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We performed a case-control study in children diagnosed by the first episode of upper urinary tract infection with or without vesicoureteral reflux to evaluate the association of functional polymorphism of interleukin-8 (-251AT and +2767AG), and its receptor CXCR1 (+2607GC).Genomic DNA was obtained from 265 children with a clinical and laboratory diagnosis of urinary tract infection who were recruited in northeast Italy. The children were subdivided as 173 who were dimercapto-succinic acid scan positive with positive static renal scintigraphy in acute conditions, consistent with the diagnosis of acute pyelonephritis, and 92 who were dimercapto-succinic acid scan negative. Genetic analysis for the same polymorphisms was also extended to a control population of 106 umbilical cord DNA samples.Statistical analysis of genotype data showed that 1) the tested populations were in Hardy-Weinberg equilibrium, 2) there were significant differences between the dimercapto-succinic acid scan positive and negative groups (p=0.049), and the dimercapto-succinic acid scan positive group vs controls (p=0.032) in terms of interleukin-8 -251AT polymorphism frequency, 3) there was also a significant difference in the distribution of IL-8 -251AT and +2767AG polymorphisms between dimercapto-succinic acid scan positive and negative children in the subgroup without vesicoureteral reflux (p=0.03 and 0.02, respectively) and 4) no significant differences were found in the frequency of the distribution of CXCR1 +2607GC polymorphism in all groups.These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux.

Summary Only few data are available on skin disorders in pediatric organ transplant recipients. In order to describe the whole range of dermatological diseases in a population of pediatric organ transplant recipients, we studied a group of 217 consecutive organ transplant recipients (168 kidney, 29 heart, 19 liver, one lung) aged

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.

The purpose of the study was to investigate the management of pyelonephritis in a large Italian pediatric population. A total of 1,333 patients (36% male) were considered. Escherichia coli was the most frequently isolated agent (89.9%), followed by Proteus mirabilis (3.6%) and Klebsiella oxytoca (2.1%). 27% of microorganisms were resistant to amoxicillin, 4% to amoxicillin/clavulanic acid, 11% to trimethoprim-sulfamethoxazole, 2.4% to gentamicin and less than 2% to ceftazidime. Despite this resistance pattern showing that oral antibiotics, such as amoxicillin/clavulanic acid, are effective in vitro as well as parenteral antimicrobials, a parenteral antibiotic was given initially to 756 (57.2%) children. A prophylactic regimen was started in 922 patients with a rate of reinfection during prophylaxis of 9.5%; a higher rate of reinfection was observed in patients with reflux (25%) compared to children without reflux (3%) (p < 0.0001). Vesicoureteral reflux was demonstrated in 30% of patients. The number of renal abnormalities detected by DMSA in patients with and without reflux was significantly different (p < 0.001). CRP was higher in patients with scars (p < 0.02). In conclusion, pyelonephritis represents a common disease with about 2,500 days of hospitalization per year in the Veneto Region where there is a pediatric population of about 800,000 under 15 years of age. The results of antimicrobial in vitro tests indicate that amoxillicin/clavulanic acid could represent the antibiotic of choice. The high frequency of malformations, observed even in children between 6 and 12 years of age, may suggest the need of an imaging study including DMSA scan and VCUG in all age groups.

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.

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.

Human cystatin C is a basic low molecular mass protein (13,359 Dalton) freely filtered through the glomerulus and almost completely re-absorbed and catabolized by proximal tubular cells. We measured serum cystatin C in 38 kidney transplant patients (23 males, 15 females) aged between 6 and 32 years. To assess renal function, serum and urinary creatinine were also determined in all patients, and creatinine clearance was finally calculated. Cystatin C was determined by a particle-enhanced turbidimetric assay, and creatinine was measured by gas chromatography-mass spectrometry. To compare the diagnostic efficiency of cystatin C with that of creatinine, inulin clearance was performed on 12 renal transplant patients, and receiver operating characteristic (ROC) analysis was applied. The results of this study demonstrate that serum cystatin C significantly increases in renal transplant patients with reduced creatinine clearance (70 mL/min per 1.73 m2) and that the diagnostic accuracy of serum cystatin C is better than of serum creatinine. Cystatin C may be utilized as a very marker of reduced GFR.

Renal calcification is a known complication of long-term furosemide therapy in infants with bronchopulmonary dysplasia (BPD). In a prospective study the clinical course and long-term renal sequelae of renal calcifications of 19 consecutive premature neonates (birthweight < 1250 g) with bronchopulmonary dysplasia who did not receive furosemide were examined. Infants were divided into two different groups on the basis of ultrasound evidence of renal calcifications (RC group) or absence of renal calcifications (NRC group). Serial examinations, performed at the age of 1, 2, 3, 6, 9 and 12 months, showed that 12 infants at the mean age of 68.5 +/- 12.8 days of life had renal calcifications (63%), and 3 of them had nephrolithiasis; 8 had bilateral renal calcifications. Among the 9 survivors, 2 had chronic renal calcifications at the age of 9 months; however, all normalized at the age of 12 months. Twelve infants received hydrochlorothiazide and spironolactone (63%), 17 had prolonged courses of xanthines and dexamethasone (89.5%), while furosemide was not part of the routine pharmacological administration. Statistical analysis showed that birthweight, gestational age, Apgar score and length of parenteral nutrition were comparable in the RC and NRC group infants. Mean serum creatinine, creatinine clearance, fractional sodium excretion and urinary calcium excretion values during the 12-month study period were comparable in the RC and NRC groups. Mechanical ventilation and hospital stay length were instead associated with renal calcification occurrence. The strongest indicator of renal calcification risk for this high-risk population is the severity of the unresolved acute lung disease, where different facets of respiratory management, other than the addition of furosemide, represent sufficient stimuli and renal injury to potentiate stone formation.

Coenzyme Q10 (CoQ10) deficiency has been associated with various clinical phenotypes, including an infantile multisystem disorder. The authors report a 33-month-old boy who presented with corticosteroid-resistant nephrotic syndrome in whom progressive encephalomyopathy later developed. CoQ10 was decreased both in muscle and in fibroblasts. Oral CoQ10 improved the neurologic picture but not the renal dysfunction.

sentant un syndrome de detresse respiratoire L'aginine-vasopressine (AVP), le peptide natriuretique auriculaire humain (hANP) et le bilan electrolytique du liquide corporeal ont ete etudies durant les cinq premiers jours de vie de onze enfants prematures (poids a la naissance) sous ventilation mecanique pour RDS. Les concentrations plasmatiques du hANP et urinaire de l'AVP ont ete determinees par radio-immunologie le premier, le troisieme et le cinquieme jour. Les taux d'arginine-vasopressine dans les urines sont restes constamment eleves pendant toute la periode d'etude (moyenne ± SD 13,5 ± 7,8 1 er jour, 12,0 ± 9,9 3 e jour, 13,2 ±.5,1 ng/l 5 e jour, p = ns), par contre le hANP plasmatique s'etait accru de facon significative au troisieme jour (626 ± 495 vs. 298 ± 240 pg/ml 1 er jour, p

SUMMARYFrom March to October 1993. 15 cases of haemolytic-uraemic syndrome (HUS) in children were detected in a large area of northern Italy, where only 8 cases had occurred in the previous 5 years. Analysis of stool and serum specimens obtained from 14 cases showed evidence of Verotoxin-producingEscherichia coli(VTEC) infection in 13. Serum antibodies to theE. coliO157 lipopolysaccharide (LPS) were found in 8 patients and to the O111 LPS in 2. An O86 VTEC was isolated from another patient. Fourteen children needed dialysis, and 1 died. No obvious epidemiologic link was observed among cases, most of whom lived in small townships. A case-control study did not show an association between HUS and food or exposure to cattle, but suggested an association with contact with chicken coops (OR = 6·5. 95% C.I. 1·2–34·9). However, VTEC were not isolated from stool samples obtained from the chicken coops involved. The risk factors for VTEC infection related to living in rural settlements, including the exposure to live poultry, should be considered in outbreak investigations.

A sensitive and accurate assay was developed for the measurement of 8-methoxypsoralen in plasma using electron-impact positive-ion mass fragmentography. 4,5,8-Trimethylpsoralen was used as an internal standard. Sample preparation consisted of a two-step liquid phase extraction using acetonitrile and methylene chloride. The calibration curve showed a linear relationship between the peak areas of 8-methoxypsoralen and 4,5,8-trimethylpsoralen over a wide range of 8-methoxypsoralen concentrations (1–500 ng/ml). Within- and between-run precisions, measured at five different drug concentrations, varied from 0.82 to 1.41% and from 0.82 to 1.86%, respectively.

Background. The incidence of donor kidneys with vascular anomalies ranges from 18% to 30%; such kidneys are usually at increased risk of vascular and urological complications. The aim of this study was to determine whether the use of cadaver kidneys with vascular anomalies would adversely affect posttransplant graft and patient outcome.Methods. From October 1987 to January 2004, 241 patients underwent kidney transplantation in our pediatric surgery department. Vascular anomalies were noted in 77/241 grafts (31.9%); 50 (64.9%) had multiple renal arteries and 22 (28.5%) venous anomalies. Patients were divided into three groups: Group A (1 renal artery and vein, 1 arterial and venous anastomosis [n = 161]), Group B (> 1 renal artery or vein, 1 arterial and venous anastomosis [n=33]), and Group C (> 1 renal artery or vein, > 1 arterial and venous anastomosis [n=47]). We compared the three groups for: patient and graft survival, incidence of posuransplant acute tubular necrosis, vascular and urological complications, postoperative mean creatinine levels, and posuransplantation hypertension.Results. We found no significant differences among the three groups regarding episodes of acute rejection or acute tubular necrosis. Creatinine levels reached normal levels within 30 days in all the groups without any significant differences. Furthermore, patient and graft survival were excellent (100% and 97%).Conclusions. The presence of vascular anomalies and their multiple or complex repair does not represent a theoretical disadvantage even in pediatric patients. In order to maximize the quantity and quality of donor kidneys especially in pediatric population, kidneys with vascular anomalies may be implanted with very little risk.

The anthropometry-bioimpedance analysis-nutrition (ABN) score is a recently proposed objective method of assessing malnutrition in children on chronic peritoneal dialysis (CPD) that uses nine parameters based on anthropometry, skinfold thickness and bioimpedance analysis. The aim of this prospective, cross-sectional study was to apply it to children treated with CPD in seven Italian paediatric nephrology centres, with a score of < 10.33 (the 3rd percentile in a population of 264 healthy children) classifying the children as malnourished. The other considered parameters were age, age at the start of dialysis and duration of dialysis; serum haemoglobin, urea, creatinine, total protein, albumin, transferrin, bicarbonate and C-reactive protein; residual urine output; urinary and peritoneal creatinine clearance; and daily protein and energy intake. The study enrolled 43 patients (mean age 10.2 +/- 4.2 years), 21 of whom (48.8%) had an ABN score of < 10.33: 15 with mild, five with moderate, and one with severe malnutrition. The malnourished patients started CPD at a younger age (P < 0.05) and had a longer duration of dialysis (P < 0.01), and a significant worsening in nutritional status was observed in those treated for more than 12 months of dialysis; they also had significantly lower serum albumin, creatinine and haemoglobin levels. In conclusion, protein-calorie malnutrition is common in children receiving CPD. A younger age at the start of dialysis and a longer duration of treatment are clear risk factors, and counterbalance the long-term viability of CPD in paediatric age.

Background. We report on a single-institutional experience with renal transplantation in patients with severe lower urinary tract dysfunction (LUTD) who underwent bladder augmentation or urinary diversion, and assess the long-term results. Methods. From September 1987 to January 2005, 255 patients (161 male and 94 female), 7 months to 39 years old of age (median age at time of transplantation 14 years), received 271 kidney transplants. Etiology of end-stage renal disease was LUTD in 83 cases. Among these patients, 24 had undergone bladder augmentation or urinary diversion. Results. We identified two groups of patients surgically treated due to LUTD: group 1 included 16 patients (eight male, eight female) aged 4 to 39 years (median 19 years) with bladder augmentation, whereas in group 2, seven patients (five male, two female) 7 months to 31 years old (median 17 years) with incontinent urinary diversion were reported. In the first group, surgical complications after kidney transplantation included one urinary fistula, one ureteral stenosis. Three patients of second group developed recurrent urinary tract infection. Cumulative graft survival rates of all patients transplanted was 69.4% after 15 years, whereas in the two investigated groups, group 1 and group 2, was 80.7% and 55.5% respectively (P=NS.). Conclusions. Drainage of transplanted kidneys into an augmented bladder or urinary diversion is an appropriate management strategy when the native bladder is unsuitable. Kidney transplantation in patients with bladder augmentation or urinary diversion for LUTD let achieve similar results to those obtained in the general population with normal lower urinary tracts.

The aims of our trial were to study the pharmacokinetics of tacrolimus in paediatric kidney transplant recipients. The study comprised 25 patients (median age 13 years, range 2-20 years) followed for 12 months; five pharmacokinetics profiles (within the first and second week and after 1 month, 6 months and 12 months) were obtained. Patients were divided into two groups: six children

This study was undertaken to determine the role of aquaporin 2 (AQP2) in the impaired urinary concentrating capacity observed in patients who underwent pyeloplasty because of congenital unilateral hydronephrosis as a result of pyeloureteral junction disease. Twelve children (mean age, 8 +/- 2 mo) were examined in the study. From day 1 to day 5 after surgery, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney used as internal control. After pyeloplasty, the postobstructed kidney was characterized by a reduced urinary excretion of AQP2 (approximately 54%) associated with polyuria that persisted from day 1 to day 5 (433 +/- 58 versus 310 +/- 74 ml/24 h at day 1; 326 +/- 44 versus 227 +/- 26 ml/24 h at day 5). In parallel, urine osmolality from the postobstructed kidney was significantly reduced compared with the contralateral kidney (111 +/- 12 versus 206 +/- 49 at day 1; 136 +/- 24 versus 235 +/- 65 mOsm/kg at day 5). Creatinine clearance from the postobstructed kidney was not significantly different compared with the contralateral kidney throughout the 4 d after surgery. However, on day 5, creatinine clearance from the postobstructed kidney became significantly lower. Prostaglandin E2 in the urine from postobstructed kidneys was found to be twofold higher than in the contralateral samples (26.0 +/- 6.7 versus 13.5 +/- 2.5 at day 5). It is concluded that (1) the selective downregulation of AQP2 in postobstructed kidney may account for the higher excretion of hypotonic urine, and (2) the local increase in prostaglandin E2 synthesis in postobstructed kidney may be involved in AQP2 downregulation and in maintaining a GFR similar to that of the contralateral kidney.

This paper summarizes the role of the Inter-Regional Reference Center (RC) of the North Italy Transplant program (NITp), in coordinating a donor procurement and organ transplantation network, with a special focus on the strategies to minimize immunological risk and complications after transplantation. In the NITp, patients enrolled on the renal transplantation (RT) waiting list are typed for HLA-A,B,DRB1 antigens with a genomic method. They are periodically screened for the presence of lymphocytotoxic antibodies in their serum by the RC and their suitability to receive the transplant is checked periodically. Cadaver kidney allocation is ruled by a computerized algorithm, named NITK3, established in 1997, which aims at ensuring quality, equity, transparency and traceability during all the phases of the allocation decision-making process. NITK3 has been set up by the NITp Working Group on the basis of biological, medical and administrative criteria and it is periodically reviewed after the analysis of transplant results. In this paper, we show the results of a preliminary analysis of RTs performed from 1998 to 2002 in nine out of sixteen centers of the NITp area, which demonstrates the general quality of the NITp program in terms of patients and graft survival and the special attention to the patients at higher immunological risk.

Plasma homocysteine, a new cardiovascular risk factor in both children and adults, is higher in chronic renal failure or kidney transplant patients. This alteration has been linked, in chronic renal failure, to plasma protein damage, represented by increased L-isoaspartyl residues. We measured plasma homocysteine levels and plasma protein damage in pediatric patients from four different Italian regions with conservatively treated renal failure; hemodialysis, continuous ambulatory peritoneal dialysis (CAPD), or transplants, to establish the presence of protein damage and the relative role of hyperhomocysteinemia.High performance liquid chromatography (HPLC) separation measured total plasma homocysteine levels, using precolumn derivatization with ammonium 7-fluorobenzo-2-oxa-1, 3-diazole-4-sulphonate (SBD-F). Plasma protein L-isoaspartyl residues were quantitated using human recombinant protein carboxyl methyl transferase (PCMT).In all patient groups, homocysteine levels were significantly higher with respect to the control (Control: 6.87 +/- 0.73 microM) conservatively treated, 14.19 +/- 1.73 microM; hemodialysis, 27.03 +/- 4.32 microM; CAPD, 22.38 +/- 3.73 microM; transplanted, 20.22 +/- 2.27 microM, p0.001 vs. control]. Plasma protein damage was significantly higher in conservatively treated, hemodialysis (HD) and CAPD patients, while in transplant patients it was no different from the control.We concluded that in pediatric patients of different Italian geographical origin, plasma homocysteine levels were significantly higher in all groups with respect to healthy children; therefore contributing to the elevated cardiovascular risk present in these patients. Plasma protein L-isoaspartyl content was higher in renal failure patients, but kidney transplant patients had normal levels, indicating that this kind of protein damage relates more to the toxic action of uremic retention solutes, than to plasma homocysteine levels.

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.

In this study we compared patient and technique survival of 163 new hemodialysis (HD) patients (age 11.4+/-3.1 years) and 295 peritoneal dialysis patients (7.7+/-4.8 years. P0.001), treated in 23 dialysis centers participating in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989-2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD patients. No statistically significant difference in patient survival between CPD and HD was found, while the survival of 102 CPD children younger than 5 years at the start of dialysis was lower ( P=0.0001) than that of 193 CPD and 160 HD patients aged 5-15 years. We registered 12 modality failures among HD (7.4%) patients and 44 among CPD (14.9%) patients. The main causes were vascular access failure and patient choice in HD, and infection in CPD patients. Technique survival was lower ( P=0.007) in CPD than in HD patients; a statistically significant difference ( P=0.01) was also observed between both the 0- to 5- and the 5- to 15-year-old CPD patients and the HD patients aged 5-15 years. Logistic regression analysis confirmed age at initiation of dialysis to be a predictor of patient death ( P=0.0001) in the whole patient population, and of technique failure in HD ( P=0.006) but not in CPD patients ( P=0.16).

PAX2, a homeotic gene of ‘paired box family’, is a nuclear transcription factor expressed in mesenchymal/epithelial conversion during the early stages of nephrogenesis; however, its repression is necessary for terminal differentiation of mature tubular cells. Transgenic overexpression in animal model causes epithelial hyperproliferation and microcyst formation. In humans, PAX2 expression has been observed in cystic and dysplasic tubular epithelia in kidney malformation and in kidney disease. We have investigated PAX2 expression and its colocalization with cytokeratin and/or vimentin in 17 biopsies of juvenile nephronophthisis (NPH), an autosomal-recessive renal disease characterized by diffuse renal fibrosis and occasional cysts. Fourteen cases were analyzed for deletion and mutation in the NPH1 gene locus and 33% resulted to be deleted or mutated; for the remaining cases the diagnosis was based on clinical and pathological criteria. The control group included 4 congenital dysplastic kidneys, and 10 biopsies of nephropathies with secondary chronic tubulointerstitial damage. In all cases of renal dysplasia a strong nuclear positivity was observed in immature tubules surrounded by αSMA-positive mesenchymal cells. In NI biopsies the tubular epithelia were almost PAX2 negative, although tubulointerstitial damage was severe. In 14/17 NPH1 moderate-to-strong nuclear PAX2 positivity of tubular cells was observed, particularly in cystic distal tubules located at the corticomedullary junction, but also in proximal tubular sections. The PAX2 signal co-localized more with cytokeratin staining than with vimentin. Our results confirm the observation of PAX2 expression in immature dysplastic tubules and its repression in mature renal tubular cells, also in the presence of severe secondary interstitial fibrosis. PAX2 seems to be overexpressed in NPH. The genetic defect of NPH, a disease probably due to a primary defect along the cascade of mesenchymal epithelial differentiation, could generate a functionally abnormal protein involved in focal adhesion signaling and cell/matrix interaction. The failure of PAX2 repression or its reactivation in NPH could be a marker of hyperproliferation and incomplete maturation of epithelial tubular cells, probably due to a defect cell/matrix cross-talk, and involved in interstitial fibrosis and cysts formation.

To evaluate the efficacy of renal transplantation in small pediatric patients, we have reviewed 41 allografts performed in 39 children (28 M/11 F) less than 6 years of age between 1987 and 1998 in the North Italy Transplant Program. Of these patients, 39 had a cadaver donor and 2 a living-related donor, with ages ranging from 20 days to 35 years. The mean follow-up was 56 months. Graft survival was 74.5% and 70.5% at 1 and 5 years, respectively. The causes of graft lost were acute rejection (4), graft vascular thrombosis (4), and hemolytic uremic syndrome recurrence (1). Only 1 patient has died due to chickenpox. Double and triple immunosuppressive therapies were used in 63% and 37% of patients, respectively, on the basis of different center protocols, without differences in graft survival. Steroids were successfully administered on alternate days in 37% of patients, 6-12 months after transplantation. Thrombosis was reported in 2 of 6 kidneys from donors less than 1 year of age and in 2 of 35 donors older than 1 year (P0.05). Thirty rejections occurred in 23 patients: 7 episodes were steroid resistant and were treated with ATG/OKT3. Thirty-four infections were reported in 16 of 41 patients; of these 17 were viral, 14 bacterial, and 3 due to Mycoplasma. Four surgical complications were reported: 1 graft artery stenosis, 1 ureteral stenosis, 1 urinary leak, and 1 lymphocele. Mean height standard deviation score improved from -2.0 +/- 1.3 pre transplantation to -1.8 +/- 1.4, -1.5 +/- 1.3, and -1.5 +/- 1.5 at 1, 2, and 5 years post transplantation. Linear growth was significantly better in infants treated with alternate-day steroids. Hypertension was a frequent complication, since 19 of the 30 patients with a 5-year follow-up were still being treated with antihypertensive drugs. In conclusion, graft survival in patients less than 6 years old is satisfactory and similar to that obtained in children aged from 6 to 18 years (70.5% vs. 78.9% at 5 years, P = NS). Consequently, since there are many difficulties in managing infants on maintenance dialysis, an early transplant should be considered. Donors older than 24 months carry a low risk of vascular thrombosis and may be successfully grafted in infants.

We report an 8-year-old girl who presented with hemolytic–uremic syndrome (HUS) as the onset manifestation of acute lymphocytic leukemia (ALL). The patient was admitted to the hospital for renal failure, thrombocytopenia, and anemia during a HUS outbreak. She was discharged 2 weeks later with normal renal function. One month later the girl presented with clinical and laboratory signs consistent with a diagnosis of ALL. The short time interval between HUS and ALL suggests that HUS was probably an early manifestation of acute leukemia.

The purpose of this study was to determine the frequency and the outcome of de novo malignancies in a cohort of renal transplant paediatric patients. The records of 493 kidney transplants, carried out in 454 paediatric recipients at the three paediatric transplant centres of the North Italy Transplant programme (NITp, Italy) were reviewed. 10 cases of malignancies (2.2%) comprising both PTLD (post-transplant lymphoproliferative disorders) (6 cases, 1.3%) and non-PTLD malignancies (4 cases, 0.88%) were reported. Non-PTLD included one urothelial carcinoma and one Wilms' tumour of the recipient's left native kidney, one abdominal dysgerminoma and one optic nerve glioma of the left eye. The PTLD consisted of localised or disseminated Epstein–Barr virus (EBV)—associated B-lymphocyte monoclonal (5 cases) and polyclonal (1 case) proliferations. All patients suffering from PTLD had been EBV-negative at the time of transplantion, but developed EBV primary infection after transplantion. All PTLD patient donors were EBV-positive. In addition, all but 1 patient received, before and/or after transplantation, a range of immunosuppressive drugs in addition to the baseline prophylactic immunosuppressive regimen. Moreover, 3 patients suffered from syndromes associated with a genetic predisposition to cancer. Finally, the malignancies reported here were associated with 20% graft failure and 20% mortality rates.

We report a simple and reliable high performance liquid chromatography method for measuring creatinine in serum and urine. The chromatographic run is performed on a C(18) column after protein precipitation with acetone and addition of cimetidine as an internal standard. The separation is carried out in 20 min at a flow rate of 0.8 ml/min, with a mobile phase consisting of 100 mmol/l sodium dihydrogen phosphate solution, containing 30 mmol/l sodium lauryl sulfate pH 3.0 and acetonitrile (60:36, v/v). The absorbance is monitored at 200 nm. The relationship between creatinine concentration and the creatinine/internal standard peak area is linear up to 1,088 micromol/l. Within-run precision measured at three different creatinine concentrations ranges from 0.89% to 2.34% in serum and from 0.34% to 1.10% in urine. Between-run precision varies from 1.68% to 3.17% in serum and from 1.58% to 1.85% in urine over a wide range of concentrations. Analytical recovery is between 98.71% and 101.25% in serum and between 98.96% and 100.27% in urine. The detection limit is 3.24 micromol/l for a signal-to-noise ratio of 3. The method shows a good linearity with the reference isotope dilution gas chromatography-mass spectrometry procedure (r=0.999), without interferences, even in the presence of high bilirubin concentrations.

We report a simple and rapid HPLC procedure for measuring p-aminohippuric acid in serum and urine. After deproteinization with acetonitrile and addition of p-aminobenzoic acid as an internal standard, the chromatographic run is performed on a C18 column with the absorbance detector set at 275 nm. The separation is carried out in 10 min at a flow-rate of 1.0 ml/min with a mobile phase composed of 7 mmol/l 1-decanesulfonic acid, pH 3.70, and acetonitrile (82:18, v/v). The relationship between p-aminohippuric acid concentration and the p-aminohippuric acid/internal standard peak area is linear up to 100 microg/ml. Within-run precision measured at three different p-aminohippuric acid concentrations ranges from 1.73 to 1.98% in serum and from 0.72 to 1.32% in urine. Between-run precision varies from 1.80 to 4.06% in serum and from 1.05 to 2.66% in urine. Analytical recovery is between 98.26 and 99.44% in serum and from 99.57 to 100.45% in urine. The method is very simple, sensitive, and requires small volumes of sample for the assay (100 microl). Therefore, it could be a useful tool for the analysis of p-aminohippuric acid in the evaluation of renal plasma flow.

We report a new HPLC procedure for measuring inulin in plasma and urine. Samples after dilution are boiled in mild acidic conditions and then analyzed on a C18 column. Solvent system A is 3.2 mM HCl, pH 2.5, and B is acetonitrile-3.2 mM HCl (60:40, v/v), pH 2.5. The separation is carried out in 8 min with a flow-rate of 1.0 ml/min and the absorbance monitored at 280 nm. The relationship between inulin and the recorded peak area is linear from 0.2 to 3.2 mg/ml with a correlation coefficient of 0.999 for plasma and 0.999 for urine. Within-run precision, measured at three inulin concentrations, ranged from 0.9 to 1.7% in plasma and from 0.8 to 1.2% in urine. Between-run precision varied in plasma from 2.7 to 3.2% and in urine from 3.0 to 3.3%. Analytical recovery ranged from 102 to 107% in plasma and from 101 to 105% in urine, respectively. The method is sensitive, selective and only 30-microliters samples are required. Therefore, it could be used to evaluate the glomerular filtration rate even in small babies and to perform studies in animals.

OBJECTIVE To compare the efficacy (maintenance of remission), safety and tolerability of cyclosporin (CsA) with those of cyclophosphamide in patients with steroid-dependent or frequently relapsing nephrotic syndrome (NS). DESIGN Open, prospective, randomized, multicentre, controlled study for parallel groups, stratified for adults and children. The setting was in nephrological departments in Italy. SUBJECTS AND INTERVENTIONS Seventy-three patients with steroid-sensitive idiopathic NS admitted to the study were randomly assigned to cyclophosphamide (2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6 mg/kg/day in children) for 9 months, tapered off by 25% every month until complete discontinuation at month 12. Seven patients lost to follow up were not considered in the analysis. The remaining 66 patients were followed up for 3-24 months after randomization. MAIN OUTCOME MEASURES Relapse-free survival; number of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory investigations (kidney and liver functions, haematological parameters); incidence of adverse events. RESULTS At month 9, 26 of 35 CsA-treated patients were still in complete remission and a further five patients were in partial remission; 18 of 28 cyclophosphamide-treated patients were in complete remission, and one in partial remission (P = NS). No difference between adults and children was seen with either treatment. The risk of relapse was similar between frequent relapsers (19 of 22) and steroid-dependent patients (8 of 14) given CsA, and those given cyclophosphamide (5 of 15 and 6 of 15). The mean number of relapses per year and the mean dose of prednisone per year were significantly less (P < 0.001) in both groups for the experimental year than for the year before randomization. At 2 years, 25% of the patients given CsA (50% adults and 20% children) and 63% of those given cyclophosphamide (40% adults and 68% children) had not had any relapse of NS. Tolerance to the two drugs was generally good. The CsA-related side-effects were mild and disappeared after drug discontinuation. CONCLUSIONS This study shows that both treatments are effective and well tolerated; more patients given cyclophosphamide had stable remissions.

The results of the first 3 years' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986-1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. the incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.

A nonradioactive in situ hybridization technique was utilized for the rapid and early diagnosis of cytomegalovirus (CMV) infection in children undergoing kidney transplantation. The cellular samples were obtained directly from the organs thought to be affected on the basis of clinical findings: bronchoalveolar lavage during interstitial pneumonia (7 samples from 6 cases); fine-needle aspiration biopsy (FNAB) of the liver during acute hepatitis (1 case); kidney FNAB and peripheral blood where there was a greater than or equal to 25% creatinine rise with or without fever (26 episodes). Standard virus isolation procedures and an immunofluorescent technique on short-term cultures of human fibroblast cells were performed as a control. 6/23 children followed had a symptomatic CMV infection (4 had interstitial pneumonia; 1 had acute hepatitis, and there was 1 case of creatinine rise with fever). In all cases, the diagnosis was provided by in situ hybridization in less than 24 h. These results were confirmed 48 h later by immunofluorescence and after 5-25 days by standard viral cultures. In situ hybridization with a biotinylated probe proved to be a rapid and sensitive method for diagnosis of CMV disease, when performed on specimens obtained from the involved organs at an early stage of the infection. This diagnostic approach allowed a specific antiviral therapy to be undertaken promptly.

Neurophysiological studies have shown defects in peripheral conduction in up to 75% of adults with end-stage renal disease (ESRD), though abnormalities of central conduction seem more variable. There are no comparable pediatric data. We therefore measured median nerve somatosensory evoked potentials (SEPs) in 10 children with ESRD, maintained by hemodialysis, who had no neurological signs or symptoms, and compared the results with those for age-matched controls. The latencies of N9, P14, N20 and P22, and interpeak latencies, N9-N20, N9-P14 and P14-N20, were not significantly different between the two groups (Student's t test). However, the children with ESRD were significantly retarded in growth and when arm length was taken into account, a significant difference in peripheral conduction was revealed. There was no correlation with other indexes of disease severity (parathormone, aluminium, Hb, Na, K, Cl, BUN and creatinine). SEPs appear to reflect subclinical changes in peripheral conduction in sensory pathways in children with ESRD which are not correlated with other measures of disease severity.

The aim of this study was to evaluate the effect of correction of chronic anaemia on the physical performance and the cardiovascular response to effort in children with end-stage renal disease (ESRD) maintained by haemodialysis. Seven patients (mean age 13.9 years) underwent triangular-type treadmill exercise testing before [haemoglobin (Hb) 6.3 +/- 0.9 g/dl] and after (Hb 11.2 +/- 1.2 g/dl) anaemia correction with recombinant human erythropoietin (rHuEPO). After treatment, the work-load reached, the peak oxygen uptake and average ventilatory anaerobic threshold (VAT) values were significantly increased (P less than 0.01, P less than 0.001, P less than 0.05 respectively). VAT values, expressed as a percentage of normal values, increased from 55.7 +/- 16.6% to 82.4 +/- 21%. This improvement correlated well with the increase in Hb (r = 0.79). Oxygen pulse also increased significantly, when tested after anaemia correction. In conclusion, these data demonstrate that when the anaemia of children with ESRD is corrected with rHuEPO, there is a clear improvement in aerobic work capacity and effort tolerance.

Creatinine clearance and renal sodium excretion were measured consecutively in three groups of 12 premature infants (gestational age less than or equal to 35 weeks) whose mothers had received either steroids or aminophylline, or steroids and aminophylline before delivery. We found no significant differences for plasma and urine creatinine and its clearance in the groups considered. The steroid group presented urine osmolality and urine/plasma osmolality ratio significantly higher than among the other groups. Furthermore, urine potassium excretion increased, and urine sodium and sodium fractional excretion were reduced. Aminophylline exposure did not interfere with the hydrosaline equilibrium nor with renal function of the preterms at birth. Our results reconfirm that corticosteroid hormones play an important part in the fetal renal maturation process, inducing a precocious maturation of the tubular Na(+)-K+ ATPase enzymatic system, that is substantially unmodified by aminophylline exposure. However, due to the prolonged half-life of aminophylline in prematures, it seems reasonable to verify the coupling of tubular and glomerular functions also in the following days of life.

Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia.

To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis.Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial.28 paediatric units in north east Italy.502 children aged 1 month to7 years with clinical pyelonephritis.Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (37 degrees C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry.Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk -4%, 95% confidence interval -11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (-0.9 to 6.0); white cell count 9.8x10(9)/l (SD 3.5) v 9.5x10(9)/l (SD 3.1), mean difference 0.3 (-0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference -0.05% (-1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry.Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children.Clinical Trials NCT00161330 [ClinicalTrials.gov].

We investigated glomerular filtration rate and renal function reserve after the surgical relief of partial obstruction.We evaluated 4 boys and 1 girl 9 to 14 years old who underwent pyeloplasty because of unilateral ureteropelvic junction obstruction. Contralateral normal kidneys served as controls. The glomerular filtration rate (inulin clearance), and urinary excretion of prostaglandin E2, thromboxane B2 and endothelin were determined at baseline and after a meal of 4 gm./kg. cooked unsalted red meat on day 4 postoperatively. Tests were repeated the following day 1 hour after the oral administration of 20 mg./kg. aspirin, an inhibitor of prostaglandin E2 synthesis. Urine was collected separately through a bladder catheter and another catheter placed in the upper renal pelvis at surgery.Glomerular filtration rate at baseline was significantly greater in normal than in surgically treated kidneys (77.2 ml. per minute, range 60 to 98 versus 63.6, range 43 to 78, p = 0.04). Aspirin did not change baseline inulin clearance in normal kidneys but it significantly decreased the glomerular filtration rate in operated renal units (-4% versus -26.4%, p = 0.04). The concentration of all vasoactive compounds was not significantly different in the urine specimens of normal and operated kidneys. The administration of aspirin resulted in a significant decrease in mean urinary prostaglandin E2 excretion plus or minus standard error in operated but not in normal renal units (0.64+/-0.12 ng. per minute versus 0.27+/-0.06, p = 0.04). When expressed as mean versus baseline values, protein induced glomerular hyperfiltration seemed lower in operated than in contralateral intact kidneys (6.9% and 12.4%, respectively).In the immediate postoperative period previously obstructed kidneys maintain renal function via mechanisms that depend on the activation of prostaglandin, mimicking normal renal function. This effect is decreased by drugs that inhibit prostaglandin E2 production. Therefore, renal damage may be present when the glomerular filtration rate appears normal.

We report the clinical and morphological features of an unusual hepatorenal disorder in 2 patients. The main clinical features were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis, leading to renal death in early childhood. Renal histology showed interstitial fibrosis, tubular atrophy and dilatation, glomerular cysts in the cortex and periglomerular fibrosis; liver histology was characterized by portal fibrosis and bile duct abnormalities. Evaluating the 12 patients published in the literature, the long-term prognosis of the liver function appears bad, suggesting the possibility of a combined liver and kidney transplantation.

We characterized the lipid-lipoprotein abnormalities encountered in a series of 45 nonnephrotic uremic children with various degrees of chronic renal insufficiency. A mild hypertriglyceridemia associated with decreased serum high-density lipoprotein cholesterol levels was confirmed. The correlation between high-density lipoprotein cholesterol and creatinine clearance showed a power behavior with a marked decrease in high-density lipoprotein cholesterol below a creatinine clearance value of 40 ml/min/1.73 m2. A number of uremic children accumulate an abnormal population of very low-density lipoprotein particles in their plasma. On agarose gel electrophoresis these particles migrate as a slow moving pre-beta band and are clearly distinguished from the regular fast moving pre-beta very low-density lipoprotein band. This electrophoretic phenomenon has been called double pre-beta lipoproteinemia. The prevalence of double pre-beta lipoproteinemia increased significantly with the degree of impairment of renal function, reaching highest figures in patients on hemodialysis. Accordingly, the very low-density lipoprotein cholesterol/triglyceride ratio also was significantly increased. The double pre-beta lipoproteinemia phenomenon was not detected in any of the control, nonuremic subjects. The clinical importance of double pre-beta lipoproteinemia in uremic plasma is related to its possible atherogenic role.