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BACKGROUND: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (

Background: Ornithine transcarbamylase deficiency (OTC-D) is a urea cycle disorder caused by dysfunction of ornithine transcarbamylase, which frequently leads to hyperammonemia. Hyperammonemia represents a medical emergency requiring prompt treatment to reduce plasma ammonia levels and prevent severe neurological damage, coma, and death, particularly in patients with acute decompensation-related coma. The clinical symptoms of OTC-D can manifest themselves either at an early stage, which is often associated with severe symptoms, or in later life (late-onset OTC-D), when symptoms may be less severe. There is currently little agreement over diagnostic signs of the condition or the most appropriate therapeutic approach. Hyperammonemia is usually treated with ammonia scavengers, continuous venovenous hemodialysis, and dietary changes. N-carbamylglutamate is approved for the treatment of hyperammonemia in N-acetylglutamate synthetase deficiency and may have efficacy in other urea cycle disorders., Methods/results: Here, we report a 13-year-old girl who was diagnosed with OTC-D at the age of 3 years. On this occasion, the patient presented with vomiting, lethargy, and mental confusion. Despite biochemical parameters being within normal ranges, she was comatose within a few hours. She was promptly treated with a combined therapy of continuous venovenous hemodialysis and N-carbamylglutamate, resulting in a gradual normalization of clinical symptoms within 30 hours. No neurological damage was apparent at 18 months after treatment., Conclusions: This case demonstrates that clinical benefits can be obtained by beginning aggressive treatment of OTC-D within a few hours of the onset of severe neurological symptoms even in the absence of altered biochemical markers.

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Apheresis procedures are used in children to treat an increasing number of conditions by removing different types of substances from the bloodstream. In a previous study we evaluated the first results of our experience in children, emphasizing the solutions adopted to overcome technical difficulties and to adapt adult apheresis procedures to a pediatric population. The aim of the present study is to present data on a larger number of patients in whom apheresis was the main treatment. Ninety-three children (50 m, 43 f) affected by renal and/or extrarenal diseases were included. They were treated with LDL apheresis, protein A immunoadsorption, or plasma exchange. Our therapeutic protocol was the same as described in the previous study. Renal diseases and immunological disorders remained the most common conditions requiring this therapeutic approach. However, hemolytic uremic syndrome (HUS) was no longer the most frequent renal condition to be treated, as apheresis is currently the first treatment option only in cases of atypical HUS. In this series we also treated small children, showing that low weight should no longer be considered a contraindication to apheresis procedures. The low rate of complications and the overall satisfactory clinical results with increasingly advanced technical procedures make a wider use of apheresis in children realistic in the years to come.

Purpose: An important challenge for a pediatric nephrologist is to achieve in children the innovations of current adult dialytic technology., Methods: Five children, mean age 14.1 +/- 1.5 yrs, mean weight 31.5 +/- 5.8 kg, mean dialytic age 32 +/- 20 months, were evaluated after a 6-month treatment with paired filtration dialysis (PFD). We used two capillary membranes: a 0.4 m 2 polysulfone hemofilter and a 0.8 m 2 cuprophan dialyzer. There was a reinfusion system (1540 +/- 150 mL/h) between these two filters. QD 500 mL/min and QB 230 +/- 10 mL/min. Ultrafiltration (UF) 2400 mL/h was planned for the hemofilter. At base-line and after 6 months of treatment, in addition, we evaluated routine clinical parameters, and other parameters such as beta2-microglobulin, dialytic adequacy (Kt/V) and nutritional status (dietetic diary). The data were analyzed using the Student's t-test for paired values., Results: Medium values of small molecules did not demonstrate meaningful variations after 6 months of treatment. The extraction percentage after each session was between 63% phosphorous and 76% for urea, but only 25% for convection. Instantaneous urea clearance after 60 min was 178 +/- 10 mL/min. Dialytic efficiency and nutritional intake were appropriated: Kt/V 1.66 +/- 0.2; PCRn 1.65 +/- 0.2; protein intake 2.2 +/- 0.5 g/kg/die; caloric balance 71.2 +/- 15 Kcal/kg/die; protein balance 0.53 +/- 0.4 g/kg/die; and azotic balance 85.8 +/- 74 mg/kg/die. We confirmed the good depuration capacity from the middle molecules with convective treatments: beta2-microglobulin extraction was 53%. Moreover, in children we found good clinical tolerance to PFD with modest interdialytic symptomatology: headache (8%), hypotension (6%), and cramps and vomiting (<2%). Increased priming of the extracorporeal circuit was not a significant technical problem. The cuprophan membrane has been subsequently replaced with the polysulfone membrane., Conclusions: We can assert that this technique can also be performed in the pediatric age with similar results as in the adult age: good depuration of the small and averages molecules, good clinical tolerance, and shortening the dialytic sessions.

Darbepoietin alfa (NESP) is a new long-acting erythropoietin, with a half-life 3 times longer than the old epoietins. In the present study, we evaluated the efficacy of NESP in a group of children on hemodialysis. Seven children, five male and two female, with a mean age of 11.5 +/- 3 years and a mean weight of 34.1 +/- 11 kg, were enrolled in the study. All had been treated for at least 6 months with epoietin alfa at a mean dose of 106 +/- 76 IU/kg 3 times/week i.v. They were then given NESP at a mean dose of 1.59 +/- 1.19 microg/kg once a week i.v., according to the suggested conversion index (weekly epoietin alfa dose/200=weekly NESP dose). Anemia was evaluated at the end of a dialysis session. This was especially important for children less compliant with water restriction. Serum ferritin and percentage transferrin saturation (TSAT) were also monitored, as were dialysis efficacy (Kt/V), blood pressure, and heparin requirements. Before starting the new treatment, all patients had an adequate mean hemoglobin (Hb) level (11.19 +/- 1.7 g/dl) and an adequate iron status (TSAT 24.2 +/- 11.5, serum ferritin 220 +/- 105 mg/dl). Five of the seven patients were also treated with intravenous ferric gluconate (10-20 mg/kg per week). Six children were on antihypertensive treatment. After the 1st month of treatment, we observed an excessive increase in Hb, 12.3 +/- 1.7 g/dl, (P<0.05), with severe hypertension in the youngest two patients (Hb>13 g/dl). A short discontinuation of the medication, followed by restarting at a decreased dosage, allowed us to continue with the treatment. At the 2nd month of follow-up, a mean plasma Hb level of 12.2 +/- 1.2 g/dl was observed, with a NESP mean dose of 0.79 +/- 0.4 microg/kg per week. Steady state was reached at 3 months, with a mean Hb of 11.8 +/- 1.4 g/dl and a mean NESP dose of 0.51 +/- 0.18 microg/kg per week (P<0.05). These results persisted at 6 months of follow-up; only one child had a persistent increase in platelet level (373,000 vs. 555,000). Dialysis efficiency and heparin requirements during dialysis did not change significantly. The high efficacy of NESP allowed a consistent reduction in dosage. The suggested conversion index does not appear to be correct for pediatric patients. Our experience suggests that in this population the correct dose could be 0.25-0.75 microg/kg per week. Hypertension was the only major side effect reported. The influence of NESP on platelet proliferation needs to be further investigated. The single weekly administration of NESP could be effective and beneficial for both patients and clinicians.

Background: Chronic disease represents a very critical experience for personal identity. This is far more true in adolescence when corporeal, emotional, relational and cognitive changes are taking place. The aim of the present study is to draw attention to the social and emotional balance and the psychosocial adaptation in a group of nephropathic adolescents and to formulate a suitable assistance program., Methods: We studied two adolescent groups, one group of nephropathics and one group of healthy individuals, by administering the MMPI (Minnesota Multiphasic Personality Inventory) personality test., Results: We found significant differences between the mean score of the two groups in the clinical scale for depression, hypochondria and hysteria (p < 0.5); in addition, we observed a statistically significant difference in the emotional balance indicators., Conclusions: Our experience suggests that nephropathic adolescents require global awareness of their psychological problems through the use of innovative assistance methods. A new strategy involving a more modern approach (i.e., educational camps) and specific psychosocial rehabilitation programs should be introduced to improve the quality of life.

Background: 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., Methods: 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)., Results: 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, p < 0.001 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., Conclusions: 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.

The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G., (Copyright 2002 Wiley-Liss, Inc.)

The almost 4-year long experience of the IRCCS--"Casa Sollievo della Sofferenza" hospital (FG, Italy) dealing with 165 nonpalpable breast lesions mammographically detected is herein presented. According to a protocol based on the previously as well as relatively recent described guidelines for the clinico-pathological management of such lesions, the authors underline the necessity of a strict cooperation between the radiologist, the surgeon and the pathologist. They also emphasize the perspectives derived from such a new impact, among which the most impressive is the handling and sampling of this relatively new type of material with lesions which only rarely are grossly palpable ("pseudononpalpable lesions"), whilst often they are truly non palpable being of minute sizes ("microlesions") and even grossly "invisible" ("quasi-normal fibrofatty tissue"). Of note as consequences derived from the strict adherence to this type of protocol which anyone should adhere to there are also a decrease of frozen section diagnoses, a global increase in the surgical pathology lab workload, the ban for taking away any tissue from the lesion or from the area of concern for special studies, the technical approach to the identification of microcalcifications when they are present, the new questions & answers concerning with the completeness and the adequacy of excision, the state of surgical margins of the excised specimens, and the possible existence of residual in situ or infiltrating disease. The results herein presented area in consonance with those from other institutions so confirming the high incidence both of borderline lesions and in situ malignancies (overall incidence around 28%) and of the early and minute invasive cancers (44%) usually of favourable histological types, among truly nonpalpable breast lesions.

In order to evaluate the bacterial and endotoxin contamination in the dialysis fluids of our pediatric center and the effectiveness of chlorine dioxide (CD) compared with a conventional method, (1) deionized water, (2) dialysate fluid, (3) basic concentrate, and (4) acid concentrate were tested in 4 dialysis machines. Monitor sterilization was made using CD in protocol A and sodium hypochlorite/acetic acid in protocol B. Once every 2 weeks the deionized water set of distribution was routinely disinfected with peracetic acid. Each protocol lasted 1 months and the samples were taken, under aseptic conditions, on the 15th, 22nd and 27th day. All samples, at all stages of the study, showed an endotoxin concentration below the limits recommended by the Canadian Standard Association. Fifty-nine out of 72 samples in A and 62 out of 72 samples in B showed a bacterial count within the range recommended by the Association for the Advancement of Medical Instrumentation. The data show that both protocols produced the same results. However, protocol A is to be preferred for its simultaneous disinfecting-cleaning and descaling activity which proves time-saving.

The use of ultrasound for the diagnosis of urologic neoplasms in simple and accurate. Nowadays nephrologists and urologists advocate the use of ultrasound and the procedure now plays a complementary role of the clinical examination. We present a retrospective study regarding our experience with ultrasonography in the diagnosis of urologic problems. In the period february 95-february 96 we performed 672 ultrasound examination on children ranging in age from 30 days to 16 years. All examinations were performed using a 3.5-5 MHz real time convex scanner. The patients were examined in the supine position for imaging of the bladder and in the prone position for imaging of the kidneys. We report 3 cases of neoplasm of the genito-urinary tract screened with the use of ultrasounds in a selected paediatric population.