Search

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.

Background: Posttransplant recurrence of focal segmental glomerulosclerosis (FSGS) occurs in a relevant proportion of FSGS patients and represents an important clinical emergency. It is taken as a proof of the existence of circulating permeability plasma factor(s) that are also putative effectors of original proteinuria in these patients. Familial forms of FSGS do not recur, but the discovery of numerous patients with sporadic FSGS and mutations of podocin (NPHS2, that is actually an inherited disease) who received a renal graft require a re-evaluation of the problem. Methods: To evaluate the incidence of posttransplant recurrence of FSGS in patients with NPHS2, the authors screened for podocin mutations in 53 patients with the clinical and pathologic stigmata of FSGS who had renal failure and who had undergone renal transplantation. Results. Twelve children were found to carry a homozygous (n9) or a heterozygous (n4) mutation of podocin and were classified, according to current criteria, as patients with inherited FSGS. In 5 patients of this group (38%), proteinuria recurred after renal graft and in 2, renal biopsy results showed recurrence of FSGS. Prerecurrence serum of 3 patients of this cohort was tested for antipodocin antibodies with indirect immuno-Western utilizing human podocyte extracts and were found negative. The rate of FSGS recurrence was comparable in non-NPHS2-FSGS children (12 of 27) and adults (3 of 13). Also clinical outcome of recurrence and response to plasmapheresis and immunosuppressors were comparable, suggesting a common mechanism. Conclusion: These data show a high rate of FSGS recurrence in patients with NPHS2 mutations that is comparable with idiopathic FSGS and describe the successful therapeutic approach. Recurrence of an apparently inherited disease should stimulate a critical review of the mechanisms of recurrence and of original proteinuria in these cases.

We report a new high-performance liquid chromatography method developed for measuring inulin in plasma and urine using ion moderated partition chromatography and evaporative light-scattering detection. Samples are deproteinized with a zinc acetate and phosphotungstic acid solution and added with melezitose as an internal standard. The chromatographic separation is carried out in 16 min at a flow-rate of 0.6 ml/min using deionized water as the mobile phase. Within-run precision, measured at four different concentrations (0.050 mg/ml, 0.150 mg/ml, 0.300 mg/ml and 1.200 mg/ml), ranges from 1.7 to 3.4% in plasma and from 1.5 to 3.5% in urine. Similarly, between-run precision is in plasma from 2.0 to 4.3% and in urine from 2.0 to 4.4%. Analytical recovery ranges from 97.9 to 100.1% in plasma and from 99.1 to 99.7% in urine, respectively. Detection limit (signal-to-noise ratio=3) is 5 microg/ml both in plasma and urine. The method is simple, sensitive, without interference due to hexoses or drugs commonly taken by patients with renal diseases, and offers the advantage of measuring inulin without previous hydrolysis of the molecule.

GATA3 gene encodes a transcription factor expressed during thymus, liver, kidney, adrenal gland, central and peripheral nervous systems, placenta and T lymphocytes embryonic development. Mutations of GATA3 cause Hypoparathyroidism, sensorineural Deafness and Renal dysplasia syndrome (HDR). We report the case of a girl with a terminal deletion of the short arm of chromosome 10 (10p12.1-pter), including both HDR locus and the DiGeorge critical region 2 (DGCR2), with HDR phenotype but not DiGeorge syndrome 2 features. The girl developed chronic renal failure during the first year of life, associated with sensorineural hearing loss, facial dysmorphic features and psychomotor development. She had hypodysplastic kidneys and bilateral grade 3-vesicoureteric reflux. Her karyotype was 46,XX,del(10)(p12.1-pter). Quantitative analysis by Real Time PCR on blood DNA confirmed the lack of one copy of GATA3 gene. She underwent renal transplantation at the age of 11. Our patient is the first case with a large deletion of the short arm of chromosome 10 - that certainly involves DGCR2 - with the HDR phenotype but without the clinical features of DGS2. This peculiarity suggests the hypothesis that the mechanisms underlying this syndrome may be more complex. It is therefore possible that DGS2 may be determined by locus heterogeneity.

Tapeto-retinal degeneration is frequent in patients with nephronophthisis. Association of the most severe forms of tapeto- retinal dystrophy with NPH identifies a syndrome described first by Senior et al and Loken et al. This syndrome is distinct on molecular grounds from pure renal nephronophthisis (NPH1), which has its gene locus mapped on chromosome 2q13. We describe three families with large homozygous deletion of the NPH1 locus in which mild to moderate ocular lesions due to tapeto-retinal degeneration coexisted and were correlated to renal defects. This new association of NPH1 with retinal dystrophy is characterized by focal lesions of retina and is pauci- symptomatic in clinical presentation. For this reason it may remain unrecognized in most NPH1 patients. (Am J Kidney Dis 1998 Dec;32(6):1059-62)

Purpose To report on about LUTS after renal transplant (RTx) in pre-RTx anuric patients without associated urological malformations. Material and Methods Transplanted patients were considered for study if they had been anuric before transplant for at least 6 months, had no urological cause for their renal failure, were neurologically normal, had at least 12 months of follow-up after transplant, and were older than 5 years at follow-up. LUTS were evaluated using a questionnaire adapted from previous scoring systems in order to assess storage and voiding symptoms, bowel habit, and possible effect of symptoms on the patient's quality of life. Results Fourteen patients fulfilled the inclusion criteria. Median age at RTx was 11 (5-21) years, median duration of anuria before RTx 24 (7-46) months, and median post-RTx follow-up 2.7 (1.9-10.2) years. Thirteen cases presented a normal daytime voiding rate (5 to 7 times a day). One case presented episodes of daytime wetting and 4 suffered of urgency. None of the patients complained of a weak stream or about the need for straining during micturition. Ten cases (71%) presented nicturia and 1 occasional episodes of enuresis, nicturia was unrelated to length of follow-up. Twelve cases had a normal bowel habit. Only 1 patient reported that the symptoms affected her quality of life. Conclusions Pre-RTx anuric patients without associated urological malformation can present long-term storage symptoms. Nicturia was present in 71% of our cases irrespective of the length of follow-up.

Introduction Chemokines play a key-role in leukocytes recruitment in the site of inflammation, through the interaction with trans-membrane receptors. Genes that codify these chemokines and their receptors may present polymorphisms, which influence the proteins' level of expression and/or function. We have recently described an increased susceptibility to the development of acute pyelonephritis in children with interleukin 8 –251A > T polymorphism, presenting the first episode of upper urinary tract infection. Functional polymorphism of RANTES chemokine and its receptor CCR5 have been also identified. Material and Methods We carried out an association study of RANTES-403 G > A and CCR5Δ32 in 273 children with the first episode of upper urinary tract infection (UTI). Control population was represented by 326 blood umbilical cord DNAs coming from the same geographic area. Results Statistical analysis showed that RANTES-403 G > A phenotypic frequencies in the UTI group significantly differed from those of the control population (p = 0,007). A significant difference persisted when the genotype AA + GA was compared with the GG one (p = 0,002). Furthermore, comparing the frequencies observed in acute dimercaptosuccinic acid scan (DMSA)-positive and DMSA-negative patient with those observed in controls, a significant difference did emerge (p = 0,023 and p = 0,008 respectively). In addition, RANTES-403 G > A polymorphism frequency was significantly different in patients with vesico-ureteric reflux compared with the control population (p = 0,020). No difference were observed in the genotype distribution of CCR5Δ32 polymorphism. Conclusions Our results show that RANTES-403GG genotype is associated with an increased susceptibility to upper urinary tract infection.