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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.

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.

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.

This longitudinal study assessed the influence of post-transplant clinical and therapeutic variables in 50 kidney transplant recipients aged 2-19 yr receiving a triple immunosuppressive regimen consisting of cyclosporine microemulsion (CsA), steroids and MMF (300-400 mg/m(2) body surface area twice daily), the full pharmacokinetic profile (10 points) of which was investigated on post-transplant days 6, 30, 180 and 360. Total plasma MPA was measured by Enzyme Multiplied Immunoassay Technique. CsA therapeutic drug monitoring (TDM) was performed via C2 blood monitoring, while MPA TDM via C0. MPA Cmax, tmax, AUC0-12 and AUC0-4 pharmacokinetic profile changed significantly during the first post-transplant year. C0 was a poor predictor of the total MPA exposure [as measured by the area under the concentration-time curve AUC)], while a truncated AUC was a good surrogate of the 12-h profile (r = 0.91; p < 0.001) Graft function and cyclosporine therapy influenced MPA pharmacokinetics, as shown by the univariate and multivariate analyses. We conclude that because after transplantation MPA exposure varied over time, a strict TDM is advisable in the pediatric population.

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.

We assess the effect of the prune-belly syndrome (PBS) on renal transplantation outcome. Six renal transplantations were performed in five boys affected by PBS (median age 5.8+/-2.1 years, median weight 13.6+/-2.4kg). Renal graft survival, graft function, lower urinary tract dysfunction, urinary tract infections (UTIs), associated complications and patients' survival after 1 and 5 years of follow-up were analysed. The rate for 1-5-year graft survival was 66.7% (mean serum creatinine 98-103 micromol/l). The surgical treatment of the documented bladder obstruction (two patients) and the severe abdominal wall deficit (one patient) led to a reduction of UTI: the patients maintained their native urinary tract and none received prophylactic antibiotics. The lack of abdominal wall musculature led to severe mechanical complication in one patient, but Monfort's abdominal wall reconstruction was able to restore the graft's function. The outcome of patients with PBS who undergo renal transplantation is good. Before the transplant, an accurate assessment of urinary tract anomalies and deficiency of the abdominal wall musculature is mandatory, to program the appropriate treatment and obtain a good long-term prognosis for the renal graft.

We report the 1-year results with a triple immunosuppressive regimen in pediatric recipients of a first kidney transplant, in order to evaluate its safety and efficacy in the prevention of acute rejection and in the reduction of steroid side effects. The immunosuppression is as follows: (i) basiliximab (20 mg if body weight >30 kg; 10 mg if < 30 kg) is given pretransplant and at day 4; (ii) tacrolimus (Tac) is administered in order to obtain blood trough levels of 10-20 and 5-10 ng/ml during and after the first 2 months post-transplant, respectively; (iii) steroids are tapered during the first 6 months and then replaced by mycophenolate mofetil (depending on previous rejection episodes, infection status and the result of a routine biopsy) at a dosage of 4-600 mg/m(2) body surface area. Fifty-three children (median age 13 years, range 2-20) have entered this protocol. One-year patient and kidney survival are 100% and 94% respectively. During the first year a total of nine rejections in seven patients (13% of the cohort study) occurred, all but one responsive to steroids. Renal function was satisfactory throughout the first year (mean CrCl was 63.8 +/- 18 and 60.9 +/- 15.5 ml/min/1.73 m(2) at 6 and 12 months respectively). Subclinical signs of rejection were absent in more than 80% of biopsies (grade I Banff) at 6 months (n = 47); at the 12th month biopsy (n = 42) score I was stable in 20 patients (16 after stopping steroids) and had worsened in eight biopsies (six after stopping steroids). Major complications were insulin-dependent diabetes in three (5.6%) children with the need of insulin for a mean of 3 months; transient hyperglycemia (11 patients), treated with a dietary regimen, symptomatic viral infections (in 11 patients: two parvovirus B19, three cytomegalovirus and two Epstein-Barr virus systemic infections, three interstitial pneumonia, two BK nephritis). Tac doses more than 0.3-0.4 mg/kg/day are at significantly higher risk of viral infection. In conclusion, this immunosuppressive regimen is associated with a low percentage of clinical (13%) and subclinical rejections, but with a relatively high number of infections, prevented by a reduction in Tac doses (

There is some controversy about the safety of renal transplantation in patients with an augmentation cystoplasty because of the possibility of urinary tract infection in immunosuppressed patients leading to pyelonephritis and graft loss. Nevertheless, it is now well known that in patients with a small volume and poorly compliant bladder, reconstructive bladder surgery (augmentation cystoplasty or continent reservoir) creates a low-pressure and compliant reservoir, which protects the upper urinary tract and restores a functional lower urinary tract. Graft survival is not adversely affected when a kidney transplant is drained into a reconstructed bladder. When bowel segments are used for augmentation, a voiding modality with clean intermittent self-catheterization does not increase the risk of urinary tract infections, even in immunosuppressed patients.

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.

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.

A growing body of evidence identifies the renin-angiotensin system as a key factor in the onset and progression of renal damage in chronic partial obstruction, which often represents a complex diagnostic challenge. A prospective study was undertaken to evaluate the role of captopril mercaptoacetyltriglycine-3 (MAG-3) renography as an early diagnostic test of obstruction. We report the results in a subgroup of children who underwent surgical correction for pyeloureteral obstruction.Pyeloplasty was performed in 12 patients, including 10 males, 2 to 72 months old (median age 7) with unilateral hydronephrosis, including normal renal function and blood pressure. Basal and captopril enhanced diuretic renography with 99mtechnetium MAG-3 was performed within 24 hours using the same hydration and diuretic stimulus (0.75 mg./kg. furosemide), and 0.75 mg./kg. captopril was administered orally 60 to 90 minutes before scintigraphy.No adverse effects or modifications of the blood pressure were observed after captopril administration. The diuretic response was deeply worsened by angiotensin converting enzyme inhibition in each hydronephrotic kidney even when the basal study was only slightly abnormal (15-minute washout basal -27 +/- 16%, after captopril -9 +/- 13, p0.005). After surgical correction the diuretic washout during angiotensin inhibition appeared normal in all patients (15-minute washout -56 +/- 14%). Separate renal function and parenchymal transit of MAG-3 were not modified by angiotensin converting enzyme inhibition, preoperatively or postoperatively.Our data confirm the influence of angiotensin on the kidney excretory system in human hydronephrosis and suggest a role for captopril enhanced diuretic renography in the early diagnosis of pyeloureteral obstruction. Further work is needed to evaluate angiotensin converting enzyme inhibition as a protective agent in obstructive nephropathy.

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.

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.

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.

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.

Blind-ending bifid ureter in a girl with urinary tract infection, and a blind-ending duplicated ureter in her younger sister are described. The embryology of this rare anomaly is briefly reviewed.

We report 2 cases of cystinuria in which a nephrotic syndrome developed during treatment with alpha-mercaptopropionylglycine. This syndrome resolved after withdrawal of the drug and it did not recur when the alpha-mercaptopropionylglycine was given again in lower doses. The hypothesis is made that the nephrotic syndrome was dose-related. The alpha-mercaptopropionylglycine must be used in doses less than 50 mg./kg per day with regular monitoring of 24-hour urinary protein in cystinuric children.

In a retrospective, double-blind study, we analyzed, utilizing an immunohistochemical technique, the distribution of Endothelin (Et) in 20 renal biopsies of 17 children with nephrotic syndrome (NS): 9 cases of steroid-responsive and 8 of steroid-resistant minimal-change disease (MCD) and 3 cases of focal segmental glomerulosclerosis (FSGS). Thirteen out of 20 biopsies (9/9 steroid-responsive MCD and 4/8 steroid-resistant MCD) showed a weak positivity of the vascular endothelial cells, as the normal renal tissue samples obtained from tumor nephrectomies. Seven out of 20 biopsies, all steroid-resistant NS, showed a marked positivity of the vascular endothelium and of the tubules and/or interstitial cells. In 4 of these 7 cases (1 MCD, 3 FSGS) a positivity of glomeruli was also revealed. The positivity of vascular endothelium seems to confirm its central role in Et production. The marked immunoreactivity detected in the endothelial cells and other renal components reveals a local increase in Et in some steroid-resistant MCD and, particularly, in FSGS. These preliminary observations suggest that Et may participate (cause or epiphenomenon) in the mechanisms underlying the development of glomerulosclerosis and the progression of renal damage.

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and gammaGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.

Photopheresis (ECP) is a new form of photochemotherapy that induces a selective inhibition of the host response to foreign histocompatibility antigens and reverses allograft rejection after organ transplantation. This report describes four adolescent patients with recurrent rejection episodes after renal transplantation, all uncontrolled using standard protocols of immunosuppression (intravenous steroids and OKT3), yet successfully treated with a 6-mo course of ECP. The ECP treatment was performed at weekly intervals during the first month, at 2-wk intervals during the second and third months, and then monthly for another 3 mo. Creatinine clearance improved throughout the treatment in three patients and remained unchanged in one. All patients had a pre-ECP biopsy with a grade 2 or 3 rejection (Banff) with a diffuse infiltrate CD8, CD14, LFA-1 (166 cells positive/0.048 mm2), and VLA-4 (51 cells positive/0.048 mm2) positive, as well as a tubular expression of HLA-DR (6.2 sections of tubule positive/0.048 mm2), ICAM-1, and VCAM-1 (3.1 and 2.9 sections of tubule positive/0.048 mm2). A strong reduction of cell infiltrate and expression of LFA-1 (6.6 cells positive/0.048 mm2). VLA-4 (0.7 cells positive/0.048 mm2), HLA-DR (0.2 section of tubules positive/0.048 mm2), ICAM-1 (0.3 section of tubules positive/0.048 mm2), and a disappearance of VCAM-1 staining were observed in the biopsies performed after 3 mo of ECP. All patients remained rejection-free during ECP, without infections or other complications commonly observed with increasing doses of standard immunosuppression. The clinical improvement allowed a progressive reduction of oral steroids in three of the four patients treated.

The residual enzyme activity in tissues of a 6-year-old boy with myoglobinuria and carnitine palmitoyltransferase (CPT) deficiency was studied with malonyl-CoA, a specific inhibitor of CPT-I in rat tissues. In this patient the enzyme deficiency was limited to the CPT fraction insensitive to malonyl-CoA, since the residual activity was an increased amount of CPT sensitive to the inhibitor. CPT sensitivity to malonyl-CoA was also assayed in human liver mitochondria, and inhibition was similar to that found in rat liver. Moreover, comparative data on human liver mitochondria and biopsy specimens showed that, after freeze-thawing and homogenization, CPT sensitivity to malonyl-CoA was decreased in both these preparations, indicating that studies of CPT inhibition by malonyl-CoA in homogenates of frozen tissues may be equated to those in homogenates of frozen mitochondria.

Objective To analyze data on 503 chronic peritoneal dialysis (CPD) catheters implanted between 1986 and 2000 in pediatric patients enrolled in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (the Registry), comparing three different time periods: 1986 – 1990, 1991 – 1995, and 1996 – 2000. Design Retrospective study. Setting 23 dialysis centers participating in the Registry. Methods Data were collected from questionnaires filled in every year. The information for each peritoneal catheter included type, site and technique of insertion, exit-site orientation, exit-site care, complications, survival, and reason for removal. Patients 503 catheters were implanted in 363 pediatric patients aged younger than 15 years at the start of CPD: 97 catheters in patients under 2 years of age, 67 in patients aged 2 – 5 years, and 339 in patients over 5 years of age. Mean patient age at onset of CPD was 8.0 ± 5.1 years. All catheters were surgically implanted and omentectomy was performed in 82.4% of cases. The catheters used were Tenckhoff [468 (93.0%): 443 double cuff, 25 single cuff] and double-cuffed Valli [35 (7.0%)]. The entry site was in the midline in 153 cases (30.4%) and paramedian in 350 (69.6%). Results During 9048 dialysis-months we observed 451 catheter-related complications, yielding an incidence of 1 episode/20.1 CPD-months: 330 catheter infections (exit-site and/or tunnel infections), 26 leakages, 26 dislocations, 24 obstructions, 22 cuff extrusions, 6 hemoperitoneums, 17 others. 171 catheters were removed due to catheter-related causes; exit-site and/or tunnel infections were the main cause for removal (75.4%), followed by obstruction, dislocation, outer-cuff extrusion, and leakage. Younger children (< 2 years) had a higher risk of infectious causes of catheter removal compared to children aged 2 – 5 years ( p = 0.004) and over 5 years of age ( p = 0.002). During the 15-year observation period, a significant reduction in the incidence of leakage was observed and risk of leakage was lower in catheters with paramedian entry site compared to catheters with midline entry site. Removal and replacement of peritoneal catheters during the same surgical operation was performed in 76.3% of catheter removals. Catheter survival rate was 78.1% at 12 months, 58.5% at 24 months, 43.8% at 36 months, and 34.6% at 48 months. No difference in catheter survival was observed in younger children (< 2 years) compared with the two other age groups: < 2 years versus 2 – 5 years hazard ratio 0.7, 95% confidence interval (95%CI) 0.4 – 1.2; < 2 years versus > 5 years hazard ratio 0.8, 95%CI 0.5 – 1.1. Conclusions In this survey, we observed better catheter survival in comparison with data reported by the Registry in 1998. Catheter survival improved especially in younger children (< 2 years), a group that previously had a decreased catheter survival rate compared to older age groups. In addition to the progressive increase in experience acquired by dialysis centers, this upward trend may also be related to greater use of double-cuffed catheters, with paramedian exit site, and a higher frequency of omentectomy.

In chronic renal failure high serum urea levels (sUrea) are correlated with the onset of uremic symptoms. Urea has generally been considered relatively non-toxic, functioning more as a surrogate for other toxic solutes; however, it has been recently reported that it can contribute to uremic toxicity. Clinically sUrea are often difficult to interpret because of the wide range of kidney functions. To obtain a practical and easily accessible tool to evaluate sUrea, we have produced percentile curves for different ranges of chronic renal failure, defined with creatinine clearance ( C(Cr)) obtained with the Schwartz formula. Data were obtained from the Italian Pediatric Registry of Chronic Renal Failure (ItalKid); its inclusion criteria are: (1) C(Cr )75 ml/min per 1.73 m(2), (2) age20 years at time of registration, and (3) conservative treatment. To obtain the percentiles, the following patients were excluded: patients with an underlying disease, a concomitant treatment, or a disorder that could affect urea metabolism, per se, and/or food intake, and patients aged2 years. The study group included 690 subjects (mean age 9.56+/-4.54 years, 485 males). In total, 2,085 observations (C(Cr )and sUrea) were available for the construction of the percentile curves. A median of 258 (range 99-380) observations was obtained for each of the eight different categories of C(Cr )(intervals of 10 ml/min per 1.73 m(2)). The 10th, 25th, 50th, 75th, and 90th percentiles were calculated and a graph was produced. Patients with the highest urea percentiles showed significantly higher plasma levels of phosphorus and parathyroid hormone and significantly lower hemoglobin concentrations and bicarbonate levels. Our percentile curves may help to identify subjects with inappropriate sUrea for a given C(Cr).

Anemia, through a hyperkinetic state, is an Important contributor to myocardial function impairment. To determine the cardiovascular effects of recombinant human erythropoietin (rHuEPO) therapy, 10 chronic peritoneal dialysis (CPD)-treated anemic children were studied be fore and during 18 months of treatment. The following parameters were recorded: hemoglobin (Hb) [percent of target level (TL) = x 2 standard deviations of normal Hb values for age and sex], heart rate (HR, beats/minute), mean arterial pressure (MAP, mmHg), end-diastolic left ventricular diameter (EDLVD, mm/sm BSA), shortening fraction (SF, percent), and Interventricular septal thickness (IVS, mm/sm BSA). Student's t-test for paired data showed (vs time before treatment, TO) a progressive Increase In Hb, a progressive decrease In HR, and a progressive Increase In MAP. EDLVD progressively decreased, while SF and IVS remalned unchanged throughout the study. Regression analysis showed a close correlation between anemIa cor rection and decrease of HR (p Our data indicate that anemia correction In these patients Is mainly associated with a decrease in hyperkinetic state (HR reduction with SF unvaried), while left ventricular function and dimensions remain normal, despite an Increase in MAP.

Objective To report the complications and outcome of 10 newborns affected by acute renal failure (ARF), treated by continuous peritoneal dialysis (CPD). Design All newborns admitted for tertiary treatment to the Neonatal Intensive Care Unit of the University of Padova, who underwent CPD between February 1986 and December 1990, were analyzed retrospectively. Patients Ten newborns (mean weight 2077 g, range 540–4930 g) received CPD, 6 of whom were preterm. All the survivors completed the study. Interventions A number 9,5 French Tenckhoff catheter was used, and a closed circuit was created by means of a modified continuous ambulatory peritoneal dialysis (CAPD) technique. The mean duration of dialytic therapy was 7 days. Results At the end of the dialytic period, 7 of the 10 patients had normal serum potassium and sodium values. CPD produced two different types of complications: leakage of the dialytic fluid in very low weight newborns and one episode of peritonitis during a chronic dialysis treatment. Six died of severe respiratory failure (in no case, however, was this attributable to ARF or CPD procedure). All but one of the survivors regained normal renal function. The only exception necessitated a kidney trans plant. Conclusion We believe that this technique, although invasive, improves the outcome of both preterm and low birth weight newborns affected by ARF.