Etude à l'âge scolaire des conséquences rénales de la prématurité et du retard de croissance intra-utérin

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Suivi des dilatations pyélo-calicielles de diagnostic anténatal

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Renal involvement in children with HNF1β mutation: Early sonographic appearances and long-term follow-up

Objectives: The aim was to report ultrasound (US) patterns of hepatocyte nuclear factor (HNF1β) mutation throughout childhood and determine whether ultrasound could be predictive of renal failure. Methods: The sonographic examinations in 34 children with HNF1β mutation were reviewed. Their sonographic characteristics were compared with renal function. Results: At first postnatal examination renal length was normal in 44 % of the patients, decreased in 24 %, increased in 12 % and asymmetrical in 20 %. Renal cortex was hyperechoic in 97 %. Corticomedullary differentiation was abnormal in 59 %. Cysts were present in 77 % of patients. Cysts were mostly subcapsular (64 %). Twenty-eight patients had follow-up examinations. A modification of the sonographic appearance was observed in 91 % of patients. Eight patients (23 %) had renal failure; no specific US pattern could be demonstrated. Conclusions: At birth, HNF1β mutation was typically associated on US with the combination of hyperechoic, normal-sized kidneys with abnormal corticomedullary differentiation (CMD) and multiple cortical cysts. In older children, the appearances can be variable: kidneys may have decreased (32 %) or normal size (33 %); they are usually hyperechoic (50 %) with abnormal CMD (78 %) and (sub)cortical cysts (71 %). No pattern appears to be associated with renal failure. Key Points: • HNF1β mutations determine significant anomalies of sonographic appearances of kidneys in children. • Kidneys appear mainly hyperechoic, with or without CMD and with subcapsular cysts. • The US pattern may evolve throughout childhood in the same patient. • No correlation was found between any sonographic pattern and renal failure.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

COPA syndrome as a cause of lupus nephritis

International audienceGenetic kidney diseases are rare situations resulting from mutations in genes expressed in major structures of the kidney, including podocytes, tubular cells, and basement membrane.1 More recently, a new field of monogenic inflammatory diseases has been identified2; these immune-mediated diseases can affect all organs, including the kidney. Here we report on a young girl diagnosed with lupus nephritis and carrying a mutation in the COPA gene encoding for coatomer protein complex subunit alpha

Pediatr Nephrol

BACKGROUND: IgA vasculitis (IgAV) is the most common vasculitis in children. IgAV long-term prognosis depends on kidney involvement or IgA vasculitis with nephritis (IgAVN). To date, steroid treatment (oral steroids or methylprednisolone pulses) has not proven to be formally efficient. This study aimed to assess the role of steroids on IgAVN outcome. METHODS: All children with IgAVN diagnosed 2000-2019 in 14 French pediatric nephrology units with minimal follow-up of 6 months were retrospectively included. Outcomes of patients treated with steroids were compared with those of a control group of untreated patients matched for age, sex, proteinuria, eGFR, and histological features. The primary endpoint was IgAVN remission defined as urine protein-to-creatinine ratio < 20 mg/mmol without impaired eGFR one year after disease onset. RESULTS: A total of 359 patients with IgAVN were included with a median follow-up time of 249 days (range 43-809). One hundred eight (30%) patients received oral steroids alone, 207 (51%) patients received three methylprednisolone pulses followed by oral steroids, and 44 patients (12.5%) did not receive steroids. Thirty-two children treated with oral steroids alone were compared with 32 matched control patients who did not receive steroids. One year after disease onset, IgAVN remission proportion was not different between these two groups: 62% versus 68%, respectively. Ninety-three children treated with oral steroids alone were compared with 93 matched patients treated with three methylprednisolone pulses followed by oral corticosteroids. IgAVN remission proportion was not different between these two groups: 77% versus 73%, respectively. CONCLUSION: The benefit of oral steroids alone and methylprednisolone pulses could not be established based on this observational study. Randomized controlled trials are thus required to determine the efficacy of steroids in IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information

Complement Gene Variants and Shiga Toxin-Producing Escherichia coli-Associated Hemolytic Uremic Syndrome: Retrospective Genetic and Clinical Study

International audienceBACKGROUND AND OBJECTIVES: Inherited complement hyperactivation is critical for the pathogenesis of atypical hemolytic uremic syndrome (HUS) but undetermined in postdiarrheal HUS. Our aim was to investigate complement activation and variants of complement genes, and their association with disease severity in children with Shiga toxin-associated HUS.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Determination of complement biomarkers levels and next-generation sequencing for the six susceptibility genes for atypical HUS were performed in 108 children with a clinical diagnosis of post-diarrheal HUS (75 Shiga toxin-positive, and 33 Shiga toxin-negative) and 80 French controls. As an independent control cohort, we analyzed the genotypes in 503 European individuals from the 1000 Genomes Project.RESULTS: During the acute phase of HUS, plasma levels of C3 and sC5b-9 were increased, and half of patients had decreased membrane cofactor protein expression, which normalized after 2 weeks. Variants with minor allele frequency <1% were identified in 12 Shiga toxin-positive patients with HUS (12 out of 75, 16%), including pathogenic variants in four (four out of 75, 5%), with no significant differences compared with Shiga toxin-negative patients with HUS and controls. Pathogenic variants with minor allele frequency <0.1% were found in three Shiga toxin-positive patients with HUS (three out of 75, 4%) versus only four European controls (four out of 503, 0.8%) (odds ratio, 5.2; 95% confidence interval, 1.1 to 24; P=0.03). The genetic background did not significantly affect dialysis requirement, neurologic manifestations, and sC5b-9 level during the acute phase, and incident CKD during follow-up. However, the only patient who progressed to ESKD within 3 years carried a factor H pathogenic variant.CONCLUSIONS: Rare variants and complement activation biomarkers were not associated with severity of Shiga toxin-associated HUS. Only pathogenic variants with minor allele frequency <0.1% are more frequent in Shiga toxin-positive patients with HUS than in controls

Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome

International audienceOBJECTIVE:17q12 microdeletion syndrome involves 15 genes, including HNF1B, and is considered to confer a high risk of neuropsychiatric disorders. Patients with HNF1B gene deletion diagnosed secondary to renal disorders are only very rarely reported to have neuropsychiatric disorders. Interestingly, however, when tested, patients with HNF1B gene deletion are found to have 17q12 deletion. This brings into question the extent to which 17q12 deletion is genuinely associated with severe neuropsychological disorders and in which patients. In this study, we sought to confirm 17q12 microdeletion in kidney patients initially diagnosed with HNF1B gene deletion and evaluate neuropsychological disorders in these patients compared with those with HNF1B point mutation.PATIENTS AND DESIGN:Thirty-nine children with HNF1B disorders (26 with deletions) diagnosed secondary to renal abnormalities were included in this prospective study and tested for 17q12 microdeletion and neuropsychological disorders.RESULTS:The same 17q12 microdeletion found in patients with neuropsychological disorders was identified in all of our patients with HNF1B deletion. Neurological examinations found no severe impairments except for one patient with autism. No significant differences were found between patients with deletions and those with point mutations as concerns learning abilities and schooling. Nevertheless, patients with deletions tended to have lower developmental quotients and more difficulties at school.CONCLUSIONS:Complete deletion of the HNF1B gene and 17q12 microdeletion syndrome are actually the same genetic disorder. The neuropsychological phenotype of patients appears less severe when 17q12 deletion is diagnosed secondary to kidney rather than neuropsychological abnormalities. These data may influence antenatal counselling

Transplantation

Kidney transplantation (KT) is the optimal treatment for children with end-stage kidney disease. The aim of this study was to evaluate the impact of preemptive kidney transplantation (PKT) and of pretransplant dialysis duration on graft survival among French pediatric kidney transplant recipients. We analyzed all first pediatric kidney-only transplantations performed in France between 1993 and 2012. A Cox multivariable model was used to investigate the association of PKT and pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis, or retransplant, whichever occurred first. Patients (n = 1911) were included, of which 380 (19.8%) received a PKT. Median time of follow-up was 7.0 y. PKT was associated with a 55% reduction of the hazard of graft failure at any time after KT compared with patients transplanted after dialysis (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62), after adjustment for recipient sex and age, primary kidney disease, donor age and type (living or deceased donor), number of HLA mismatches, cold ischemia time, and year of transplantation. A reduction of the hazard of graft failure was found in PKT whatever the compared duration of dialysis, even when <6 mo and whatever the dialysis modality. Results were similar in multiple sensitivity analyses. In France, PKT among pediatric patients is associated with a better graft survival when compared with KT after dialysis, even when <6 mo. Based on these findings, we suggest that PKT should be considered as the treatment of choice for children with end-stage kidney disease

Renal replacement therapy in adult and pediatric intensive care : Recommendations by an expert panel from the French Intensive Care Society (SRLF) with the French Society of Anesthesia Intensive Care (SFAR) French Group for Pediatric Intensive Care Emergencies (GFRUP) the French Dialysis Society (SFD).

Acute renal failure (ARF) in critically ill patients is currently very frequent and requires renal replacement therapy (RRT) in many patients. During the last 15&nbsp;years, several studies have considered important issues regarding the use of RRT in ARF, like the time to initiate the therapy, the dialysis dose, the types of catheter, the choice of technique, and anticoagulation. However, despite an abundant literature, conflicting results do not provide evidence on RRT implementation. We present herein recommendations for the use of RRT in adult and pediatric intensive care developed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system by an expert group of French Intensive Care Society (SRLF), with the participation of the French Society of Anesthesia and Intensive Care (SFAR), the French Group for Pediatric Intensive Care and Emergencies (GFRUP), and the French Dialysis Society (SFD). The recommendations cover 4 fields: criteria for RRT initiation, technical aspects (access routes, membranes, anticoagulation, reverse osmosis water), practical aspects (choice of the method, peritoneal dialysis, dialysis dose, adjustments), and safety (procedures and training, dialysis catheter management, extracorporeal circuit set-up). These recommendations have been designed on a practical point of view to provide guidance for intensivists in their daily practice

Transplantation

Kidney transplantation (KT) is the optimal treatment for children with end-stage kidney disease. The aim of this study was to evaluate the impact of preemptive kidney transplantation (PKT) and of pretransplant dialysis duration on graft survival among French pediatric kidney transplant recipients. We analyzed all first pediatric kidney-only transplantations performed in France between 1993 and 2012. A Cox multivariable model was used to investigate the association of PKT and pretransplant dialysis time with the hazard of graft failure defined as death, return to dialysis, or retransplant, whichever occurred first. Patients (n = 1911) were included, of which 380 (19.8%) received a PKT. Median time of follow-up was 7.0 y. PKT was associated with a 55% reduction of the hazard of graft failure at any time after KT compared with patients transplanted after dialysis (hazard ratio, 0.45; 95% confidence interval, 0.33-0.62), after adjustment for recipient sex and age, primary kidney disease, donor age and type (living or deceased donor), number of HLA mismatches, cold ischemia time, and year of transplantation. A reduction of the hazard of graft failure was found in PKT whatever the compared duration of dialysis, even when <6 mo and whatever the dialysis modality. Results were similar in multiple sensitivity analyses. In France, PKT among pediatric patients is associated with a better graft survival when compared with KT after dialysis, even when <6 mo. Based on these findings, we suggest that PKT should be considered as the treatment of choice for children with end-stage kidney disease