henri Mondor d'Aurillac, Aurillac, France; Service d'Endocrinologie (C.D.), Centre Hospitalier de Perpignan, Perpignan, France; Département de Physiologie (J.-P.H.), Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Paris, France; Département d'Endocrinologie (J.-M.K.), Centre Hospitalier Universitaire de Rouen, Rouen, France; Service d'Endocrinologie (G.L.), Centre Hospitalier de Niort, Niort, France; Assistance Publique-Hôpitaux de Paris, Service d'Endocrinologie Pédiatrique (A.L.), Hôpital Kremlin Bicêtre, Le Kremlin-Bicêtre, France; Service d'Endocrinologie

Context: Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous condition resembling primary hyperparathyroidism (PHPT) but not curable by surgery; FHH types 1, 2, and 3 are due to loss-of-function mutations of the CASR, GNA11, or AP2S1 genes, respectively.

Objective: This study aimed to compare the phenotypes of patients with genetically proven FHH types 1 or 3 or PHPT.

Design, Setting, And Patients: This was a mutation analysis in a large cohort, a cross-sectional comparison of 52 patients with FHH type 1, 22 patients with FHH type 3, 60 with PHPT, and 24 normal adults.

Intervention: There were no interventions.

Main Outcome Measures: Abnormalities of the CASR, GNA11, and AP2S1 genes, blood calcium, phosphate, and PTH concentrations, urinary calcium excretion were measured.

Results: In 133 families, we detected 101 mutations in the CASR gene, 68 of which were previously unknown, and in 19 families, the three recurrent AP2S1 mutations. No mutation was detected in the GNA11 gene. Patients with FHH type 3 had higher plasma calcium concentrations than patients with FHH type 1, despite having similar PTH concentrations and urinary calcium excretion. Renal tubular calcium reabsorption levels were higher in patients with FHH type 3 than in those with FHH type 1. Plasma calcium concentration was higher whereas PTH concentration and urinary calcium excretion were lower in FHH patients than in PHPT patients. In patients with FHH or PHPT, all data groups partially overlapped.

Conclusion: In our population, AP2S1 mutations affect calcium homeostasis more severely than CASR mutations. Due to overlap, the risk of confusion between FHH and PHPT is high.
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http://dx.doi.org/10.1210/jc.2015-3442DOI Listing
May 2016

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey.

J Clin Immunol 2016 Apr 8;36(3):220-34. Epub 2016 Mar 8.

Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.

Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.

Results: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.

Conclusions: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.
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http://dx.doi.org/10.1007/s10875-016-0252-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792361PMC
April 2016

Cytomegalovirus infection can mimic genetic nephrotic syndrome: a case report.

BMC Nephrol 2015 Sep 22;16:156. Epub 2015 Sep 22.

Pediatric Nephrology Department, Robert Debré Hospital, 48 boulevard Sérurier, 75019, Paris, France.

Background: Nephrotic syndrome is a relatively rare but serious condition in children. Infantile nephrotic syndrome often has a genetic origin; the treatment is then symptomatic, with a poor prognosis, and a rapid evolution to chronic kidney disease. However, non-genetic infantile nephrotic syndrome has been identified. Here we report for the first time in a child a nephrotic syndrome as the sole clinical expression of a cytomegalovirus infection.

Case Presentation: The patient was 5 months old when he presented with a nephrotic syndrome. An exhaustive genetic testing was conducted and came back negative. A viral work-up only showed a positive cytomegalovirus PCR. Antiviral treatment lead to a complete remission of the nephrotic syndrome, with no requirement for steroid therapy. Renal function remained normal throughout follow-up.

Conclusion: Nephrotic syndrome should always be carefully investigated in children. This observation reinforces the connection between viral infections and pediatric nephrotic syndrome, sparking more controversy about an infectious origin to childhood nephrotic disease.
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http://dx.doi.org/10.1186/s12882-015-0152-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580224PMC
September 2015