Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS).
We report a retrospective multicenter series of 52 patients with severe initial ...neurologic involvement that occurred in the course of D+HUS.
Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13.
Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability.
Summary Background We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could ...be explained by patient-level and country-level factors. Methods In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. Findings Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4–16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52–0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 95% CI 1·13–1·53, p=0·0005, to 1·21 0·97–1·51, p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. Interpretation Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities. Funding ERA-EDTA and ESPN.
To describe the quality of life of adolescents initiating haemodialysis, to determine the factors associated with quality of life, and to assess coping strategies and their impact on quality of life.
...All adolescents initiating haemodialysis between September 2013 and July 2015 in French paediatric haemodialysis centres were included. Quality of life data were collected using the "Vécu et Santé Perçue de l'Adolescent et l'Enfant" questionnaire, and coping data were collected using the Kidcope questionnaire. Adolescent's quality of life was compared with age- and sex-matched French control.
Thirty-two adolescents were included. Their mean age was 13.9 ± 2.0 years. The quality of life score was lowest in leisure activities and highest in relationships with medical staff. Compared with the French control, index, energy-vitality, relationships with friends, leisure activities and physical well-being scores were significantly lower in haemodialysis population. In multivariate analyses, active coping was positively associated with quality of life and especially with energy-vitality, relationships with parents and teachers, and school performance. In contrast, avoidant and negative coping were negatively associated with energy-vitality, psychological well-being and body image for avoidant coping, and body image and relationships with medical staff for negative coping.
The quality of life of haemodialysis adolescents, and mainly the dimensions of leisure activities, physical well-being, relationships with friends and energy-vitality, were significantly altered compared to that of the French population. The impact of coping strategies on quality of life seems to be important. Given the importance of quality of life and coping strategies in adolescents with chronic disease, health care professionals should integrate these aspects into care management.
The impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs).
We measured baseline ...systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD.
Normal BP, grade 1, 2 and 3 hypertension were present in 243 (43.1%), 132 (23.4%), 101 (17.9%) and 88 (15.6%), respectively. Significant BP differences were noted in relation to the cause of TMA: highest BP values were found in patients with atypical hemolytic-uremic syndrome (aHUS), pregnancy, transplantation and auto-immune-related TMAs. Normal BP or grade 1 hypertension was found in 17/18 (94.4%) patients with thrombotic thrombocytopenic patients (only 1/18 (5.6%) had a SBP value>150 mmHg). In contrast, BP values could not differentiate isolated "essential" malignant hypertension (MH) from MH associated with aHUS (isolated MH (n=15): BP (median (IQR)): 220 (182-249)/132 (101-150) mmHg; MH with aHUS (n=5): BP: 223 (196-245)/131 (111-144) mmHg). The risk of vigilance disturbances (6.9%, 15.0%, 25.0%, respectively), epileptic seizures (1.5%, 4.0%, 12.5%, respectively) and posterior reversible encephalopathy syndrome (0.76%, 2.97%, 6.82%, respectively) increased with increasing baseline BP values from grade 1 to grade 3 hypertension. ESKD occurred in 35/563 (6.2%) patients (1.23%, 2.27%, 11.9% and 19.3% of patients with normal BP, grade 1, 2 and 3 hypertension, respectively). As compared to patients with normal BP (<120/139 mmHg), grade 1, grade 2 and grade 3 hypertension were associated with a greater risk of ESKD in univariate (OR: 1.91 0.83-4.40, 13.2 3.56-48.9 and 34.8 9.31-130, respectively) and multivariate (OR: 0.89 0.30-2.69, 7.00 1.57-31.3 and 19.7 4.53-85.2, respectively) analyses. The association between BP and the risk of ESRD was unchanged after adjustment on eculizumab use (OR: 3.46 1.41-8.49, 17.7 4.44-70.0 and 70.6 8.61-579, respectively). Patients with MH, regardless of its cause, had a greater risk of ESKD (OR: 26.4 10.0-69.8 vs other patients).
Baseline BP differs in primary and secondary TMAs. High BP reduces the neurological tolerance of TMAs and is a powerful independent risk factor of ESKD, even after adjustment on TMA's cause.
The objective was to develop a population pharmacokinetic‐pharmacogenetic model of mycophenolic acid following administration of mycophenolate mofetil (MMF) in de novo pediatric renal‐transplant ...patients and identify factors that explain variability. The pharmacokinetic samples were collected from 89 de novo pediatric renal‐transplant patients treated with MMF and studied during the first 60 postoperative days. All patients were genotyped for UGT1A8–A9, UGT2B7, and ABCC2. Population pharmacokinetic analysis was performed with the NONMEM and was validated using bootstrap visual predictive check. The pharmacokinetic data were best described by a 2‐compartment model with Erlang distribution to describe the absorption phase. The covariate analysis identified body weight as an individual factor influencing central volume of distribution and concomitant immunosuppressive medication and identified body weight and UGT2B7 802C>T genotype as individual factors influencing apparent oral clearance (CL/F) of MMF. CL/F in cyclosporine‐MMF‐treated patients was 33% higher than in tacrolimus‐MMF‐treated patients. The CL/F was significantly lower in patients with UGT2B7 802 C/C genotype compared with patients with UGT2B7 802 C/T and 802T/T genotypes, and this effect was independent of concomitant immunosuppressive medication or body weight. The population pharmacokinetic‐pharmacogenetic model of mycophenolic acid was validated. Body weight, concomitant medication, and UGT2B7 genotype contribute significantly to the interindividual variability of MMF disposition in pediatric renal‐transplant patients.
Rheumatoid purpura is the most common vasculitis in children, and its renal involvement determines the prognosis. To date, no national protocol exists for its management. A protocol was drafted for ...the French Grand Ouest inter-region in 2011 in order to standardize practices.
The main objective is to evaluate renal sequelae with a median follow-up of 2 years since the implementation of this protocol. The secondary objectives are to evaluate the different therapeutic and diagnostic management.
Inclusion of all children from 2006 to 2018 with nephropathy due to rheumatoid purpura followed in the university hospitals of Rennes, Nantes, Tours, Angers and Brest.
169 patients were included, of whom 104 were treated accroding to protocol and 65 differently. Sequels at 2-year follow-up concerned 27.0% of patients with no significant difference according to whether or not the protocol was followed. A significant decrease of 26.1% in the number of renal biopsies was observed in the group that followed the protocol. The latter was performed with a median delay of less than 30 days.
The protocol allowed a standardization of practices without deleterious consequences at 2 years of follow-up and a decrease in renal biopsy punctures. It is in agreement with the recommendations of KDIGO (Kidney Disease Improving Global Outcomes) and European experts. On the other hand, in view of recent studies and the physiopathology, immunosuppressive drugs other than corticosteroids could be introduced earlier in severe forms.
Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) in children is a severe condition, resulting in approximately 50% of patients requiring RRT. Furthermore, at least 30% of survivors experience ...kidney sequelae. Recently, activation of the complement alternative pathway has been postulated as a factor in STEC-HUS pathophysiology, leading to compassionate use of eculizumab, a monoclonal antibody inhibiting the terminal complement complex, in affected patients. Given the lack of therapy for STEC-HUS, a controlled study of eculizumab efficacy in treating this condition is a priority.
We conducted a Phase 3 randomized trial of eculizumab in children with STEC-HUS. Patients were randomly assigned in a 1:1 ratio to receive either eculizumab or placebo during 4 weeks. Follow-up lasted for 1 year. The primary end point was RRT duration <48 hours after randomization. Secondary endpoints included hematologic and extrarenal involvement.
Baseline characteristics were similar among the 100 patients who underwent randomization. The rate of RRT <48 hours did not differ significantly between the two groups (48% in the placebo versus 38% in the eculizumab group; P = 0.31) or in the course of ARF. The two groups also exhibited similar hematologic evolution and extrarenal manifestations of STEC-HUS. The proportion of patients experiencing renal sequelae at 1 year was lower in the eculizumab group than in the placebo group (43.48% and 64.44%, respectively, P = 0.04). No safety concern was reported.
In pediatric patients with STEC-HUS, eculizumab treatment does not appear to be associated with improved renal outcome during acute phase of the disease but may reduce long-term kidney sequelae.
EUDRACT (2014-001169-28) ClinicalTrials.gov ( NCT02205541 ).
La leptospirose est une anthropozoonose dont le tableau clinique est polymorph e et de gravité variable, allant du syndrome pseudo-grippal à l’insuffisance rénale aiguë menaçante. Cette maladie à ...forte incidence dans les régions tropicales voit son incidence augmenter en France métropolitaine et à la Réunion. L’objectif de cette étude était d’identifier les caractéristiques épidémiologiques, cliniques, biologiques et thérapeutiques des formes pédiatriques de la leptospirose en France métropolitaine et à la Réunion.
Nous avons mené une étude de cohorte des cas de leptospirose pédiatriques hospitalisés dans les centres hospitaliers dans lesquels exercent des membres de la Société de néphrologie pédiatrique (SNP) entre janvier 2008 et décembre 2020. Parmi les centres répondeurs, six avaient eu des cas de leptospirose, un centre en avait eu un en consultation mais dont les données étaient insuffisantes, et dix n’en ont pas retrouvés.
Vingt-et-un cas ont été recensés dans six centres hospitalo-universitaires français (âge moyen 13,4±3,4ans), majoritairement des garçons (ratio 6:1). Parmi les 21 enfants, 95 % avaient de la fièvre, 71 % avaient des myalgies, 81 % avaient une thrombopénie et 76 % ont présenté des symptômes digestifs. Sur le plan rénal, 18 patients (86 %) présentaient une insuffisance rénale, dont 19 % avec oligoanurie, mais aucun n’a nécessité de dialyse. Environ 30 % des patients présentaient des signes biologiques de tubulopathie comprenant une hypophosphatémie, une hypokaliémie ou une protéinurie tubulaire. Il n’y a eu aucun décès. La prise en charge thérapeutique correspondait aux recommandations avec une antibiothérapie par amoxicilline ou céphalosporine de 3e génération associée à un traitement symptomatique de l’atteinte rénale. Lorsqu’il y a eu un contrôle biologique après la sortie, on observait une décroissance de la créatinine.
Dans cette étude rétrospective multicentrique, nous rapportons 21 cas d’infection par leptospirose, avec une proportion importante d’insuffisance rénale, dont l’évolution était favorable. L’évolution vers l’insuffisance rénale chronique ne semble pas être le cas chez les enfants, mais le suivi à distance n’a pas été systématiquement réalisé. Par rapport à des études menées chez les adultes, le pronostic global est meilleur et l’ictère est plus rare. Par rapport à d’autres études pédiatriques, la conjonctivite n’est pas un signe fréquent, mais les atteintes rénales et la survie sont similaires. On pourrait parler de formes rénales anictériques révélatrices. Le recueil de cas n’était pas exhaustif et ne comprenait pas les autres territoires d’outre-mer alors qu’ils regroupent la plus grande proportion d’infection par la leptospirose.
La leptospirose est une infection qui peut être responsable d’une défaillance multiviscérale avec une atteinte rénale conditionnant le pronostic vital. Malgré un meilleur pronostic chez l’enfant, il reste important de diagnostiquer rapidement cette infection afin de mettre en place l’antibiothérapie adaptée et un suivi néphrologique en cas d’atteinte rénale.
Leptospirosis is an anthropozoonosis with polymorphic clinical symptoms and a high variability of severity, ranging from flu-like syndrome to severe acute kidney injury. This disease is highly incident in tropical regions but there is a trend towards increasing incidence in metropolitan France and in Reunion Island. The objective of this study was to describe the epidemiological, clinical, laboratory and therapeutic characteristics of the pediatric leptospirosis in metropolitan France and in Reunion Island.
We performed a retrospective analysis of leptospirosis cases hospitalized in University hospitals where members of the Paediatric Nephrology Society work in France between January 2008 and December 2020, 6 centers reported leptospirosis cases, one center had one patient in consultation but lack of available data and 10 centers did not find any case.
A total of 21 cases were reported (mean age 13.4±3.4years), mostly boys (ratio 6:1). Out of 21 patients, 95% had fever, 71% were presenting with myalgia, 81% with thrombocytopenia, and 76% with gastrointestinal symptoms. Regarding kidney impairment, 18 patients (86%) had acute kidney injury, including 4 (19%) with oligoanuria, but none of them required acute dialysis. About 30% of patients had biological signs of tubulopathy including hypophosphatemia, hypokalemia, or tubular proteinuria. No death due to the disease occurred. The therapeutic management followed the current guidelines with the use of antibiotic therapy by amoxicillin or 3rd generation cephalosporins with symptomatic treatment. When there was biological control after exit, creatinine decreased.
In this multicenter retrospective study, we report 21 children with leptospirosis with a significant proportion of acute kidney injury, the outcome was favorable. Children do not seem to be at high risk of chronic kidney disease progression but nephrology follow-up has not been systematically carried out. Compared to studies performed in adults, the prognosis was better and hepatic impairment was rare. Compared to other pediatric studies, conjunctivitis was not a common symptom but kidney injury and survival appeared to be similar. Children were presenting with anicteric renal presentation. The casebook wasn’t exhaustive and didn’t include the other overseas territories, which account for the highest proportion of leptospirosis infection.
Leptospirosis is an infection which may lead to multivisceral failure with kidney involvement conditioning the outcome. Despite a better prognosis in children, it remains important to quickly diagnose this infection in order to start appropriate antibiotic therapy and perform a kidney function monitoring.
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