[Eosinophilic cystitis in children]. / Cystite à éosinophiles chez l'enfant.

Eosinophilic cystitis (EC) is a rare disease that frequently suggests a bladder tumour at presentation. It affects both children and adults and its pathophysiology remains unclear. EC usually shows a benign course, but serious complications can occur and relapsing forms have been described. It has rarely been reported in children and therefore, might be poorly known by physicians and underdiagnosed. We report a case that differs from other observations by its unusually rapid resolution, and review the literature on EC's diagnosis, treatment, and course in children.

[Impact of fetal urinary ascites on serum beta2 microglobuline in obstructive uropathies: a case report]. / Impact de l'ascite urinaire foetale sur le taux de beta2 microglobuline sérique dans les uropathies obstructives : à propos d'un cas.

We report a posterior urethral valves case diagnosed at 33 week's gestation on a fetus presenting with anamnios and urinary ascites. In this fetus, the serum beta2 microglobuline rate was high, suggesting a very poor renal prognosis. At 1-year-old, the creatinine rate is nearly normal. In case of urinary ascites, the serum beta2 microglobuline rate could be improved in relation with the transperitoneal reabsorption of this protein.

[Stop of antibiotic prophylaxis in mild/moderate grade vesico-ureteral reflux]. / Arrêt de l'antibioprophylaxie urinaire dans les reflux vésico-urétéraux de grade I, II ou III.

UNLABELLED: Vesicoureteric reflux (VUR) is found in about 30 % of children with pyelonephritis (PN). It has been identified as a risk factor for the development of urinary tract infections, renal scars, hypertension and chronic renal failure but this risk is considerably smaller than previously assumed. Currently the therapeutic option was to use an antibiotic prophylaxis in order to keep the urinary tract sterile in order to prevent pyelonephritis and new renal scars. The review of the available data has shown that the antibiotic prophylaxis therapy is subject to discussion. The aim of this study was to evaluate the follow up of children with low-grade reflux before and after stopping the urinary antibiotic prophylaxis as soon as they became toilet-trained. METHODS: Fifty-eight children with low-grade reflux (grade I, II, III) were enrolled in this study. The follow up ranged from October 2002 till February 2007. The children who have not attained bladder control received antibiotic prophylaxis. This treatment was stopped as soon as they became toilet-trained. The presence of urinary tract infection (UTI) was considered in case of unexplained fever and urinalysis and urine culture were performed. RESULTS: VUR, mainly grade II, was discovered at a median age of 16 months. The prophylaxis was stopped at a median age of 40 months. The follow up after stopping the antibacterial prophylaxis was 27 months. Under treatment 2 pyelonephritis occurred, without treatment 2 pyelonephritis and 3 cystitis were diagnosed. At the end of the follow up, the grade of reflux decreased in half of the cases and disappeared in 3 cases. CONCLUSION: By stopping the urinary antibiotic prophylaxis in children with mild/moderate grade VUR when they became toilet-trained, there is no increase of the incidence of UTI, pyelonephritis. This study does not support the role for urinary antibiotic prophylaxis in preventing the recurrence of pyelonephritis.

Population pharmacokinetics and pharmacogenetics of tacrolimus in de novo pediatric kidney transplant recipients.

The aim of this study was to develop a population pharmacokinetic model of tacrolimus in pediatric kidney transplant patients, identify factors that explain variability, and determine dosage regimens. Pharmacokinetic samples were collected from 50 de novo pediatric kidney transplant patients (age 2-18 years) who were on tacrolimus treatment. Population pharmacokinetic analysis of tacrolimus was performed using NONMEM, and the impact of variables (demographic and clinical factors, and CYP3A4-A5, ABCB1, and ABCC2 polymorphisms) was tested. The pharmacokinetic data were described by a two-compartment model that incorporated first-order absorption and lag time. The apparent oral clearance (CL/F) was significantly related to body weight (allometric scaling); in addition, it was higher in patients with low hematocrit levels and lower in patients with CYP3A5*3/*3. The population pharmacokinetic-pharmacogenetic model developed in de novo pediatric kidney transplant patients demonstrated that, in children, tacrolimus dosage should be based on weight, hematocrit levels, and CYP3A5 polymorphism. Individualization of therapy will enable the optimization of tacrolimus exposure, with resultant beneficial effects on kidney function in the initial post-transplantation period.

Successful anti-TNFalpha treatment in a child with posttransplant recurrent focal segmental glomerulosclerosis.

Posttransplant recurrence of focal and segmental glomulosclerosis (FSGS) occurs in approximately 30% of patients, and remains after uncontrolled despite increased immunosuppression and plasma exchanges (PE) in approximately 30% of cases. New immunosuppressive drugs might then be warranted. We report the case of a 15-year-old boy with FSGS leading to end-stage renal disease (ESRD) who presented with an early posttransplant recurrence of disease. Reinforced immunosuppression and PE resulted in partial and transient disease control, but proteinuria significantly decreased with anti-TNFalpha treatment (infliximab then etanercep). This is the first case report of successful anti-TNFalpha treatment despite a constant high activity of FSGS, as demonstrated by relapse after discontinuation of anti-TNFalpha agents.

[Abnormalities of hepatocyte nuclear factor (HNF)-1beta: biological mechanisms, phenotypes, and clinical consequences]. / Les anomalies de l'hepatocyte nuclear factor (HNF)-1beta : mécanismes biologiques, phénotypes et conséquences cliniques.

The hepatocyte nuclear factor-1beta encoded by the TCF2 gene plays a role in the specific regulation of gene expression in various tissues such as liver, kidney, intestine, and pancreatic islets and is involved in the embryonic development of these organs. TCF2 mutations are known to be responsible for maturity-onset diabetes of the young type 5, associated with renal manifestations. Several studies have shown that TCF2 mutations are involved in restricted renal phenotypes. In a recent study, TCF2 anomalies were detected in one third of patients with renal anomalies such as renal cysts, hyperechogenicity, hypoplasia, or single kidneys. Most patients have a complete deletion of the TCF2 gene. With de novo TCF2 anomalies, deletions were the most frequent anomaly. TCF2 anomalies were significantly associated with bilateral renal anomalies and bilateral cortical cysts. However, no genotype-phenotype correlation could be detected. The prenatal phenotype of TCF2 anomalies is mainly bilateral hyperechogenic kidneys. Abnormal renal function, detected in about one third of patients, was independent of the TCF2 genotype. The best parameter to predict renal outcome remains sonographic evaluation. However, progression of the TCF2 phenotype is common. In conclusion, TCF2 molecular anomalies are involved in restricted renal phenotype in childhood without alteration of glucose metabolism. Adequate metabolic follow-up of pediatric patients with a restricted renal phenotype has not yet been defined and consideration of prenatal diagnosis remains extremely difficult given the extremely large phenotypic variability within the same family.

Rituximab therapy for childhood-onset systemic lupus erythematosus.

OBJECTIVE: To describe the safety and efficacy of rituximab in the treatment of childhood-onset systemic lupus erythematosus (SLE). STUDY DESIGN: We conducted a French multicenter retrospective study of childhood-onset SLE treated with rituximab. RESULTS: Eleven girls with severe SLE, including 8 girls with class IV or V lupus nephritis, 2 girls with severe autoimmune cytopenia, and 1 girl with antiprothrombin antibody with severe hemorrhage, were treated with rituximab. The mean age at onset of rituximab treatment was 13.9 years. Patients received 2 to 12 intravenous infusions of rituximab (350-450 mg/m2/infusion), with corticosteroids. Six patients also received different standard immunosuppressive agents, including Cyclophosphamide (2 patients). Remission was achieved in 6 of 8 patients with lupus nephritis and in the 2 patients with autoimmune cytopenia. Steroid therapy was tapered in 5 patients who responded to treatment, and low-dose prednisone treatment was maintained in 1 patient. The mean follow-up period was 13.2 months (range, 6-26 months), and remission lasted in all who patients who responded to treatment, except 1 patient who was successfully retreated with a second course of rituximab. Anti-double-stranded DNA antibody levels decreased in 6 of 11 patients, and anticardiolipin antibody levels decreased in 3 of 4 patients. Severe adverse events developed in 5 patients. Effective depletion of peripheral blood B cells was observed in 7 of 8 patients who were examined, and this paralleled the remission. CONCLUSION: Rituximab may be an effective co-therapy; however, further investigations are required because severe adverse events occurred in 45% of the patients in this study.

From humoral rejection to generalized thrombotic microangiopathy--role of acquired ADAMTS13 deficiency in a renal allograft recipient.

A 9-year-old renal transplant recipient presented with elevated serum creatinine levels 4 years post-transplant renal biopsy revealed humoral rejection including lesions suggestive for thrombotic microangiopathy (TMA). He received methylprednisolone pulses followed by a normalization of serum creatinine. Two more steroid responsive acute rejection episodes occurred. Two months later he presented rapidly progressive life threatening symptoms including bilateral pyramidal syndrome and hemoptysis. Serum haptoglobin became undetectable at this time and platelet count decreased (70000/microl), suggesting TMA. Cerebral MRI revealed generalized ischemic white matter lesions. ADAMTS13 activity decreased to < 5%. Daily plasma exchanges (PE) resulted in immediate improvement. All attempts to discontinue PE were unsuccessful. Transplantectomy resulted in normalization of generalized symptoms, hemolysis and ADAMTS13 activity (110%). Multi-organ involvement has never been reported in acquired ADAMTS13 deficiency post-transplant. Rapid resolution after transplantectomy might suggest that renal TMA was responsible for acquired ADAMTS13 deficiency and thereby triggered the generalization of TMA lesions.

Population pharmacokinetics of mycophenolic acid in kidney transplant pediatric and adolescent patients.

Current data on mycophenolate mofetil (MMF) suggest that there is a pharmacokinetic/pharmacodynamic relationship between the mycophenolic acid (MPA) area under the curve (AUC) during treatment and both the risk of acute rejection and the occurrence of side effects. The aim of this study was to characterize the population pharmacokinetics of MPA in kidney transplant patients between the ages of 2 and 21 years and to propose a limited sampling strategy to estimate individual MPA AUCs. Forty-one patients received long-term oral MMF continuous therapy as part of a triple immunosuppressive regimen, which also included cyclosporine or tacrolimus (n=3) and corticosteroids. Therapy was initiated at a dose of 600 mg/m twice daily. The population parameters were calculated from an initial group of 32 patients. The data were analyzed by nonlinear mixed-effect modeling using a 2-compartment structural model with first-order absorption and a lag time. The interindividual variability in the initial volume of distribution was partially explained by the fact that this parameter was weight-dependent. Fifteen concentration-time profiles from 13 patients were used to evaluate the predictive performance of the Bayesian approach and to devise a limited sampling strategy. The protocol, involving two sampling times, 1 and 4 hours after oral administration, allows the precise and accurate determination of MPA AUCs (bias -0.9 microg.h/mL; precision 6.02 microg.h/mL). The results of this study combine the relationships between the pharmacokinetic parameters of MPA and patient covariates, which may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care.

[Renal complications of non-steroidal anti-inflammatories]. / Complications rénales des anti-inflammatoires non stéroïdiens.

INTRODUCTION: Non-steroidal antiinflammatory drugs (NSAIDs) are known to have adverse effects on kidney function. Situations with stimulated renin-angiotensin system (RAS) like volume depletion or preexisting chronic renal failure predispose to acute renal failure (ARF) via inhibition of prostaglandin synthesis by NSAIDs. To date NSAIDs are frequently used as antipyretic drugs even in situations predisposing to ARF. PATIENTS: Within 20 months seven children presenting with diarrhea and/or vomiting and fever were treated with therapeutic doses (11.5-32 mg/kg per day) of ibuprofen for 1-3 days before developing ARF. Maximum plasma creatinine levels were 180-650 pmol/l. One patient required emergency dialysis for hyperkalemia, uremia, and hyperphosphatemia. After cessation of NSAID treatment and rehydration all patients recovered completely with a normalized creatinine level after 3-9 days. Once the acute phase is controlled long-term outcome is excellent. CONCLUSION: NSAIDs are potentially dangerous in situations with, even moderate, volume depletion.

[Alkaptonuria: a rare cause of urine discoloration. Report of a case in a newborn]. / L'alcaptonurie: une cause rare de coloration anormale des urines. A propos d'un cas chez le nourrisson.

UNLABELLED: Alcaptonuria is a rare hereditary disease, characterized by an abnormal blackish coloration of the urine and dark pigmentation of the conjunctive tissue which is due to a deficiency in homogentisate 1,2-dioxygenase (HGO), a phenylalanine catabolizing enzyme. An accumulation of homogentisate (HGA) is then formed, and is responsible for the dark coloration which only occurs after the urine has been exposed to air over a period of time. Signs of this disorder therefore frequently remain unnoticed during childhood, because the urine requires a relatively long exposure to air before it changes color. Diagnosis is generally made at a later date, during adulthood, following complications such as ochronosis, inflammatory arthritis, or urinary calculi. CASE REPORT: In this study, the case has been described of alcaptonuria diagnosed in a five-month old infant. No efficient cure has yet been found, although certain treatments, including high doses of vitamin C, do seem to have a beneficial effect on limiting the complications associated with this disorder. Early diagnosis whenever possible is therefore important. CONCLUSION: This case report is interesting because of the early diagnosis involved. In the event of any abnormal coloration of the urine, diagnosis may be established via the addition of an alkylating agent, and the levels of HGA determined by chromatography.