[Proteinuria and (or) hematuria in children. Diagnostic orientation].
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Biomedical subjects
Publications and source records attributed to P Cochat.
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OBJECTIVES: Evaluate bacterial infection epidemiology and pathophysiology in children with nephrotic syndrome. METHODS: From January 1983 to December 1992, 399 children with the nephrotic syndrome were admitted in 3 University Pediatric wards (Paris Enfants Malades, Lyon Edouard Herriot, Lyon Debrousse). Severe bacterial infection was diagnosed when the patient's condition has justified an intravenous antibiotherapy. RESULTS: Forty-eight bacterial infections were noted in 32 patients (8%); the infection was the first symptom of the disease in 10 patients (31%); one patient died shortly after admission. Severe bacterial infection concerned steroid-resistant nephrotic syndrome in 13 cases (41%), but only 7 out of them received immunosuppressive agents at the time of the infection. Eleven children (34%) experienced recurrent infections (1 to 6 recurrences), several of which under antibioprophylaxy. Half of the infections involved peritonitis and 50% of the identified germs were S. pneumoniae. However, peritonitis was not always related to S. pneumoniae (1 H. influenzae among 9 identified germs). CONCLUSIONS: These data demonstrate the importance of microbiological sampling and justify a first-line antibiotherapy using a third generation cephalosporin. The presentation of severe bacterial infections show that it is less a iatrogenic event than a consequence of immunological disturbances induced by the nephrotic syndrome itself, as suggested by the acquired deficiency of factor I and B. Despite recent advances in antibiotic strategies responsible for a significant reduction in the severity of such infections (1 death among 32 patients), preventive treatments are quite disappointing.
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Bedwetting is present in 5 to 7% of children aged 7 to 8 years. The history of the disorder and the examination of the child are of main importance. This is usually the first step to identify nocturnal enuresis, bladder or urethral instability and other voiding dysfunctions. Therapeutic failure is often related to an inadequate analysis of the disorder. For nocturnal enuresis, the best results are obtained with alarms and/or desmopressine; bladder instability usually requires oxybutinine chlorydrate and urethral instability can be treated with biofeedback therapy. The management of other voiding dysfunctions depends on urodynamic assessment.
The financial cost of bedwetting management is often underestimated. A study including 48 children aged 6 to 16 years was carried out in the outpatient clinic in order to evaluate the cost of these disorders during a 4 month-period. The diagnosis was the following: nocturnal enuresis (n = 15), bladder instability (n = 22) and other voiding dysfunction (n = 11). Our results showed that these expenses were quite important. A relationship between the kind of voiding dysfunction and the subsequent expenses was observed: the more complex was the disorder, the more expensive it was (average expenses = 1317 FF/year for nocturnal enuresis, 2506 FF/year for bladder instability and 3174 FF/year for other dysfunctions). Subsidiary expenses (transport, diapers and extrawashing) constituted an important part of the whole expenses: 46% in nocturnal enuresis, 42% in bladder instability and 38% in other dysfunctions.
Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.
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Peritoneal dialysis, continuous hemofiltration (HF) and continuous hemodiafiltration (HDF) are the most convenient methods for blood purification in pediatric intensive care units. HF is based on the ultrafiltration process and removes not only water but also Na, K, bicarbonate, urea and creatinine with sieving coefficient close to 1. HDF is based on both ultrafiltration and diffusion processes and increases the removal of low molecular weight solutes (urea). These procedures are indicated in: 1) neonates presenting with oligo-anuric acute renal failure (ARF) or fluid overload withstanding diuretics or some metabolic diseases; 2) children presenting with ARF, fluid overload or some metabolic disorders, poisonings or shocks.
Although urinary tract infections are of particular concern in young children, as they may lead to permanent health problems, there is no consensus for their acute management. We carried out a mailed survey of 455 general practitioners, 143 paediatricians (randomly selected from a list of physicians in the Rhône-Alpes region of France) and 45 paediatric nephrologists (all the members of the "Société de Néphrologie Pédiatrique") to examine their attitudes to the management of a fictitious case of a young girl with symptoms indicative of acute pyelonephritis. The responses given by the general practitioners and paediatricians were similar, whereas those given by the paediatric were similar, whereas those given by the paediatric nephrologists were often different, for example 20% of the general practitioners and 17% of the paediatricians said they would hospitalize the child, compared with 69% of the paediatric nephrologists. The majority of the general practitioners and paediatricians favoured single oral antibiotic therapy, whereas the paediatric nephrologists were split between single and combined antibiotic therapy, but preferred intravenous administration. The most frequently prescribed drug was a penicillin. The heterogeneity of the results from this survey stresses the need for the assessment of various strategies in terms of their efficacy for preventing kidney scarring and their risk-to-benefit ratios in well-designed randomised controlled trials.
Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume-corrected BMD were observed 6 months after renal transplantation (p < 0.05, p < 0.01, and p < 0.01 respectively); the median loss of BMD and spine volume-corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement.
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Small children have often been reported to have poor outcome after kidney transplantation (KT). Recent reports from North America have shown that the use of living-related donors improves patient and graft survival. We report the experience in one centre of primary cadaveric KT using sequential immunosuppression in nine children aged 8-30 months and weighing 5.4-9.8 kg; donors were 0.7-12.3 years old. Four patients had pre-emptive KT and the other five were on peritoneal dialysis; the mean +/- SD waiting time was 2.0 +/- 2.4 months. Perioperative care has been published previously. The surgical approach was intraperitoneal if the aorta and vena cava were used (n = 7) and extraperitoneal for common iliac vessels anastomosis (n = 2); the duration of surgery was 3.5 +/- 0.9 h and the time for vascular anastomosis was 32 +/- 6 min. The recipients received ATG, azathioprine, prednisone and delayed administration of cyclosporin A. The patients were followed for 12-98 (median 41) months and showed good graft function (inulin clearance 63-100 ml/min/1.73 m2); only one child with recurrent haemolytic uraemic syndrome lost his graft three months post-transplantation and died after he had received a second graft. None of the recipients required post-transplant dialysis; arterial hypertension involved four children and was related to graft artery stenosis in two. Growth improved by 0.24 +/- 0.48 SD score of height per year.(ABSTRACT TRUNCATED AT 250 WORDS)
Several reports emphasize the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on renal function. We have observed over the last 10 years seven cases of acute renal failure (ARF) due to immune interstitial nephritis in children. A recommended oral or rectal dose of niflumic acid was prescribed for ear-nose-throat disorders. Length of exposure was 1-5 days. Clinical symptoms (oedema, oliguria or anuria) appeared between 3 and 6 days. Three patients had previously received the drug. Hypersensitivity signs (fever, skin rash, eosinophilia, and/or increased IgE) were present in all cases, leukocyturia in five cases, and haematuria in six cases. Renal biopsy showed interstitial lesions with lymphocyte, eosinophil, and plasma cell infiltrates without tubular cell necrosis. Glomeruli were normal on light-microscopy, except in one patient. Electron-microscopy showed extensive podocyte fusion in two patients, who had clinical and laboratory evidence of nephrotic syndrome (NS). ARF rapidly disappeared after NSAID withdrawal, except in two patients whose renal failure was irreversible despite methylprednisolone bolus. ARF is very rare in children treated with niflumic acid. When ARF occurs, different pathophysiological mechanisms are involved but the most common is immunological.
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Type 1 is the most common form of primary hyperoxaluria, also called oxalosis when systemic involvement has occurred. This recessive autosomal inherited inborn error of metabolism is characterized by a defect of alanine: glyoxylate aminotransferase (AGT), which is a specific liver enzyme. This protein is responsible for glyoxylate detoxification only when it is located in the peroxisome. The clinical and biochemical phenotypes are neither correlated with the residual catalytic activity of AGT nor with its immunoreactivity. Most patients display less than 2% catalytic activity (enz-) or no immunoreactive protein (crm-); peroxisome-to-mitochondrion mistargeting is the main feature of patients crm+/enz+ or crm+/enz-. The cDNA and genomic DNA have been cloned and sequenced and the gene has been located on the long arm of chromosome 2 in the q36-37 region. Three polymorphisms have been identified which are preferentially associated, leading to two alleles; six point mutations have been currently reported.
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Assessment of renal function in children raises several difficulties concerning technical and analytical aspects. Renal function parameters are influenced by both age and renal failure. Inulin clearance is the standard method to measure glomerular filtration rate, but it cannot be routinely used. Among other methods, plasma creatinine determination is not reliable to evaluate the level of renal function or to follow the course of renal diseases. Creatinine clearance estimated from calculations such as Schwartz formula does not provide an accurate estimation of the glomerular filtration rate. More precise estimate can be obtained from endogenous creatinine clearance, providing that the measurement is performed accurately. In this paper the authors review these factors and report personal data obtained from 500 children who underwent renal function investigation.