Publications by authors named "Saoussen Krid"

24 Publications

  • Page 1 of 1

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

Pediatr Nephrol 2021 Feb 24. Epub 2021 Feb 24.

University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.

Background: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF).

Methods: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile.

Results: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003).

Conclusions: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.
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http://dx.doi.org/10.1007/s00467-021-04930-2DOI Listing
February 2021

Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.

Pediatr Nephrol 2020 Nov 9. Epub 2020 Nov 9.

Department of Gastroenterology-Hepatology-Nutrition, Reference Center for Biliary Atresia and Cholestatic Genetic Diseases, Hôpital Universitaire Necker-Enfants Malades, AP-HP, Paris, France.

Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood.

Methods: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study.

Results: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt.

Conclusions: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant.
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http://dx.doi.org/10.1007/s00467-020-04808-9DOI Listing
November 2020

Association between 25(OH) vitamin D and graft survival in renal transplanted children.

Pediatr Transplant 2020 11 26;24(7):e13809. Epub 2020 Aug 26.

Service de Néphrologie Pédiatrique, Centre de référence MARHEA, Hôpital Necker-Enfants malades, Paris, France.

Background: In children, vitamin D deficiency is common after renal transplantation. Besides promoting bone and muscle development, vitamin D has immunomodulatory effects, which could protect kidney allografts. The purpose of this study was to assess the association between vitamin D status and the occurrence of renal rejection.

Methods: We studied a retrospective cohort of 123 children, who were transplanted at a single institution between September 2008 and April 2019. Patients did not receive vitamin D supplementation systematically. In addition, factors influencing vitamin D status were analyzed using univariate and multivariate analyses.

Results: Median 25-hydroxy-vitamin D (25-OH-D) concentration was close to reference values at the time of transplantation (30 ng/mL (min-max 5-100)), but rapidly decreased within the first 3 months to 19 ng/mL (min-max 3-91) (P < .001). The overall acute rejection rate was 7%. The clinical rejection rate (5% vs 9%), subclinical rejection (12% vs 36%), and borderline changes (21% vs 28%) were not statistically different during the follow-up between the 3-month 25-OH-D < 20 ng/mL and 3-month 25-OH-D > 20 ng/mL groups. There was a correlation between the 25-OH-D levels and PTH concentration at 3 months (r = -.2491, P = .01), but no correlation between the 3-month 25-OH-D and the season of the year (F = 0.19, P = .90; F = 1.34, P = .27, respectively). Multivariate analyses revealed that age and mGFR at 3 months, were independent predictors of mGFR at 12 months.

Conclusion: Our data show that vitamin D deficiency can develop rapidly after transplantation; vitamin D levels at 3 months are not associated with lower mGFR or a higher rejection rate at 1 year in children as opposed to adult recipients.
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http://dx.doi.org/10.1111/petr.13809DOI Listing
November 2020

Donor-targeted serotherapy as a rescue therapy for steroid-resistant acute GVHD after HLA-mismatched kidney transplantation.

Am J Transplant 2020 08 10;20(8):2243-2253. Epub 2020 Mar 10.

Paris University, Paris, France.

Acute graft-versus-host disease (GVHD) is a rare but frequently lethal complication after solid organ transplantation. GVHD occurs in unduly immunocompromised hosts but requires the escalation of immunosuppression, which does not discriminate between host and donor cells. In contrast, donor-targeted therapy would ideally mitigate graft-versus-host reactivity while sparing recipient immune functions. We report two children with end-stage renal disease and severe primary immune deficiency (Schimke syndrome) who developed severe steroid-resistant acute GVHD along with full and sustained donor T cell chimerism after isolated kidney transplantation. Facing a therapeutic dead end, we used a novel strategy based on the adoptive transfer of anti-HLA donor-specific antibodies (DSAs) through the transfusion of highly selected plasma. After approval by the appropriate regulatory authority, an urgent nationwide search was launched among more than 3800 registered blood donors with known anti-HLA sensitization. Adoptively transferred DSAs bound to and selectively depleted circulating donor T cells. The administration of DSA-rich plasma was well tolerated and notably did not induce antibody-mediated rejection of the renal allografts. Acute GVHD symptoms promptly resolved in one child. This report provides a proof of concept for a highly targeted novel therapeutic approach for solid organ transplantation-associated GVHD.
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http://dx.doi.org/10.1111/ajt.15827DOI Listing
August 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

Long-term outcome of methylmalonic aciduria after kidney, liver, or combined liver-kidney transplantation: The French experience.

J Inherit Metab Dis 2020 03 11;43(2):234-243. Epub 2020 Feb 11.

Reference Center of Inherited Metabolic Diseases, Hôpital Universitaire Necker-Enfants Malades, APHP, Imagine Institute, Filière G2M, MetabERN, INEM, University Paris Descartes, Paris, France.

Organ transplantation is discussed in methylmalonic aciduria (MMA) for renal failure, and poor quality of life and neurological outcome. We retrospectively evaluated 23 French MMA patients after kidney (KT), liver-kidney (LKT), and liver transplantation (LT). Two patients died, one after LKT, one of hepatoblastoma after KT. One graft was lost early after KT. Of 18 evaluable patients, 12 previously on dialysis, 8 underwent KT (mean 12.5 years), 8 LKT (mean 7 years), and 2 LT (7 and 2.5 years). At a median follow-up of 7.3 (KT), 2.3 (LKT), and 1.0 years (LT), no metabolic decompensation occurred except in 1 KT. Plasma and urine MMA levels dramatically decreased, more after LKT. Protein intake was increased more significantly after LKT than KT. Enteral nutrition was stopped in 7/8 LKT, 1/8 KT. Early complications were frequent after LKT. Neurological disorders occurred in four LKT, reversible in one. Five years after KT, four patients had renal failure. The metabolic outcomes were much better after LKT than KT. LKT in MMA is difficult but improves the quality of life. KT will be rarely indicated. We need more long-term data to indicate early LT, in the hope to delay renal failure and prevent neurodevelopmental complications.
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http://dx.doi.org/10.1002/jimd.12174DOI Listing
March 2020

Continuous ambulatory peritoneal dialysis (CAPD) in children: a successful case for a bright future in a developing country.

Pan Afr Med J 2019 30;33:71. Epub 2019 May 30.

Pediatric Unit, Albert Royer's Children Centre, Dakar, Sénégal.

The authors report the first case of successful peritoneal dialysis (PD) in a developing country performed about a 13-year-old adolescent followed-up for stage V chronic kidney disease (CKD) with anuria. After 3 months of hemodialysis, the parents opted for continuous ambulatory peritoneal dialysis (CAPD) as they wished to return home located 121km from Dakar. After PD catheter insertion, the plan proposed to the patient consisted 3-4 hours stasis of isotonic dialysate during the day and a night stasis of 8 hours of icodextrin for an injection volume of 1L per session. The patient and his mother were trained and assessed on the PD technique. After dialysis adequacy was tested while hospitalised, they were able to return home and continued the sessions following the same plan prescribed and while keeping in touch, by telephone, with the medical team. The technique assessment at the day hospital every 2 weeks revealed dialysis adequacy and satisfactory tolerance of PD at home after 04 months of observation. It was the first case of successful CAPD in the pediatrics unit in this context. Scaling this technique is a challenge for the pediatric nephrologist in developing countries like Senegal.
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http://dx.doi.org/10.11604/pamj.2019.33.71.17042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689834PMC
September 2019

Haemodiafiltration does not lower protein-bound uraemic toxin levels compared with haemodialysis in a paediatric population.

Nephrol Dial Transplant 2020 04;35(4):648-656

Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium.

Background: Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment.

Methods: In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5-20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months.

Results: For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01).

Conclusions: While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research.
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http://dx.doi.org/10.1093/ndt/gfz132DOI Listing
April 2020

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population.

Toxins (Basel) 2019 04 24;11(4). Epub 2019 Apr 24.

Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort ( = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4-5 ( = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4-5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF ( -0.2 to -0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4-5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.
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http://dx.doi.org/10.3390/toxins11040235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521157PMC
April 2019

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

J Am Soc Nephrol 2019 04 7;30(4):678-691. Epub 2019 Mar 7.

Nephrology Unit, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce.

Methods: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score.

Results: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher 2-microglobulin. The HDF cohort had lower 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time.

Conclusions: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.
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http://dx.doi.org/10.1681/ASN.2018100990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442347PMC
April 2019

Influenza vaccination among children with idiopathic nephrotic syndrome: an investigation of practices.

BMC Nephrol 2019 02 25;20(1):65. Epub 2019 Feb 25.

Néphrologie Pédiatrique, Centre de Référence du Syndrome Néphrotique Idiopathique de l'enfant et l'adulte, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne paris Cité, 149 rue de Sèvres, 75015, Paris, France.

Background: Annual influenza vaccination is recommended for all children with idiopathic nephrotic syndrome (INS) in France. Consequently, the Social Security automatically sends prescriptions to all patients suffering from a chronic disease. The aim of this study was to evaluate the follow-up to these recommendations.

Methods: We conducted a monocentric retrospective investigation of practices. We included all children with steroid-sensitive INS in remission who attended our clinics from January 1st 2015 to January 1st 2017, resided in France and had a valid phone number. Data were collected from May 2017 to June 2017 through a phone interview and review of clinical charts.

Results: 75 patients met the inclusion criteria. The parents of 57 children could be reached by phone and agreed to participate to the survey. 35/57 (61.4%) declared having received a prescription during the 2016-2017 campaign. Only 14 children (24.6%) were vaccinated. 17/43 (39.5%) parents of unvaccinated children had concerns about the safety of the vaccine, 16/43 (37.2%) were not aware of the recommendations, 5/43 (11.6%) had been recommended by their physician not to vaccinate their child, 3/43 (7%) forgot to have them vaccinated and 2/43 (4.6%) reported no reason. 13/43 (30%) unvaccinated children presented a relapse during the flu season - 2/13 during an influenza-like illness - whereas 1/14 (7%) immunized children presented a relapse during the six months of post-vaccination follow-up. Relapse rates were not increased in vaccinated children compared to unvaccinated children (p = 0.15), nor in the 6 months following vaccination compared to the 6 months prior (1/14 vs 5/14, p = 0.20).

Conclusions: 1) < 2/3 patients were properly prescribed the recommended yearly influenza vaccination at our center 2) only 1/4 were vaccinated and most of their parents were misinformed. Physicians must be aware of this and should make every effort to better inform their patients on the risks of flu illness and the benefits and safety of the vaccination.
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http://dx.doi.org/10.1186/s12882-019-1240-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388483PMC
February 2019

Pharmacokinetics of Enoxaparin After Renal Transplantation in Pediatric Patients.

J Clin Pharmacol 2018 12 26;58(12):1597-1603. Epub 2018 Sep 26.

Néphrologie pédiatrique, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Institut Imagine, Université Paris Descartes, Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.

Enoxaparin is commonly used in the prevention of renal allograft vascular thrombosis but off-label in children, and no consensus exists regarding the optimal dosing and dose adjustment. In this retrospective study, 444 anti-Xa levels were obtained from 30 pediatric renal transplant recipients in order to investigate enoxaparin population pharmacokinetics. The main results were (1) 25% of children achieved the target anti-Xa activity 36 hours after initiation of treatment, (2) anti-Xa time courses were best described by a 1-compartment open model with first-order absorption, (3) body weight but not renal function was the sole covariate influencing clearance and volume of distribution, and (4) large between-subject and between-occasion variabilities in anti-Xa activity were observed. However, creatinine-based estimated glomerular filtration rate in the first post-renal transplantation hours may not reliably reflect the actual renal function of the children. Based on the final population model, a Bayesian-based program was developed in order to estimate the individual pharmacokinetic parameters on a single anti-Xa measurement, allowing determination of the next enoxaparin dose that will quickly achieve an appropriate anti-Xa activity (targeting 0.3-0.5 IU/mL) and anticoagulation. Finally, these results should help standardize practices that remain to date largely heterogeneous in pediatric intensive care units.
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http://dx.doi.org/10.1002/jcph.1289DOI Listing
December 2018

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BMC Nephrol 2018 08 10;19(1):199. Epub 2018 Aug 10.

Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population.

Methods: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38).

Discussion: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD.

Trial Registration: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.
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http://dx.doi.org/10.1186/s12882-018-0998-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086045PMC
August 2018

Pulmonary hypertension in an adolescent with end-stage-renal disease-a diagnostic challenge: Answers.

Pediatr Nephrol 2019 01 12;34(1):73-74. Epub 2018 Mar 12.

Pediatric Cardiology Department, Necker University Hospital, APHP, Paris, France.

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http://dx.doi.org/10.1007/s00467-018-3939-xDOI Listing
January 2019

Pulmonary hypertension in an adolescent with end-stage-renal disease-a diagnostic challenge: Questions.

Pediatr Nephrol 2019 01 12;34(1):71. Epub 2018 Mar 12.

Pediatric Cardiology Department, Necker University Hospital, APHP, Paris, France.

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http://dx.doi.org/10.1007/s00467-018-3931-5DOI Listing
January 2019

Immunoadsorption in Anti-GBM Glomerulonephritis: Case Report in a Child and Literature Review.

Pediatrics 2017 Nov;140(5)

Department of Pediatric Nephrology, MARHEA - Necker Hospital - APHP, Imagine Institute, Paris Descartes University, Paris, France; and

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare autoimmune disease that is characterized by rapidly progressive glomerulonephritis that may be associated with pulmonary hemorrhage. Anti-GBM GN is caused by autoantibodies (classically type G immunoglobulin) directed against the α3 subunit of type IV collagen. Without any appropriate treatment, the disease is generally fulminant, and patient and kidney survival is poor. The current guidelines recommend the use of plasma exchanges and immunosuppressive drugs. Immunoadsorption (IA) can remove pathogenic IgGs from the circulation and do not require plasma infusions, contrary to plasma exchanges. IA has seldom been used in adult patients with good tolerance and efficiency. We report herein the first pediatric case successfully treated with IA combined with immunosuppressive drugs in a 7-year-old girl who presented acute kidney injury (estimated glomerular filtration rate 38 mL/minute/1.73 m). A kidney biopsy revealed numerous >80% glomerular crescents and linear IgG deposits along the glomerular basement membrane. Ten IA sessions led to rapid and sustained clearance of autoantibodies and improvement of kidney function until 21 months after onset (glomerular filtration rate 87 mL/minute/1.73 m). No adverse effect was noted. This report adds to the growing body of evidence suggesting IA as a therapeutic alternative to plasma exchanges in anti-GBM GN. The other 27 published pediatric cases of anti-GBM GN are reviewed.
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http://dx.doi.org/10.1542/peds.2016-1733DOI Listing
November 2017

Treatment by immunoadsorption for recurrent focal segmental glomerulosclerosis after paediatric kidney transplantation: a multicentre French cohort.

Nephrol Dial Transplant 2018 06;33(6):954-963

CHU Nantes, Hôpital Mère-Enfants, Néphrologie et Hémodialyse Pédiatrique, Nantes, France.

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation (KTx) in children. This can lead to delayed graft loss. As the management of children with recurrent FSGS is not well established, apheresis strategies could be a cornerstone to control the disease. Immunoadsorption (IA) is a recent apheresis therapy. There have been few studies examining IA in this setting. We report the results of IA for management of recurrent FSGS after KTx in children in France.

Methods: We included all children treated with IA for early FSGS recurrence after KTx between January 2011 and June 2014 in France. We excluded genetic forms of FSGS. Patients' characteristics and technical data on IA were retrospectively collected. Recurrence was defined as nephrotic proteinuria during the post-transplantation period. Partial and complete remissions were defined when urine protein:creatinine ratios were less than 0.2 and 0.05 g/mmol, respectively.

Results: Twelve patients, from six paediatric KTx units, presenting with FSGS recurrence between 0 and 21 days after KTx were treated with IA. Ten of 12 children were responders: 2 achieved partial remission and 8 complete remission. The decrease of proteinuria rapidly occurred within the first 10 sessions after initiating IA. After 3 months of IA, two patients maintained remission without IA and eight became IA dependent. No severe side effects were reported.

Conclusions: Our study reports on the efficacy of IA in the recurrence of FSGS after KTx in children. Further prospective controlled studies are required to confirm these results and to optimize the management of FSGS recurrence after paediatric KTx.
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http://dx.doi.org/10.1093/ndt/gfx214DOI Listing
June 2018

Presentations and outcomes of juvenile dermatomyositis patients admitted to intensive care units.

Rheumatology (Oxford) 2017 Oct;56(10):1814-1816

Service d'Immunologie, Hématologie et Rhumatologie Pédiatrique, Centre de Référence National des Maladies Rhumatologiques et Inflammatoires Pédiatriques (CERHUMIP), Hôpital Necker - Enfants Malades, AP-HP Paris.

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http://dx.doi.org/10.1093/rheumatology/kex267DOI Listing
October 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

Body composition monitoring-derived urea distribution volume in children on chronic hemodialysis.

Pediatr Nephrol 2016 Jun 11;31(6):991-9. Epub 2016 Jan 11.

Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.

Background: Modern hemodialysis (HD) machines are able to measure ionic dialysance online and thereby continuously monitor Kt/V. The accuracy of measurement depends on the input of the correct urea distribution volume (V), available from anthropometric equations and body composition monitoring (BCM). The latter method, however, has not been validated in children.

Methods: We compared V determined by BCM to that calculated using four different anthropometric formulas (Morgenstern, Mellits and Cheek, Hume-Weyers and Watson equations) in 23 pediatric HD patients. We also compared online Kt/V using BCM-derived V with the Kt/V calculated from pre- and post-dialytic urea concentrations using the single-pool second-generation Daugirdas equation.

Results: The V calculated by the Morgenstern equation was similar to that derived by BCM, with a mean difference of -0.7% (95% limits of agreement -11.7 to 10.3%). In contrast, the V calculated by the other equations was 5.4, 6.2 and 18%, respectively higher than the BCM-derived V. The mean difference between Kt/V calculated using the Daugirdas equation and online Kt/V determination based on BCM-derived V data was 0.10 (95% limits of agreement -0.50 to 0.70%).

Conclusions: In our pediatric HD patients the V measured by BCM was in agreement with that calculated using the Morgenstern equation, which is the only equation which has been validated to date in children on dialysis. Online determination of Kt/V using a BCM-derived V largely agreed with that calculated by the Daugirdas equation. We therefore conclude that the former approach is suitable for frequent online assessment of dialytic small solute clearance.
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http://dx.doi.org/10.1007/s00467-015-3283-3DOI Listing
June 2016

Hydration measurement by bioimpedance spectroscopy and blood pressure management in children on hemodialysis.

Pediatr Nephrol 2013 Nov 7;28(11):2169-77. Epub 2013 Jul 7.

Nephrology Dialysis Transplantation Children's Unit, University Hospital Hautepierre, 1, Avenue Molière, 67098, Strasbourg, France.

Background: Hypertension is frequent in chronic hemodialyzed patients and usually treated by reducing extracellular fluid. Probing dry weight only based on a clinical evaluation may be hazardous, especially in case of volume independent hypertension.

Methods: We performed a 1-year retrospective study in three pediatric centers to define the relation between blood pressure (BP) and hydration status, assessed by whole-body bioimpedance spectroscopy (BIS). We analyzed 463 concomitant measurements of BP, relative overhydration (rel.OH), and plasma sodium (Napl) in 23 children (mean age 13.9 ± 5.1 years).

Results: Pre-dialytic under-hydration (rel.OH < -7%) was present in 5.4% of the sessions, out of which 24% showed hypertension. Normohydration (rel.OH -7 - +7%) was observed in 62.4% of the sessions, 45.3% of them revealed hypertension. Moderate OH (rel.OH +7 - +15%) was present in 21% of the sessions, 47.4% of them showed normal BP. In 11.2% of the sessions, severe overhydration (rel.OH > +15%) was assessed, however, the majority (73%) showed normal BP. Patient-specific Napl setpoint could not be described. Mean dialysate sodium concentration was higher than mean Napl.

Conclusions: Hypertension is not always related to overhydration. Therefore, BIS should restrict the practice of "probing dry weight" in hypertensive children. Moreover, sodium dialytic balance needs to be considered to improve BP management.
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http://dx.doi.org/10.1007/s00467-013-2540-6DOI Listing
November 2013

[Idiopathic steroid-resistant nephrotic syndrome in child : study of 20 cases].

Tunis Med 2011 Jun;89(6):522-8

Service de pediatrie, CHU Sashloul, Sousse, Tunisie.

Background: Idiopathic steroid-resistant nephrotic syndrome (ISRNS) is rare and represents a significant therapeutic dilemma for paediatricians and paediatric nephrologists.

Aim: To analyze characteristics of the ISRNS in the child.

Methods: Retrospective study of 20 cases of ISRNS enrolled in paediatric department of nephrology in Sahloul hospital (Tunisia) between June 1993 and December 2007 (14 years period).

Results: There were eight girls and 12 boys (mean age: 5.8± 3.7 years) originating from the center or the south of Tunisia. Eight of them had a minimal-change disease (MCD), 11 a focal and segmental glomerulosclerosis (FSGS) and one a mesangioproliferative glomerulonephritis (MePGN). In this group, no family form could be identified. All patients were treated by cyclosporine associated with low dose of steroid. We noted a complete remission (CR) in nine cases, partial remission (PR) in three cases and no response to cyclosporine in eight cases. Among patients with CR, six presented MCD and three a FSGS. In this group, we observed relapse of nephrotic syndrome in six cases. End stage renal disease (ESRD) was noted in 10 patients of which five not responded to cyclosporine, two initially having presented a RC and three having since the beginning a PR. Among them, two only could be grafted; one relapses on transplant was observed with a single patient initially presenting a secondarily transformed MePGN in FSGS.

Conclusion: Our study confirms the clinical, histological and evolutive heterogeneity of idiopathic steroid-resistant nephrotic syndrome. Although there is any therapeutic consensus in this domain, cyclosporine remains indicated in first intention in sporadic forms of ISRNS. On the other hand, renal transplantation constitutes the only therapeutic alternate in genetic forms that constantly evolve at ESRD.
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June 2011

[Uremic and haemolytic syndrome in children: study of 17 cases].

Tunis Med 2008 May;86(5):479-85

Service de pédiatrie du CHU Sahloul, Sousse, Tunisie.

Background: In spite of its rarity, the haemolytic and uremic syndrome (HUS) constitutes the first aetiology of acute renal insufficiency (ARI) in child.

Aim: The aim of this work is to analyze clinical and evolutive aspects of the HUS in child.

Method: We studied retrospectively 17 cases of HUS in child enrolled in the paediatrics' department of Sahloul Hospital during eight years period (1996 to 2003).

Results: It is about four boys and 13 girls (sex-ratio = 0.3) aged three months to nine years (mean age: 32 months). Typical HUS was observed in eight child and atypical HUS in the nine others which three presenting a familial form and one associated with steroid resistant nephrotic syndrome. Diagnosis of HUS was established on the classic triad of the disease (anaemia, thrombopenia and ARI) and/or by the histology. Extra-renal manifestations (neurological or digestive involvement) were observed in 11 patients. A blood transfusion was indicated in 13 patients presenting severe anaemia. Peritoneal dialysis was indicated for nine patients while three others required haemodialysis because renal insufficiency had evolved quickly to the end stage. Thirteen cases of HUS (eight typical and five atypical) have received plasma therapy during two to five days. The short-term evolution was favourable with recuperation of normal renal function in seven cases (five with typical SHU and two with atypical SHU). Three children developed terminal renal insufficiency and were currently in haemodialysis. Five patients (four cases of atypical HUS and one case of typical HUS) died of the continuations of the ARI and/or nosocomial infection.

Conclusion: The HUS remains a serious illness because of the risk of complications that can occur to short and long-term. Currently, the specific treatment is only recommended in patients presenting an atypical form of HUS.
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May 2008

[Lupus nephritis in childhood: clinical and evolutive study of 14 cases].

Tunis Med 2007 Aug;85(8):644-50

Service de pédiatrie du CHU Sahloul, Sousse, Tunisie.

Background: Renal involvement is one of the most severe and frequent manifestations of the systemic lupus erythematosus (SLE). Aim : In this study, we analyzed clinical and evolutive particularities of 14 paediatric cases of lupus nephritis (LN).

Methods: It's a retrospective study in 14 children with lupus nephritis followed-up in the paediatrics department of Sousse and Mahdia between 1983 and 2004.

Results: There were 12 girls and two boys (sex-ratio = 0.16) aged four to 14 years (mean age =10 years). At the first presentation, we noted proteinuria in all patients with nephrotic syndrome in six cases, hypertension with variable severity in five cases, hematuria in six cases and a variable severity of renal insufficiency in six cases. Histological examination of kidney performed in 10 patients with severe nephropathy, revealed class IV glomerulonephritis in four cases, class V in two cases and class III in four cases. Thirteen patients were treated by corticosteroids associated with immunosuppressive agent in six cases. One patient had not received any treatment. Five patients were died of the continuations of SLE complications or immunosuppressive therapy. For the other patients, one is in clinical and biological remission since six years, four are lost of view, one is in end stage renal failure, two presented relapsing evolution and one presents refractory form of LN.

Conclusion: Lupus nephritis is severe in our patients with predominance of class III and IV. New therapeutic strategies permitted to improve the renal survival but at the cost of an important iatrogenic morbidity.
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August 2007