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Biomedical subjects

C Loirat

Publications and source records attributed to C Loirat.

At least 19 recordsLinked to original sources
PubMed2001

[Chronic renal insufficiency in children].

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.

Adolescent↗
PubMed2001

Organ allocation in pediatric transplantation in France.

In France, ministerial decrees in 1995 and 1996 gave children under 16 who are awaiting transplantation national priority for kidneys and livers from donors under 16, and regional priority for kidneys and livers from donors under 30. We analyzed the effects of these changes on waiting time, death on the waiting list, and balance between demand and supply. The percentage of children who received a transplant during the year of registration increased from 40% in 1993 to 67% in 1998 for kidney transplantation, but only from 50% to 67% for liver transplantation. The number of new children registered on the renal transplant waiting list (84 in 1998) and the number transplanted (85 in 1998) are balanced. But, because of the number of children still on the waiting list at the end of each year, there remains an imbalance of about 70 for kidney transplantation. For liver transplantation, there remains an imbalance of about 35. Death on the renal transplant waiting list has been below 2% since 1993. Death on the liver transplant waiting list decreased from 10-20% in 1993-1995 to 3% in 1998. The number of children who died on the thoracic organ waiting list in 1998 was the same as the number transplanted. In conclusion, the new rules governing organ allocation to children in France have shortened waiting time for renal transplantation, but not for liver transplantation. Many children still die on the waiting list for thoracic organ transplantation.

Adolescent↗
PubMed2001

[Post-diarrhea hemolytic-uremic syndrome: clinical aspects].

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.

Child↗
PubMed2001

Scintigraphic screening for renal damage in siblings of children with symptomatic primary vesico-ureteric reflux.

OBJECTIVE: To define prospectively the incidence of renal parenchymal lesions in the siblings of patients treated at one institution for primary vesico-ureteric reflux (VUR). PATIENTS AND METHODS: 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. RESULTS: 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 aged > 18 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. CONCLUSION: 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.

Adolescent↗
PubMed2001

Multicenter trial of one HLA-DR-matched or mismatched blood transfusion prior to cadaveric renal transplantation.

BACKGROUND: The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood donor and recipient. METHODS: In this prospective study, 144 naive patients were randomly assigned to receive one unit of blood matched for one-HLA-DR antigen (N = 49), or one unit of mismatched blood (N = 48), or to remain untransfused (N = 47). Graft survival and acute rejection rate were analyzed in 106 cadaveric renal allograft recipients receiving the same immunosuppressive protocol. RESULTS: Graft survival was similar in the three groups at one and five years: 91.7 and 80% in untransfused patients, 90.3 and 79.3% in patients transfused with one DR-antigen-matched unit, and 92.3 and 83.7% in patients transfused with HLA-mismatched blood. The difference in the incidence of six-month post-transplant acute rejections was not statistically significant in the three groups: 12 out of 36, 33.3% in nontransfused patients; 6 out of 31, 19.4% in patients transfused with one DR-matched blood; and 13 out of 39, 33.3% in patients transfused with mismatched blood. CONCLUSION: The results of our prospective randomized trial showed that in a population of naive patients, one transfusion mismatched or matched for one HLA-DR antigen given prior to renal transplantation had no significant effect on the incidence and severity of acute rejection, and did not influence overall long-term graft outcome. Considering the potentially deleterious adverse effects of blood transfusions, the costs, and the considerable logistical efforts required to select and type blood donors, such a procedure cannot be recommended in a routine practice for patients awaiting cadaveric kidney transplantation.

Acute Disease↗
PubMed2000

Pharmacokinetics and tolerance of mycophenolate mofetil in renal transplant children.

Mycophenolate mofetil (MMF) is a prodrug that is hydrolyzed to the active immunosuppressant mycophenolic acid (MPA). The drug is now widely prescribed for adult renal transplant recipients and its use has been extended to pediatric patients, although pharmacological data in this age group are limited. Nine pediatric renal transplant recipients received MMF with corticosteroids and either cyclosporine or tacrolimus a median of 55 months (range 7.5-124 months) months after transplantation. The pharmacokinetic parameters of MPA and MPA glucuronide (MPAG) were determined at steady state by high-performance liquid chromatography after administration of MMF at the oral dose of 494+/-142 mg/m(2) twice daily. MPA was rapidly absorbed, with a peak concentration at 1.4 h. The mean plasma concentration of MPA at steady state was 4.7+/-1.3 microg/ml. The areas under the plasma concentration-time curves (AUCs) over 12 h (between two administrations) were 57.0+/-15.3 microg.h/ml for MPA and 1,515+/-722 microg.h/ml for MPAG, and the apparent oral clearance was 11.7+/-7.0 and 0.5+/-0.4 l/h for MPA and MPAG, respectively. Assuming that the pharmacokinetics of MPA was dose dependent, the mean concentration at steady state and the AUC for MPA were calculated for the recommended dosage schedule of 600 mg/m(2) every 12 h and were 6.3+/-2.7 microg/ml and 75.2+/-32.9 microg.h/ml, respectively. The tolerance of MMF was studied prospectively with a follow-up of 1.1+/-0.2 years. Gastrointestinal disorders requiring dosage reduction or discontinuation of therapy, observed in five of nine patients, occurred at an incidence higher than expected from adult data. Our results suggest that the dose of 600 mg/m(2) every 12 h extrapolated from adult data for use in pediatric patients would be associated with plasma levels and AUCs higher than expected and may be associated with a higher incidence of side-effects, primarily gastrointestinal.

Abdominal Pain↗
PubMed2000

Haemolytic uraemic syndrome and Shiga toxin-producing Escherichia coli infection in children in France. The Société de Néphrologie Pédiatrique.

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 0.7/10(5) children < 15 years and 1.8/10(5) 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.

Adhesins, Bacterial↗
PubMed2000

WT1 splice-site mutations are rarely associated with primary steroid-resistant focal and segmental glomerulosclerosis.

BACKGROUND: Donor splice-site de novo heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) have been reported in Frasier syndrome, which is defined by the association of focal and segmental glomerulosclerosis (FSGS), male pseudohermaphroditism, and gonadoblastoma. These splice-site mutations alter the WT1 alternative splicing leading to two WT1 isoforms, with (+) or without (-) three amino acids, lysine-threonine-serine (KTS), between zinc fingers 3 and 4. The aim of this work was to investigate the possibility that some cases of primary steroid-resistant nephrotic syndrome associated with FSGS may be caused by WT1 splice-site mutations. METHODS: We analyzed WT1 exons 8 and 9 and the surrounding exon/intron boundary DNA sequences in 37 children with nonfamilial primary steroid-resistant nephrotic syndrome. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the relative ratio of +KTS/-KTS transcripts from immortalized lymphocyte RNA. RESULTS: One boy with FSGS and associated pathologies (diaphragmatic hernia, proximal hypospadias, and unilateral testicular ectopia) was found to carry the heterozygous 1228 +4 C-->T splice-site mutation. RT-PCR quantitation of the +KTS/-KTS transcripts from immortalized lymphocyte RNA of this patient showed a diminution of the +KTS/-KTS isoform ratio (0.43), which is identical to that reported in patients with Frasier syndrome. Using the same approach, healthy control subjects have +KTS/-KTS ratios ranging from 1.50 to 2.00. CONCLUSIONS: This study expands the range of the phenotypic presentation of the intron 9 splice-site WT1 mutations and adds to the already reported heterogeneity of primary steroid-resistant nephrotic syndromes. We suggest that these mutations are not likely to be a common cause of isolated steroid-resistant nephrotic syndrome, and recommend a WT1 exon 9/intron 9 splice-site study in children with primary steroid-resistant nephrotic syndrome if genital or diaphragmatic anomalies are associated. The identification of such WT1 mutations has practical implications for the management of these patients.

Adolescent↗
PubMed2000

Effect of individual plasma lipoprotein(a) variations in vivo on its competition with plasminogen for fibrin and cell binding: An in vitro study using plasma from children with idiopathic nephrotic syndrome.

Simultaneous natural changes in lipoprotein(a) [Lp(a)] and plasminogen occur in the nephrotic syndrome and offer a unique opportunity to investigate their effects on plasminogen activation under conditions fashioned in vivo. Plasminogen, Lp(a), and apolipoprotein(a) in plasma were characterized, and their competitive binding to carboxy-terminal lysine residues of fibrin and cell membrane proteins was determined in nephrotic children during a flare-up of the disease (61 cases) and after 6 weeks (33 cases) and 6 months (42 cases) of remission. Low plasminogen concentrations (median 1.34 micromol/L, range 0.39 to 1.96 micromol/L) and high Lp(a) levels (median 0.27 g/L, range 0.07 to 2. 57 g/L) were detected at flare-up. These changes were associated with an increased Lp(a) binding ratio onto fibrin (3.13+/-0.48) and cells (1.53+/-0.24) compared with binding ratios of control children (1.31+/-0.19 and 1.05+/-0.07, respectively) with normal plasminogen and low Lp(a) (median 0.071 g/L). After 6 weeks and 6 months of remission, the values for net decrease in Lp(a) binding to fibrin were 1.7+/-0.22 (after 6 weeks) and 1.88+/-0.38 (after 6 months) and were correlated with low Lp(a) concentrations (median 0.2 g/L, range 0.07 to 0.8 g/L; and median 0.12 g/L, range 0.07 to 1.34 g/L) and inversely associated with increased plasminogen levels (median 1.82 micromol/L, range 1.4 to 2.1 micromol/L; and median 1.58 micromol/L, range 1.1 to 2.1 micromol/L). These studies provide the first quantitative evidence that binding of Lp(a) to lysine residues of fibrin and cell surfaces is directly related to circulating levels of both plasminogen and Lp(a) and that these glycoproteins may interact as competitive ligands for these biological surfaces in vivo. This mechanism may be of relevance to the atherothrombotic role of Lp(a), particularly in nephrotic patients.

Adolescent↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: 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. METHODS: 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. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/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 (P<0.00001). 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. CONCLUSION: 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.

Adult↗
PubMed1999

Renal granulomatous sarcoidosis in childhood: a report of 11 cases and a review of the literature.

UNLABELLED: We analysed retrospectively 11 children with renal granulomatous sarcoidosis confirmed by renal histology in order to describe the course and prognosis of the disease. Symptomatic sarcoidosis was diagnosed at a mean age of 10.1 years. Nine children had renal involvement at the time of diagnosis. In the course of the disease, nine patients developed renal failure and mild proteinuria, seven had transient sterile leukocyturia, four showed microscopic haematuria, seven had a urinary concentrating defect, and enlarged kidneys were seen in three patients. One child had hypercalcaemia and hypercalciuria, none had hypertension. Light microscopy of the kidney showed interstitial infiltration by mononuclear cells in all children, interstitial fibrosis in nine patients, epithelioid granulomas in seven, tubular involvement in eight, and mild glomerular involvement in seven patients. Renal immunofluorescence was negative. Ten children received prednisone for 1-11 years. After a mean follow up of 5.5 years, three patients had entered end-stage renal failure and one had chronic insufficiency after interruption of medical supervision and prednisone therapy. CONCLUSION: Renal failure, proteinuria, leukocyturia, haematuria, and concentration defect are the prominent features of renal granulomatous sarcoidosis in children. Steroid therapy, adjusted according to disease activity, may prevent end-stage renal failure.

Adolescent↗
PubMed1999

Post graft development of short children treated with growth hormone before kidney graft.

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6+/-1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3. 5+/-1.4 years. During treatment, mean height increased from -3.0+/-0. 9 standard deviation score (SDS) to -1.9+/-1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1. 2+/-0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5+/-0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: -0.5+/-0.4 SDS in patients grafted at early stages of puberty (P2-P3) and -0.15+/-0.9 SDS in patients grafted at late stages of puberty (P4-P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children.

Age Factors↗