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P Niaudet

Publications and source records attributed to P Niaudet.

At least 19 recordsLinked to original sources
PubMed1998

Software and database for the analysis of mutations in the human WT1 gene.

The WT1 gene, located at 11p13, encodes a zinc finger transcription factor involved in renal and gonadal development and in Wilms' tumor. Constitutional mutations of this gene have been described in most patients with Denys Drash syndrome (mesangial sclerosis associated with male pseudohermaphrodism and/or Wilms' tumor), but also in patients with genitourinary abnormalities and Wilms' tumor (WT) or presenting with only unilateral or bilateral WT. Moreover, approximately 10% of Wilms' tumors carry WT1 mutations at the somatic level. To facilitate the genotype-phenotype correlation analyses, we have created a software package along with a computerized database of germline (70 entries) and somatic (28 entries) mutations reported in the literature.

Computer Communication Networks↗
PubMed1998

Percutaneous transluminal angioplasty of renal artery stenosis in children.

Twenty percutaneous transluminal renal angioplasties were performed on 16 children (mean age 8.7 years) with hypertension secondary to renal artery stenosis (RAS). The aetiologies were neurofibromatosis (n = 1), Williams syndrome (n = 2), Takayasu arteritis (n = 1) and fibromuscular dysplasia (n = 12). The stenosis was isolated proximal or distal in 13 cases and multiple in 3 cases. Angioplasty resulted in a complete cure without medical treatment in 9 cases. Angioplasty allowed a reduction of medical treatment in two single stenoses, but was ineffective in all cases of multiple stenoses. Our findings show that angioplasty of RAS in children is an effective treatment when the stenosis is isolated, with a 69 % success rate. It seems ineffective in case of multiple stenoses (three cases).

Adolescent↗
PubMed1998

Renovascular hypertension and vascular anomalies in Alagille syndrome.

Alagille syndrome (AS) is characterized by the association of at least three of the following five abnormalities: chronic cholestasis, peripheral pulmonary artery stenosis, vertebral arch defects, embryotoxon, and typical facies. In addition to urological abnormalities, tubulointerstitial nephritis, renal tubular acidosis, and mesangiolipidosis have been noted in AS. The usual manifestations of such renal pathologies rarely include hypertension. We report five patients with at least four of the five major features of AS who developed secondary hypertension of renovascular origin 3.5-28 years after the initial diagnosis of AS. Angiography demonstrated uni- or bilateral renal artery stenosis and various other abnormalities of the main arteries in all five patients: aorta (3 cases), celiac artery (4 cases), superior mesenteric artery (1 case), subclavian artery (1 case). Our findings underscore the value of arterial blood pressure monitoring in patients with AS. If hypertension occurs, a renovascular origin should be sought. The diffuse vascular abnormalities which appeared to be a feature of AS in these patients should prompt larger studies of vascular abnormalities in AS.

Acidosis↗
PubMed1998

Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis.

Between 1980 and 1994, 38 children with severe forms of Schönlein-Henoch purpura glomerulonephritis were entered into a prospective study to evaluate methylprednisolone pulse therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and/or had 50% or more crescentic glomeruli. Initial renal biopsies were obtained from all patients and revealed diffuse proliferative endocapillary glomerulonephritis in 2, focal and segmental glomerulonephritis in 4, and endo- and extracapillary glomerulonephritis in 32, 21 of whom had 50% or more glomeruli with crescents. Patients were treated with intravenous pulse methylprednisolone (3 days) followed by oral prednisone (3.5 months). At the latest follow-up, 1-16 years after initiation of therapy, 27 children had clinically recovered, 3 showed minimal urinary abnormalities, 4 persistent nephropathy, and 4 had progressed to end-stage renal failure. Sequential renal biopsies were obtained from 30 patients, 7-25 months after initiation of therapy. The clinical outcome correlated well with of the activity (hypercellularity, cellular and fibrocellular crescents, and interstitial edema with mononuclear cell infiltrates) and the chronicity (fibrous crescents, glomerular sclerosis, tubular atrophy, and interstitial fibrosis) indexes of post-therapy biopsies. Of particular interest were the post-therapy biopsies of the 18 patients who clinically recovered. They showed a significant decrease of the activity index from 5.1+/-1.1 to 0.4+/-0.8 with a decrease or even a disappearance of IgA deposits, while the chronicity index remained low (0.4+/-0.8 compared with 1.4+/-1). Although uncontrolled, our study suggests that methylprednisolone pulse therapy is effective in those patients at risk of progression of their nephropathy, especially if started early during the course of the disease before the crescents become fibrous.

Adolescent↗
PubMed1998

Renal transplantation in children with augmentation cystoplasty: long-term results.

PURPOSE: We assessed the long-term results of renal transplantation in children with augmentation cystoplasty. MATERIALS AND METHODS: We retrospectively reviewed the complications and followup in 14 pediatric renal transplant recipients with augmentation cystoplasty. The etiology of bladder dysfunction included posterior urethral valves in 10 cases, neurogenic bladder in 3 and vesicoureteral reflux in 1. All transplants were cadaver donor kidneys. Mean patient age at transplantation was 12.1 years (range 5 to 18). Augmentation cystoplasty was performed before and after transplantation in 10 and 4 cases, respectively. Detubularized ileum was used in 5 cases, tubular ileum in 4, tubular sigmoid in 4 and stomach in 1. RESULTS: Of the 14 transplanted kidneys 10 (71%) were functioning at a mean followup of 80 months (range 12 to 151). Serum creatinine was less than 1.4 mg./dl. in 9 patients. Four grafts were lost to chronic rejection. The 5 and 10-year graft survival rates were 84 and 73%, respectively. Two patients with a functioning kidney died of causes unrelated to augmentation cystoplasty. Complications included symptomatic urinary infections in 4 patients, hyperchloremic metabolic acidosis in 2, nephrolithiasis in the allograft in 2 and the hematuria-dysuria syndrome in 1. All patients were continent. CONCLUSIONS: Augmentation cystoplasty is a safe and effective method of restoring lower urinary tract function in the pediatric renal transplant population with a small noncompliant bladder.

Adolescent↗
PubMed1998

Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain.

Gitelman syndrome (familial hypokalemia-hypomagnesemia syndrome) is an autosomal recessive inherited renal disorder characterized by defective tubular reabsorption of magnesium and potassium. In this study a group of 18 unrelated and 2 related Gitelman patients, collected from six different countries have been screened for mutations in the human thiazide-sensitive sodium-chloride cotransporter (SLC12A3) gene. Fourteen novel SLC12A3 mutations are presented along with six mutations described earlier, and three neutral polymorphisms. Among the tested patients are two who carry a total of three heterozygous SLC12A3 mutations. Two-thirds of the total number of mutant SLC12A3 alleles are amino acid substitutions. Most SLC12A3 gene mutations, 14 out of a total of 20, are localized at the intracellular carboxy-terminal domain of the NCCT protein. The pathogenicity of individual SLC12A3 mutations is based upon their predicted effect on SLC12A3 protein, and segregation in family members. Evolutionary conservation of substituted amino acid residues and their frequency in control chromosomes is presented. Identical mutations have been found in Gitelman families from different geographical origin, suggesting ancient mutations originating from a common ancestor. As yet, we have not found any evidence for a possible genotype-phenotype correlation.

Amino Acid Sequence↗
PubMed1998

Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database.

Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription factor involved in renal and gonadal development, are found in most patients with Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with pseudohermaphroditism and/or Wilms tumor (WT). Most mutations in DDS patients lie in exon 8 or exon 9, encoding zinc finger 2 or zinc finger 3, respectively, with a hot spot (R394W) in exon 9. We analyzed a series of 24 patients, 10 with isolated DMS (IDMS), 10 with DDS, and 4 with urogenital abnormalities and/or WT. We report WT1 heterozygous mutations in 16 patients, 4 of whom presented with IDMS. One male and two female IDMS patients with WT1 mutations underwent normal puberty. Two mutations associated with IDMS are different from those described in DDS patients. No WT1 mutations were detected in the six other IDMS patients, suggesting genetic heterogeneity of this disease. We analyzed genotype/phenotype correlations, on the basis of the constitution of a WT1 mutation database of 84 germ-line mutations, to compare the distribution and type of mutations, according to the different symptoms. This demonstrated (1) the association between mutations in exons 8 and 9 and DMS; (2) among patients with DMS, a higher frequency of exon 8 mutations among 46, XY patients with female phenotype than among 46,XY patients with sexual ambiguity or male phenotype; and (3) statistically significant evidence that mutations in exons 8 and 9 preferentially affect amino acids with different functions.

Amino Acid Sequence↗
PubMed1997

A controlled study of deflazacort in the treatment of idiopathic nephrotic syndrome.

Forty patients with steroid-dependent idiopathic nephrotic syndrome (INS), a mean follow-up of 5.5 years, and a mean number of relapses of ten were blindly assigned to either deflazacort (DFZ) (n = 20) or prednisone (PDN) (n = 20) according to a ratio of equivalence of DFZ/ PDN = 0.8. This treatment was given for 1 year. The number of relapses was significantly lower in patients receiving DFZ. After 1 year, 12 remained in remission with DFZ compared with 2 with PDN. Growth velocity was not different in the two groups. Bone mineral content, assessed by quantitative computed tomography of L1 L2 vertebrae, decreased after 1 year by 6% in the DFZ group versus 12% in the PDN group (NS). The mean body weight increase of +3.9 +/- 4.1 kg in the PDN group was higher than that of the DFZ group, +1.7 +/- 2.8 kg (P = 0.06). Cushingoid symptoms tended to be less after 12 months in the DFZ group. In conclusion, this study shows that DFZ was more effective than PDN in limiting relapses in steroid-dependent INS, and that cushingoid symptoms, weight gain, and decrease in bone mineral content tended to be less marked with this drug than with PDN.

Adolescent↗
PubMed1997

Donor splice-site mutations in WT1 are responsible for Frasier syndrome.

Frasier syndrome (FS) is a rare disease defined by male pseudo-hermaphroditism and progressive glomerulopathy. Patients present with normal female external genitalia, streak gonads and XY karyotype and frequently develop gonadoblastoma. Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by unspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. No case of Wilms' tumour has been reported, even in patients with extended follow-up. In contrast with FS patients, most individuals with Denys-Drash syndrome (DDS; refs 6,7) have ambiguous genitalia or a female phenotype, an XY karyotype and dysgenetic gonads. Renal symptoms are characterized by diffuse mesangial sclerosis, usually before the age of one year, and patients frequently develop Wilms' tumour. Mutations of the Wilms'-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS. WT1 is composed of ten exons and encodes a protein with four zinc-finger motifs and transcriptional and tumour-suppressor activities. Alternative splicing generates four isoforms: the fifth exon may or may not be present, and an alternative splice site in intron 9 allows the addition of three amino acids (KTS) between the third and fourth zinc fingers of WT1 (ref. 17). Here we demonstrate that FS is caused by mutations in the donor splice site in intron 9 of WT1, with the predicted loss of the +KTS isoform. Examination of WT1 transcripts indeed showed a diminution of the +KTS/-KTS isoform ratio in patients with FS.

Adult↗
PubMed1997

Long-term results of renal transplantation in children with the prune-belly syndrome.

PURPOSE: We assessed the long-term efficacy of renal transplantation in children with the prune-belly syndrome. MATERIALS AND METHODS: We retrospectively compared the outcomes of renal transplantation in 9 children with the prune-belly syndrome and 100 with malformative uropathy. RESULTS: Graft survival in the prune-belly syndrome and control groups was 50 and 72% at 5 years, and 50 and 47% at 10 years, respectively (not statistically significant). No statistically significant increase in serum creatinine was noted at 10 years in children with the prune-belly syndrome. Two patients with the prune-belly syndrome underwent internal urethrotomy after transplantation. All patients voided well and did not require intermittent catheterization. CONCLUSIONS: Renal transplantation in children with the prune-belly syndrome is not associated with a high rate of failure. However, these patients must be followed with regular urological evaluation since voiding efficiency may deteriorate.

Child↗
PubMed1997

Renal failure from mitochondrial cytopathies.

Mitochondrial cytopathies are metabolic diseases, expressing mutations in nuclear DNA, punctiform mutations or depletions in mitochondrial DNA. These genetic lesions alter mitochondrial oxidative phosphorylation, with a reduction in energy produced for cell activity. Renal disease may be the first sign of mitochondrial cytopathy, or it may appear together with neurological and neuromuscular signs. Fanconi's syndrome, a benign sign of renal tubulopathy, is particularly frequent in newborns with mitochondrial cytopathy, whereas tubulointerstitial nephropathy, which affects infants and adults, is more serious because it develops into terminal uremia. Findings of hyperlactatemia and reduced enzymatic activity on the respiratory chain in tissue biopsies are of diagnostic significance in mitochondrial cytopathy. A breakthrough is being made in our understanding of genetic alterations in mitochondrial DNA, and with future therapy, the kidney, a target organ, may be safeguarded.

Adult↗