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Resume Position du probleme En France, les maladies chroniques touchent 3 millions d’enfants et d’adolescents. Le devenir a long terme des enfants malades chroniques est souvent bien decrit au niveau somatique, mais mal connu dans ses aspects sociaux et psychologiques. Methodes Notre objectif etait de construire un auto-questionnaire d’evaluation du bien-etre d’adultes porteurs de maladie chronique dans ou depuis l’enfance, et non specifique d’une pathologie donnee. Le questionnaire a ete elabore en equipe pluridisciplinaire (epidemiologistes, cliniciens, sociologue, statisticien). Les items ont ete construits en adequation avec des donnees de reference en population generale francaise (issues d’enquetes nationales et en acces libre) pour permettre des analyses comparatives avec ajustement sur âge et sexe (et eventuellement d’autres facteurs confondants comme le niveau d’etudes) par standardisation indirecte (variables qualitatives) ou par Z-scores (variables quantitatives). Une premiere version du questionnaire a ete testee dans quatre etudes menees aupres d’adultes malades chroniques depuis l’enfance. Resultats Le GEDEPAC-2 comporte 108 items explorant 11 domaines du bien-etre : education, emploi, logement, securite materielle, liens sociaux, engagement civique, loisirs, environnement, sante physique/conduites a risque, qualite de vie liee a la sante, vie sexuelle. La vie sociale est abordee conjointement par des questions factuelles (donnees objectives) et des echelles de satisfaction (donnees subjectives). La qualite de vie est analysee en termes de qualite de vie physique, qualite de vie psychique, de fatigue et de poids du traitement de la maladie par trois questionnaires courts valides en francais (SF-12 ; MFI-20 ; « Treatment Burden Questionnaire »). Deroulement et vecu de la transition pediatrie-medecine d’adultes sont decrits a travers 21 items. Des versions papier et electronique ont ete construites. Conclusion Construit dans une approche multidimensionnelle du bien-etre et en adequation avec les donnees de reference disponibles, le questionnaire GEDEPAC-2 facilitera la mise en place de futures etudes sur le devenir a l’âge adulte des enfants malades chroniques.

Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation. A major advance consisted of the identification of the alternative complement pathway in the pathogenesis of aHUS, thus paving the way for the use of the C5a inhibitor eculizumab in this indication. Eculizumab has thereafter dramatically improved the management of patients affected with aHUS. During spring 2011, a great epidemic of entero-hemorrhagic Escherichia coli (EHEC) associated HUS occurred in Germany, providing clinicians the opportunity to examine the relevance of antibiotic prophylaxis, plasma exchange and eculizumab in EHEC-associated HUS. In this work, we herein present advances achieved in the setting of therapeutic management and prognosis in HUS and other related TMA syndromes.

Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature. HUS can result from toxins stemming from bacterial infections of the digestive tract, alternate complement pathway abnormalities, metabolic or coagulation disorders or, lastly, drug and various toxic compounds. The diverse forms of HUS reflect the insights gained in the understanding of the pathophysiological mechanisms underpinning TMA. In this first part, a broad overview of the epidemiological, physiopathological and clinical aspects of HUS and related TMA syndromes is presented.

In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being.Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach. The questionnaire was constructed by a multidisciplinary group (epidemiologists, clinicians, sociologist, statistician). Items were built in compliance with reference data from the French general population (national surveys, free access) to allow comparative analysis adjusted for age and sex (and eventually other confounding factors) by indirect standardization (qualitative variables) or Z-scores (quantitative variables).The GEDEPAC-2 includes 108 items exploring 11 domains: education, employment, housing, material security, social links, civic engagement, leisure, environment, physical health/risky behavior, health-related quality of life and sex life. Factual questions and satisfaction scales jointly explore social well-being. Quality of life is analyzed in terms of physical quality of life, mental quality of life, fatigue and burden of treatment by 3 questionnaires validated in French (SF-12; MFI-20; Burden of Treatment Questionnaire). Experience of transition from pediatric to adult healthcare is described in 21 items. Paper and electronic versions were developed.Built in a multidimensional approach to well-being and in line with the available reference data, GEDEPAC-2 will facilitate the implementation of future studies on impact in adulthood of chronic disease in childhood.

El tratamiento de la hipertension arterial en el nino y el adolescente tiene dos destinatarios: la poblacion de ninos con hipertension arterial esencial, la cual por lo general es moderada y esta asociada a obesidad, y la de los ninos con hipertension arterial secundaria, generalmente grave y originada por una enfermedad renal o vasculorrenal. El control del exceso ponderal del nino hipertenso es un problema de salud publica que necesita un cambio en la alimentacion y el estilo de vida, con aumento de la actividad fisica. Durante la ultima decada se han realizado varios estudios aleatorizados, controlados con placebo, sobre la relacion dosis-efecto, la tolerancia y la farmacocinetica de diversos antihipertensores en el nino. Los inhibidores de la enzima convertidora y, mas recientemente, los antagonistas de los receptores de la angiotensina II, han supuesto aportaciones considerables por su eficacia sobre la presion arterial y tambien sobre la proteinuria y la evolucion de la insuficiencia renal en la nefropatia cronica. En las hipertensiones arteriales mas acentuadas puede ser necesario asociar un inhibidor de la enzima convertidora (o un antagonista de los receptores de la angiotensina II), un antagonista del calcio, un betabloqueante y un diuretico. Aun hay que desarrollar formas galenicas adecuadas para los ninos y estudiar si la eficacia de los antihipertensores sobre la presion arterial y la hipertrofia ventricular izquierda se asocia a la prevencion de las lesiones de aterosclerosis, principal factor de morbilidad y mortalidad cardiovascular en adultos.

14 children with proven or presumably immunologically mediated tubulo-interstitial nephritis are presented. In 2 patients anti-tubular basement membrane antibodies were detected. In 6 immunofluorescence microscopy showed granular deposits of immunoglobulin and/or complement likely representing interstitial location of immune complexes. The findings by immunofluorescence were not significant in the remaining 6 patients. However, the association of renal disease to extra-renal disorders, namely chronic active hepatitis and ulcerative colitis, or uveitis or the presence of an epithelioid granuloma with multinucleated giant cells suggests that in such patients an immunologic disorder might be responsible for the tubulo-interstitial nephritis.

ADAMTS13, the specific von Willebrand factor (VWF)-cleaving metalloprotease, prevents the spontaneous formation of platelet thrombi in the microcirculation by degrading the highly adhesive ultralarge VWF multimers into smaller forms. ADAMTS13 severe enzymatic deficiency and mutations have been described in the congenital thrombotic thrombocytopenic purpura (TTP or Upshaw-Schulman syndrome), a rare and severe disease related to multivisceral microvascular thrombosis. We investigated six French families with congenital TTP for ADAMTS13 enzymatic activity and gene mutations. Six probands with congenital TTP and their family were tested for ADAMTS13 activity in plasma using a two-site immunoradiometric assay and for ADAMTS13 gene mutations using polymerase chain reaction and sequencing. ADAMTS13 activity was severely deficient (5%) in the six probands and one mildly symptomatic sibling but normal (50%) in all the parents and the asymptomatic siblings. Ten novel candidate ADAMTS13 mutations were identified in all families, showing either a compound heterozygous or a homozygous status in all probands plus the previous sibling and a heterozygous status in the parents. The mutations were spread all over the gene, involving the metalloprotease domain (I79M, S203P, R268P), the disintegrin domain (29 bp deletion in intron/exon 8), the cystein-rich domain (acceptor splice exon 12, R507Q), the spacer domain (A596V), the 3rd TSP1 repeat (C758R), the 5th TSP1 repeat (C908S) and the 8th TSP1 repeat (R1096stop). This study emphasizes the role of ADAMTS13 mutations in the pathogenesis of congenital TTP and suggests that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process.

Resume A l’ere des neuroleptiques atypiques, soixante ans apres sa decouverte, l’electroconvulsivotherapie (ECT) demeure un traitement d’actualite dont les conditions pratiques de realisation se sont ameliorees et les indications affinees. Son efficacite dans le traitement des patients schizophrenes a ete l’objet de nombreuses etudes, souvent anciennes, de methodologie heterogene, rendant les donnees et les resultats difficilement comparables. Il existe, neanmoins, un consensus pour recourir a l’ECT chez les schizophrenes lors des exacerbations delirantes, dans la catatonie, les etats schizo-affectifs et en cas de resistance. C’est, le plus souvent, un traitement de seconde intention, apres essai d’une ou plusieurs sequences de neuroleptiques, bien conduites. Dans tous les cas, il est fortement conseille durant la cure d’ECT de maintenir une couverture neuroleptique, avec une molecule conventionnelle ou atypique. Deux modalites therapeutiques d’ECT sont realisees : l’ECT curative et l’ECT de maintenance ou d’entretien, comme l’illustre notre pratique au CHU de Nantes.

Les auteurs rappellent les donnees de la litterature concernant les associations de neuroleptiques dans le traitement de la schizophrenie. Ils decrivent les situations cliniques dans lesquelles les bitherapies neuroleptiques sont les plus frequentes : debut de decompensation. potentialisation changement de neuroleptique, aggravation sous traitement d'action prolongee, resistance averee. Les auteurs soulignent que la bitherapie ne doit jamais etre systematique, mais doit intervenir apres echec d'une strategie centree sur la monotherapie. Ils proposent un arbre decisionnel hierarchisant les strategies therapeutiques lors d'une decompensation schizophrenique.

Aim: The aim of this study was to evaluate the rates and types of drug prescription and administration errors in one pediatric nephrology ward, comparing two dispensing schemes : the first one defined as handwritten prescription plus ward stock distribution system (WSDS), and the second one as computerized prescription plus unit dose drug dispensing system (UDDDS). Method: Data were collected over an 8‐week period, from 1 February to 31 March 1999. Two fifth‐year pharmacy students photocopied prescription and administration documents on the ward each day, under the supervision of a senior pharmacist. The medical record analysis was used to compare the prescription with the administration report. Prescribing and administration medication errors were classified according to the American Society of Health‐System Pharmacists.Results: Prescribing errors: overall, for both dispensing schemes, a total of 511 prescriptions, resulting in 4532 prescribed drugs (an average of 9 drugs per prescription) were prescribed. The total prescription error rate was 20.7% (937 of 4532), resulting in 1.9 errors per patient per day. The computerized prescription error rate was 10.6% (419 of 3943), the handwritten prescription error rate was 87.9% (518 of 589). This difference was very significant (P < 0.0001).Administration errors: the total opportunity of administration errors was 4589 (sum of administered and omitted drugs). The total administration error rate was 23.5% (1077 of 4589) including wrong administration time, and 11.7% (538 of 4589) excluding administration time. The administration error rate, including administration associated with time errors, was only 22.5% (888 of 3943) for computerized prescription + UDDDS, compared with 29.3% (189 of 646) for handwritten prescriptions plus WSDS (P < 0.001). Excluding administration associated with time errors, the administration error rates were 9.7% and 24.3%, respectively (P < 0.0001). Conclusion: The drug prescription and administration error rates were significantly decreased using computerized prescription plus UDDDS as compared with handwritten prescription plus WSDS in a pediatric unit (even with potential biases taken into account).

Resume Chaque annee en France, une centaine d'enfants ont un syndrome hemolytique et uremique (SHU) typique post-diarrhee, la majorite d'entre eux ayant moins de trois ans. L'association a une infection a E. coli producteurs de verotoxines (VTEC), principalement du serotype O157 : H7, est retrouvee dans environ 85 % de cas. Le tableau clinique est caracterise par une phase prodromique comportant une diarrhee souvent sanglante, precedant le SHU de 1 a 15 jours. Le SHU survient brutalement, caracterise par l'association d'une anemie hemolytique avec schizocytes, d'une thrombopenie et d'une insuffisance renale aigue. L'atteinte d'autres organes est possible : colite hemorragique severe avec prolapsus rectal, eventuelle necrose de la paroi colique ou stenose secondaire, pancreatite aigue, atteinte du systeme nerveux central qui conditionne a l'heure actuelle le pronostic vital. La mise en route precoce d'un traitement symptomatique rigoureux permet que le taux de mortalite soit inferieur a 5 %, la plupart des deces etant lies a l'atteinte du systeme nerveux central. Cinq a 10 % des enfants evoluent vers l'insuffisance renale terminale, rarement d'emblee, plus souvent apres recuperation d'une certaine fonction renale avec insuffisance renale chronique pendant quelques annees. Apres 15 annees ou plus de recul, au moins un tiers des patients ont une proteinurie et/ou une hypertension arterielle, eventuellement une insuffisance renale chronique ou terminale. Les elements de mauvais pronostic renal sont, a la phase aigue, une atteinte colique severe, une atteinte du systeme nerveux central, une polynucleose neutrophile superieure a 20 000/mm3, et une duree d'anurie initiale superieure a une semaine. Le role des VTEC fait de cette affection un probleme de sante publique. Les recommandations a visee preventives sont essentielles.

We conducted a study to determine the incidence of haemolytic uraemic syndrome (HUS) in children in France and to assess the role of Shiga-toxin-producing Escherichia coli (STEC) infection in the aetiology of HUS. In collaboration with the Société de Néphrologie Pédiatrique we undertook a retrospective review of all cases of HUS hospitalized from January 1993 to March 1995 and a 1-year prospective study (April 1995–March 1996) of epidemiological and microbiological features of cases of HUS. The polymerase chain reaction (PCR) procedure was used to detect stx, eae, e-hlyA genes directly from case stool samples. Serum samples from cases were examined for antibodies to lipopolysaccharide (LPS) of 26 major STEC serogroups. Two hundred and eighty-six cases were reported. The average incidence per year was 0·7/105 children < 15 years and 1·8/105 children < 5 years. During the prospective study, 122/130 cases were examined for evidence of STEC infection using PCR and/or serological assays and 105 (86%) had evidence of STEC infection. Serum antibodies to E. coli O157 LPS were detected in 79 (67%) cases tested. In conclusion, this study showed that STEC infection is an important cause of HUS in children in France, with a high proportion related to the O157 serogroup.

Background. Between 1967 and 1990, 820 successful pregnancies in 718 women on renal replacement therapy (RRT) were reported to the EDTA Registry. Methods. This study analyses data on repeated successful pregnancies in 102 of these women, of whom 99 had two and three had three pregnancies. Results. Primary renal diseases were mainly glomerulonephritis (41%), pyelonephritis (32%), and congenital malformations such as cystic diseases and hypoplasia or dysplasia (13%). Mean age at start of RRT was 21 years ± 5 SD. Ninety-four per cent of the women had the same transplant during the first and second pregnancies; 85% of these were alive with their first graft and 9% with a second graft ; 4% were retransplanted after the first pregnancy and 2% were back on dialysis during the second pregnancy. Of the mothers with two successful pregnancies, two-thirds had a serum creatinine below 121 μmol/l after the first or after the second pregnancy. Six mothers lost their first graft after the first pregnancy. None of the mothers had died after delivery of the second or third baby. Several features of the first and the second pregnancy in these mothers were quite similar. Mean gestational age was 36 weeks ± 3 SD during first and second pregnancy. Mean birth weight (height) of the first child was 2490 g ± 660 SD (48 cm ± 4 SD) and 2587 g ± 639 SD (50 cm ± 3 SD) of the second child (NS). Neonatal mortality was 4% after the first and second delivery ; congenital abnormalities were found in five and three children respectively. Conclusions. Fourteen per cent of mothers who had a successful pregnancy on RRT subsequently had a second baby. Repeated pregnancies should not adversely affect graft function and/or fetal development provided that graft function was well preserved at the time of conception.

Omenn's reticulosis is an inherited severe combined immunodeficiency characterized by neonatal exfoliative erythroderma. A newborn baby who had minimal change nephrotic syndrome and Omenn's reticulosis is reported. Abnormalities in lymphocyte function could explain both the nephropathy and the cutaneous changes.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) disorder characterised by the association of haemolytic anaemia, thrombocytopenia and acute renal failure. Atypical forms (non-shigatoxin related forms) may be familial or sporadic, frequently with relapses and most of them lead to end stage renal failure. During the last years, different groups have demonstrated genetic predisposition to atypical HUS (aHUS) involving five genes encoding for complement components which play a role in the activation or control of the alternative pathway: encoding factor H (CFH), accounting for 30% of aHUS; CD46 (encoding membrane cofactor protein [MCP]) accounting for approximately 10% of aHUS; CFI (encoding factor I) accounting for an estimated 5-15% of patients; C3 (encoding C3) accounting for approximately 10% of aHUS; and rarely CFB (encoding factor B). Predisposition to aHUS is inherited with incomplete penetrance. It is admitted that mutations confer a predisposition to develop aHUS rather than directly causing the disease and that a second event (genetic or environmental) is required for disease manifestation. HUS onset follows a triggering event in most cases (frequently banal seasonal infection and pregnancy). Uncontrolled C3 convertase leads to increased deposition of C3b on vascular endothelium and participates to the prothrombotic state. The phenotype of aHUS is variable ranging from mild forms, with complete recovery of renal function to severe forms with end stage renal disease within the first year after the onset. Overall, the outcome is severe with a mortality rate of 10% and with more than 60% of patients on dialysis. The most severe prognosis was in the CFH mutation group. There is a high risk of recurrence of the disease after renal transplantation in patients with mutations in CFH, CFI, CFB and C3. Plasma therapy may allow complete haematological remission but frequently with persistent renal damage. Some patients are plasma resistant and some are plasma dependent. The recent progress in the determination of the susceptibility factors for aHUS, have allowed to propose new diagnostic tests including a molecular genetic testing and may permit to consider some new specific treatments in this disease (human plasma-derived CFH or complement inhibitors).

A retrospective study was undertaken of 120 children with systemic lupus erythematosus (SLE) seen in Paris and its immediate suburbs who fulfilled at least four of the American College of Rheumatology diagnostic criteria for SLE, and in whom the disease was diagnosed before the age of 16 and between January 1975 and December 1987. Eleven of these children (eight girls and three boys) all more than 10 years of age (mean follow up 8.1 years; range 3-13) had thrombotic episodes (9%). Thrombosis was one of the presenting signs in seven patients; in five it was associated with typical symptoms of SLE, and in the other two the thrombotic episode was isolated and diagnosis of SLE was delayed one and three years. Of a total of 16 thrombotic episodes (six of which were recurrent), 14 involved the leg veins, and in four there was associated pulmonary embolism. There were two episodes that affected cerebral arteries. The American College of Rheumatology diagnostic criteria for SLE as well as the incidence of lupus anticoagulant, positive direct Coombs test, and vasculitis in this group of patients was compared with the incidence in patients with SLE but no thrombosis. Only lupus anticoagulant was significantly associated with thrombotic episodes: eight of 11 (73%) of patients with SLE and thrombotic (arterial or venous) episodes had lupus anticoagulant compared with only 10 of 74 patients (14%) with no history of thrombotic events in the same age group.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

Although systematic vitamin D supplementation in adolescents remains debated, rickets is nevertheless a well recognized pathology in this age group. Adolescence is an at-risk period because of rapid growth, insufficient calcium intake and/or vitamin D status. Surveys have shown that calcium intake is insufficient (1000 mg a day) in 45% of boys and 71% of girls and that vitamin D status is deficient (25-OH-D10 ng/ml). The aims of the study carried out by the Calcium Group of the Société Française de Pédiatrie, were to evaluate the frequency of rickets, and to define the criteria for the adolescent population at risk. Forty-one adolescents with rickets were hospitalized between 1985 and 2000. Most of the cases were from the Northern France: 20 from Paris and suburbs, eight from the North-West, four from the North, four from the North-East; five were from the Center of France. The mean age was 13 years and two months for the 28 girls, and 14 years and four months for the 13 boys. Eighty per cent of the adolescents were from immigrant families (33/41): 15 were from sub-Saharan Africa, ten from North Africa, six from Pakistan and two from Turkey. Two thirds of the adolescents were hospitalized in the 2nd quarter of the year. Some adolescents suffered from lower limb pain, 16 had deformations of lower limbs, particularly genu valgum, associated with pain; seven others had either muscle spasms (4), tetany (3). Serum calcium level was low (average 1.84 mmol/l: [1.1-2.5]), and serum 25-OH D level was extremely low. Radiographic characteristics observed were metaphyseal strips on the knees, with condensed edges at times, with the presence of bone demineralization. The treatment combined calcium and vitamin D, and was often administered intravenously when a hypocalcemia was detected. Rickets is not frequent in adolescents, but nonetheless this pathology is not exceptional, and the number of cases is probably under-estimated. Rickets affects immigrant adolescents in particular but nevertheless could also present a certain risk period for the general population.

Childhood-onset systemic lupus erythematosus (SLE) is often severe and has a serious long-term morbidity. Pediatric guidelines about its management do not exist. The French study group of childhood-onset SLE proposes recommendations about the investigation which are needed at diagnosis and during follow-up of SLE, in order to adjust the treatment according to the severity of the disease and to avoid unnecessary investigations.

Every year in France, about 100 children, most of them less than 3 years old, have typical diarrhea-associated HUS (D + HUS). Evidence of exposure to verotoxin producing E. coli (VTEC), mostly the O157: H7 serotype, is demonstrated in about 85% of cases. A prodromal illness of acute gastroenteritis with diarrhea, often bloody, precedes the HUS by 1 to 15 days. HUS onset is sudden, with the typical association of hemolytic anemia with fragmented red blood cells, thrombocytopenia and acute renal insufficiency. Involvement of other organs than the kidneys may occur, such as severe hemorrhagic colitis with rectal prolapse, bowel wall necrosis or secondary stenosis, acute pancreatitis, central nervous system involvement which determines the vital outcome. Early accurate supportive treatment allows a current mortality rate below 5%, with most deaths due to central nervous system involvement. Five to 10% of children develop end stage renal disease, rarely directly, more often after having recovered some renal function with chronic renal insufficiency during a few years. After 15 or more years follow-up, at least one third of patients have some degree of proteinuria and/or hypertension, and eventually chronic or end stage renal failure. Predictive features of poor renal outcome at the acute phase are severe gastrointestinal involvement, severe CNS involvement, polyncleosis over 20,000/mm3, and duration of initial anuria longer than one week. The role of VTEC in D + HUS makes the disease a public health problem. Preventive measures are essential.

The diagnosis of chronic renal insufficiency (CRI) must be evoked in children with feeding difficulties, excessive thirst, insufficient weight and/or height gain. Complications of CRI in children are hydroelectrolytic desequilibrium (chronic dehydration, sodium depletion, acidosis), nutritional difficulties, osteodystrophy, growth retardation and psychologic and scolar difficulties. Human recombinant growth hormone treatment generally allows spectacular growth improvement. In children with end-stage renal failure, operation is performed by hemodialysis or, especially in children less than 2 years of age, peritoneal dialysis. Renal transplantation is the best treatment of end-stage renal failure in children, as it offers them a practically normal life, with the only obligation of absorbing medications every day.

To define prospectively the incidence of renal parenchymal lesions in the siblings of patients treated at one institution for primary vesico-ureteric reflux (VUR).From January 1997 to October 1998, a prospective study including renal scintigraphy (using dimercaptosuccinic acid, DMSA) and a radionuclide cystogram was proposed systematically to the asymptomatic siblings of children treated for primary VUR. The radionuclide cystograms were interpreted as showing the presence or absence of VUR and the DMSA scan as symmetrical or asymmetrical differential function, with or with no renal defect.Fifty-five families gave informed consent, of whom 46 completed the study (eight refused secondarily and one was omitted by exclusion criteria), representing 46 symptomatic patients and 65 siblings. There were 17 siblings with VUR (26%) including two of 13 infants and 15 of 52 children aged18 months. One radionuclide cystogram failed. Of the 17 refluxing siblings, four had a history of symptomatic urinary tract infection; 62 of the 65 siblings had a DMSA scan, of which 56 were normal and six (10%) showed abnormalities (five asymmetrical differential function and one parenchymal defect). Only one of these six patients had VUR at the time of the evaluation and only one had a small kidney detected by ultrasonography on one side (and no VUR). There were no adverse effects associated with screening.This study confirms a significant overall incidence of VUR (26%) in the asymptomatic siblings of patients treated for primary VUR. From the results of the DMSA scan (only one sibling had a parenchymal defect), the systematic screening of asymptomatic siblings does not appear to be beneficial.

Azathioprine is a prodrug commonly used in combination therapy to prevent allograft rejection after renal transplantation. After conversion to 6-mercaptopurine, the drug is metabolized into 6-thioguanine nucleotides (6-TGN) and catabolized by thiopurine methyltransferase (TPMT), an enzyme under monogenic control. The aim of this study was to evaluate the inter- and intraindividual variability of red blood cell thiopurine methyltransferase and 6-TGN concentrations and their relationship to the clinical effects of azathioprine in paediatric patients.In the present study, the inter- and intraindividual variations in red blood cell TPMT activity and 6-TGN concentrations and their relationship to the actions of azathioprine were evaluated during the first year after renal transplantation in 22 paediatric patients.6-TGN concentration reached steady-state values after 6 months and correlated negatively with TPMT activity (P=0.004). Initial TPMT activity (median: 20.8 nmol h-1 ml-1, range 7.8-34.6) and 6-TGN concentration at steady-state (median: 80 pmol 8 x 10(8-1) cells, range not detected to 366) were not related to the occurrence of rejection episodes during the period of the study. In contrast, TPMT activity and the percentage difference in TPMT activity from the day of transplantation determined at month 1 were higher in the patients with rejection episodes by comparison with those that did not reject during the first 3 months or the first year following transplantation (P0.005).We report a relationship between TPMT activity and occurrence of rejection in paediatric kidney transplant patients undergoing azathioprine therapy. These data suggest a link between high red blood cell TPMT activity and poor clinical outcome probably caused by rapid azathioprine catabolism.

The cyclosporine microemulsion formulation Neoral, which allows a better absorption and a more regular pharmacokinetic profile, is proposed for replacing the original formulation, Sandimmun. The present study reports the results of conversion from Sandimmun to Neoral in children with a kidney graft, a population for which information remains limited.Twenty children, 2.5 to 10.5 years of age, who had a kidney graft with a stable renal function for between six months to five years (m = 2.6) were the subjects of this study. The patients were switched from Sandimmun to Neoral at the same dose, adjusted afterwards on a cyclosporine trough level.After six months, the mean dose decreased from 9.1 mg/kg/d to 8.4 mg/kg/d, i.e., 12.5%. After one year, the mean dose was 7 mg mg/kg/d, i.e., 28%. Of the 65% of patients who had a decreased dose, most of them had the highest dose of Sandimmun at the start. Mean serum creatininemia levels slightly increased from 85.6 to 89.5 mumol/L after six months (P = 0.03). None of the patients had a rejection crisis during the first six months under Neoral. Blood pressure did not change significantly, hirsutism improved in two cases but increased or appeared in two cases as well. Gingival hypertrophy increased or appeared in four cases.A decrease in the dose was decided on either to maintain the trough CsA blood level in the desired range or because of the appearance of a symptom suggesting a side effect of cyclosporine, especially the increase of creatinemia. The trough level did not appear to be the best index for adapting the dose.In stable pediatric kidney transplant recipients, the switch from Sandimmun to Neoral provided a reduction in drug dosage in 65% of cases without an increase in adverse events.

The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined.We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression.African and Middle East origins, past infection with hepatitis B, hemoglobin level12 g/dl, lymphocyte count750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression.African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Objectif Analyser en microscopie confocale in vivo et en OCT de segment anterieur la cornee de patients atteints de cystinose. Materiels et Methodes Dans cette etude, les dossiers de 4 enfants âges de 7 a 16 ans ayant beneficie d’un examen ophtalmologique complet, d’une analyse de la cornee en microscopie confocale in vivo (Heidelberg Retina Tomograph-Rostock Cornea Module, HRT-RCM) ainsi qu’en OCT de segment anterieur (OCT-Visante®) ont ete retrospectivement analyses. Discussion Tous les patients presentaient des depots hyper-reflectifs correspondant a des cristaux de cystine au niveau de la cornee. En microscopie confocale in vivo, ces cristaux apparaissaient sous la forme de fins depots lineaires hyper-reflectifs d’une longueur variable de quelques microns jusqu’a 100 microns. Ces cristaux ont ete retrouves au niveau de l’epithelium, de la couche de Bowman, du stroma anterieur, du stroma moyen et du stroma posterieur. L’endothelium apparaissait indemne de ces depots. La densite maximale de ces cristaux a ete observee au niveau du stroma anterieur. Les images d’OCT de segment anterieur permettaient egalement de visualiser ces depots au niveau de la cornee et confirmaient leur localisation preferentielle au niveau du stroma anterieur. Cette derniere technique montrait egalement un gradient de depots au sein de la cornee, les cristaux etant plus nombreux au limbe par rapport a la cornee centrale. Conclusion La microscopie confocale in vivo et l’OCT de segment anterieur permettent une analyse a la fois qualitative et quantitative des depots de cristaux de cystine au sein de la cornee. Ces deux techniques d’imagerie peuvent etre utiles lors du suivi de patients atteints de cystinose et notamment pour l’evaluation de nouvelles therapeutiques.

Nephronophthisis is an autosomal recessive tubulointerstitial nephropathy leading to end-stage renal failure during adolescence or early adulthood. Initial symptoms of pitressoresistant polyuria and polydipsia start around 3 years of age, increase over the following years and are often responsible for growth retardation. Renal function declines slowly and end-stage renal failure occurs around 12 years of age in most cases. At ultrasound examination, kidneys have a normal or slightly decreased size, parenchymal echogenicity is increased and the differentiation is reduced. When they are present, medullary cysts are an important feature. Renal biopsy shows atropic or dilated tubules, with irregular thickened basal membranes. Interstitial fibrosis and glomerular sclerosis develop progressively. Various extrarenal abnormalities have been reported in association with nephronophthisis; the most frequent is congenital amaurosis. The most recent advance is the localization of a gene (NPH1) on chromosome 2q13. Deletions in this gene have been shown in about 80% of patients with isolated renal involvement. Such deletions have never been reported when nephronophthisis is associated with congenital amaurosis. The evidence of a deletion in NPH1 gene now allows the diagnosis of nephronophthisis to be performed without renal biopsy. When a delation has been demonstrated in one child, the identification of the deletion in siblings allows to determine those who are affected and those who are not, to propose a reliable prenatal diagnosis.

To evaluate the reliability of Doppler-ultrasonography in identifying children with renal artery stenosis among those with hypertension, we compared Doppler ultrasonography results in 29 hypertensive children (mean age: 8.3 +/- 4.7 years) with angiography. Doppler-ultrasonography and arteriography were performed within a period less than two months. First, we established normal values in 40 normotensive children (mean age: 8.4 +/- 4.5 years). The diagnosis of renal artery stenosis was settled when maximal systolic velocities whereor = to 1.70 m.s-1. Peak systolic velocities values of Doppler-ultrasonography were significantly higher in patients with proven angiographic renal artery stenosis (3.56 +/- 0.70 m.s-1) than in hypertensive patients with normal renal arteries at angiography (1.02 +/- 0.29 m.s-1, p0.0001), and than in normotensive healthy children (1.05 +/- 0.33 m.s-1, p0.0001). We observed 3 false negative and 2 false positive diagnoses with Doppler-ultrasonography. Of the 3 false negatives, one had a stenosis on a right and posterior segmental artery and the other had bilateral and multiply intra-renal artery stenosis with few hemodynamic significance. The 2 false positives were due to a sinuous main renal artery and to a technical mistake, respectively. In another patient, Doppler-ultrasonography revealed a tight main renal artery stenosis, not detected by arteriography. Renal artery stenosis was subsequently confirmed by a second arteriography. Our results showed a sensitivity of 88%, a specificity of 93%, a positive predictive value of 92% and a negative predictive value of 89%, demonstrating the reliability of Doppler-ultrasonography for the diagnosis of renal artery stenosis in hypertensive children. With the use of a rigorous methodology and the increasing experience of the operators, diagnostic errors of renal artery stenosis are currently avoidable. Nevertheless, it is not excluded that intra-renal artery stenosis with few hemodynamic significance might be missed by Doppler-ultrasonography.

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Patients with chronic renal failure are at risk of vitamin A intoxication, a risk that must be evoked when unexplained hypercalcemia occurs.An 8 year-old boy with Alagille syndrome and chronic renal failure was admitted because of general deterioration, and bone pain. Severe hypercalcemia (3.9 mmol/L) was present. Serum phosphate, parathyroid hormone and 25 OH D3 levels were normal; 1-25 (OH)2 D3 levels were undetectable. Hypercalcemia was attributed to vitamin A intoxication, due to the administration of a mean daily dose of 12000 IU of vitamin A for at least 2 years. The diagnosis was confirmed by high plasma levels of retinol (1475 micrograms/L). Hypercalcemia only partially responded to treatment with bisphosphonates, calcitonin and dialysis with low calcium dialysate. Serum vitamin A levels remained elevated one month after vitamin A withdrawal. The boy died two months after admission from atrioventricular block.Vitamin A administration induces a high risk of intoxication in patients with chronic renal failure. Serum vitamin A concentrations are elevated in these patients, because of decreased renal metabolism of retinol, and vitamin A supplements must be avoided.