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Biomedical subjects

Alberto Edefonti

Publications and source records attributed to Alberto Edefonti.

At least 19 recordsLinked to original sources
PubMed2007

Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome.

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 (<or=2.0 standard deviation score in 6 patients) significantly increased (P < 0.05) at the end of follow-up in comparison to values at diagnosis. Nonpostural persistent proteinuria was present in 6 patients, and 4 patients had a glomerular filtration rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s). CONCLUSION: These data show that some patients with biallelic mutations in the chloride channel gene CLCNKB tend to present with pathological proteinuria and impaired kidney function after a median follow-up of 14 years, and growth retardation is common and sometimes related to growth hormone deficiency in these patients.

Adolescent↗
PubMed2006

Chronic peritoneal dialysis in children: catheter related complications. A single centre experience.

Despite advancements in catheter design and dialysis technique, catheter related complications still remain a common clinical problem in paediatric patients on chronic peritoneal dialysis (PD); in particular, infections are a common cause of patient's morbidity and technique failure. In the present paper, data on 89 catheters implanted between January 1986 and December 2002 are reviewed to analyse the major causes of complications and/or PD failure and to ascertain their optimal management. A total of 89 catheters were implanted in 78 patients at the start of chronic PD: 26 in children under 2 years of age, 14 in children aged 2-5 years and 49 in patients over 5 years. Mean age of patients was 76.1 +/- 73.0 months and median treatment time 14.5 +/- 13.1 months. All catheters were surgically implanted and partial omentectomy was performed in 70% of cases. Straight Tenckhoff catheters were used in 70 cases (78%), curled ones in 19 (22%). Sixty-three catheters (71%) had two cuffs, 26 (29%) a single cuff. The entry-site was the midline in 34 patients (38%) and the paramedian line in 55 patients (62%). Catheter survival rate was 80% at 12 months, 62% at 24 months and 58% at 36 and 48 months, respectively. The incidence of catheter-related complications was one episode every 6.4 PD-months, and they were mainly represented by peritonitis (61%), exit-site infections and tunnel infection (ESI + TI: 23%), catheter obstruction (5%), dislocation (3.5%), leakage (2.5%). After the introduction of curled single-cuff catheters, a considerable reduction in the peritonitis incidence was observed during the last 7 years. A more prolonged catheter survival was observed in older children (>5 vs. <2 years: P < 0.05). Leakage was less common in catheters with paramedian entry-site compared with catheters implanted on the midline. In 7 out of 11 (64%) patients with catheter obstruction, omentectomy had not been performed. Single-cuff catheters had a lower infection-rate than double-cuff catheter (P < 0.01). Single cuff-curled Tenckhoff catheter can be considered the first choice catheter. Single cuff-catheters are not associated with an increase of infections. The surgical technique requires a strict adherence to a standardized procedure and a dedicated team, in order to obtain a reduction of the complications, a prolonged catheter duration and a better quality of life.

Analysis of Variance↗
PubMed2006

A prospective multicentre study of the nutritional status in children on chronic peritoneal dialysis.

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.

Adolescent↗
PubMed2006

Shiga toxins present in the gut and in the polymorphonuclear leukocytes circulating in the blood of children with hemolytic-uremic syndrome.

Hemolytic-uremic syndrome, the main cause of acute renal failure in early childhood, is caused primarily by intestinal infections from some Escherichia coli strains that produce Shiga toxins. The toxins released in the gut are targeted to renal endothelium after binding to polymorphonuclear leukocytes. The presence of Shiga toxins in the feces and the circulating neutrophils of 20 children with hemolytic uremic syndrome was evaluated by the Vero cell cytotoxicity assay and flow cytometric analysis, respectively. The latter showed the presence of Shiga toxins on the polymorphonuclear leukocytes of 13 patients, 5 of whom had no other microbiologic or serologic evidence of infection by Shiga toxin-producing Escherichia coli. A positive relationship was observed between the amounts of Shiga toxins released in the intestinal lumen and those released in the bloodstream. The toxins were detectable on the neutrophils for a median period of 5 days after they were no longer detectable in stools. This investigation confirms that the immunodetection of Shiga toxins on neutrophils is a valuable tool for laboratory diagnosis of Shiga toxin-producing Escherichia coli infection in hemolytic-uremic syndrome and provides clues for further studies on the role of neutrophils in the pathogenesis of this syndrome.

Animals↗
PubMed2005

Successful medical treatment of multiple brain abscesses due to Nocardia farcinica in a paediatric renal transplant recipient.

Brain abscesses caused by Nocardia are rare, but it is very important to detect and treat them early because the associated mortality is 3 times higher than that associated with other bacterial brain abscesses. This infection is prevalent among adults on long-term immunosuppressive therapy; we report the case of a male kidney transplant recipient aged 12.7 years who developed early multiple Nocardia-induced brain abscesses that were successfully treated with linezolid, a novel antibiotic therapy.

Acetamides↗
PubMed2005

Pharmacokinetic of cyclosporine microemulsion in pediatric kidney recipients receiving A quadruple immunosuppressive regimen: the value of C2 blood levels.

BACKGROUND: The management of cyclosporine therapy in pediatric kidney-transplant recipients is largely based on single center's experience rather than on a univocal pharmacokinetic approach based on therapeutic drug monitoring. A prospective multicenter trial was designed to address the question whether C2 blood level monitoring of cyclosporine microemulsion therapy is feasible in the pediatric setting. METHODS: Sixty-four pediatric kidney-transplant recipients receiving a triple immunosuppressive regimen based on cyclosporine microemulsion had their cyclosporine dose adjusted to the same protocol-defined C2 targets from the time of the transplant until 2 years posttransplant. The interim analyses after 1 year of enrollment is presented in this study. RESULTS: One-year patient and graft survival were 100% and 94.8%, respectively. One-year rejection rate was 15%. C2 management of cyclosporine did not affect graft function: 1-year serum creatinine and glomerular filtration rate were 1.3+/-1 mg/mL and 71.2+/-20 mL/min/1.73 m2, respectively. C2 was the best single-point predictor of the area under the concentration curve throughout the entire follow-up, with a mean coefficient of correlation of 0.97+/-0.01. CONCLUSIONS: C2 management of cyclosporine microemulsion therapy is effective and safe in pediatric kidney-transplant recipients given a combined immunosuppressive treatment.

Adolescent↗
PubMed2005

C0 or C2 driven cyclosporine monitoring in long-term pediatric kidney transplant recipients: is there any threat for chronic rejection development?

The clinical management of cyclosporine has evolved greatly during the last decade thanks to the use of pharmacokinetic (PK) studies which confirmed the dose relationship between drug exposure and its biological effects. Therefore, cyclosporine PK monitoring during the early phase of the post-transplant period became essential to avoid over or underexposure to the drug thus preventing the risk of nephrotoxicity or acute rejection episodes. More recently, a simple PK determination based on cyclosporine blood concentration measured 2 h after the morning dose, has proven to be very effective for monitoring cyclosporine exposure in the early postoperative period. In this paper, the authors present a set of PK profiles obtained from a stable, long-term pediatric kidney transplant population and correlate these parameters with the risk of chronic rejection development. The study shows how cyclosporine monitoring based on the sole trough level determination misled a correct therapeutic behavior, as revealed by the PK parameters that were constantly below the therapeutic threshold in a small patient cohort who eventually developed chronic rejection. The C2 determination should be considered as the gold standard for cyclosporine monitoring in long-term pediatric recipients.

Child↗
PubMed2005

One-year results of basiliximab induction and tacrolimus associated with sequential steroid and MMF treatment in pediatric kidney transplant recipient.

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 (<0.3 mg/kg/day) during the first 2 months after transplantation. The assessment of steroid withdrawal needs a longer follow-up.

Adolescent↗
PubMed2005

Simultaneous mutations in the CLCNKB and SLC12A3 genes in two siblings with phenotypic heterogeneity in classic Bartter syndrome.

Two siblings (brother and sister) with renal tubular hypokalemic alkalosis underwent clinical, biochemical and molecular investigations. Although the biochemical findings were similar (including hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normal blood pressure), the clinical findings were different: the boy, who also presented syndromic signs, developed glomerular proteinuria and renal biopsy revealed focal segmental glomerular sclerosis; the girl showed the typical signs of classic Bartter syndrome. As described in a previous paper, a heterozygous mutation (frameshift 2534delT) was demonstrated in the gene encoding the thiazide-sensitive NaCl co-transporter (SLC12A3) of the distal convoluted tubule; the second molecular analysis revealed a compound heterozygous mutation (A61D/V149E) in the CLCNKB chloride channel gene in both subjects, inherited in trans from the parents. The children were finally diagnosed as having classic Bartter syndrome. These cases represent the first report of the simultaneous presence of heterozygous and compound heterozygous mutations in the SLC12A3 and CLCNKB genes, both of which are involved in renal salt losing tubulopathies, and confirm previous observations regarding classic Bartter syndrome phenotype variability in the same kindred.

Adult↗
PubMed2004

BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991].

BACKGROUND: Peritoneal dialysis (PD) is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs) and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. METHODS/DESIGN: The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the bicarbonate-buffered Bicavera solution for a period of 10 months. Patients will be monitored by monthly physical and laboratory examinations. Peritoneal equilibration tests, 24-h dialysate and urine collections will be performed 4 times. Peritoneal biopsies will be obtained on occasion of intraabdominal surgery. Changes in small solute transport rates, markers of peritoneal tissue turnover in the effluent, acid-base status and peritonitis rates and severity will be analyzed.

Adolescent↗
PubMed2004

Cardiac work up in primary renal hypokalaemia-hypomagnesaemia (Gitelman syndrome).

BACKGROUND: Potassium and magnesium depletion prolongs the duration of the action potential of the cardiomyocyte, which predisposes to ventricular arrhythmias. In addition, potassium or magnesium depletion might impair cardiac performance and facilitate coronary artery thrombosis. METHODS: Continuous 24-h ambulatory electrocardiographic monitoring, treadmill exercise testing and echocardiography were assessed in 21 patients (11 female and 10 male subjects, aged 5.9-39, median 19 years) with primary renal hypokalaemia-hypomagnesaemia. RESULTS: The QT interval corrected for heart rate was normal (between 379 and 430 ms) in 10 and slightly to moderately prolonged in the remaining 11 patients (between 446 and 509 ms). Plasma potassium, magnesium and bicarbonate were similar in patients with normal and in those with prolonged QT interval. Continuous ambulatory electrocardiography over 24 h and exercise testing did not detect significant abnormalities of cardiac rhythm or features suggestive of myocardial ischaemia. Finally, echocardiographic and Doppler assessment failed to reveal any abnormalities in myocardial morphology and function. CONCLUSION: The QT interval is often prolonged in primary renal hypokalaemia-hypomagnesaemia, confirming that potassium and magnesium depletion tends to prolong the duration of the action potential of the cardiomyocyte. The results of continuous ambulatory electrocardiography, exercise testing and echocardiography are reassuring. Nonetheless, we assume that dangerous cardiac arrhythmias may occur in patients with very severe hypokalaemia, during medication with drugs that prolong the QT interval or in the context of short-term non-adherence to the recommended regimen of care.

Adolescent↗
PubMed2004

Catheter-related infections in children treated with hemodialysis.

Infectious complications of the central venous catheter (CVC) are a major source of morbidity among children treated with hemodialysis (HD), with catheter-related bloodstream infections (CRBSI) being the most important clinical manifestations. As only a few studies of children on HD have been published, the management of CVC-related infections in this population is mainly based on data derived from adults or occasionally from children not affected by end-stage renal disease (ESRD). The aim of this review is to discuss current knowledge concerning the epidemiology, prevention, and treatment of catheter-related infections in children on HD. Catheters impregnated with antibiotics/antiseptics, lock antibiotic prophylaxis, nasal mupirocin, and the application of ointments at the exit-site have all been proposed as means of reducing the risk of CVC infections, but their real efficacy in the pediatric population has not yet been demonstrated. Furthermore, it is not clear how long antibiotic therapy should be continued, and there is still debate as to whether the catheter has to be removed. We propose some practical guidelines for the management of CRBSI in children with percutaneously inserted and surgically implanted HD catheters, but a number of unresolved clinical issues still remain, which will require prospective clinical trials specifically performed in pediatric patients with ESRD.

Bacterial Infections↗
PubMed2003

A multicenter experience on patient and technique survival in children on chronic dialysis.

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. P< 0.001), 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).

Adolescent↗
PubMed2003

Risk factors for poor renal prognosis in children with hemolytic uremic syndrome.

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.

Adolescent↗
PubMed2003

Treatment data during pediatric home peritoneal teledialysis.

Peritoneal teledialysis (telePD) is a modem-based communication link between the patients' cyclers and a computer in the dialysis unit that allows the transmission and storage of a series of automated peritoneal dialysis (APD) treatment data. In order to evaluate the usefulness of telePD in quantifying the problems that may occur during pediatric APD, we retrospectively studied four patients with a median age of 14.1+/-1.8 years during their initial months of telePD. The selection criteria were potential non-compliance in two cases (patients 1 and 2) and catheter malposition or fibrin occlusion in two (patients 3 and 4). The patients were treated using a Fresenius PD Night Cycler with teledialysis software. Thirty consecutive treatments per patient in the 1st and 4th months were examined, and a series of treatment parameters was calculated. The percentage of treatments with alarms and the number of alarms per treatment were high in both the 1st and the 4th month, particularly in patients 3 and 4. The main causes of the alarms were tube kinking, catheter malfunction, fibrin occlusion, and failure of electrical power. The number of shortened treatments significantly decreased in the 4th month of telePD. One non-compliant family was identified during the 1st month of PD, but psychosocial support helped to decrease the number of shortened treatments due to non-compliance in the 4th month. During the 4th month of telePD, the dwell time/total treatment time ratio (which represents the time of contact between the peritoneum and dialysis fluid) increased as a result of technical interventions aimed at reducing the infusion plus drain time. In conclusion, telePD proved to be useful in detecting and solving the clinical and technical problems of APD.

Adolescent↗
PubMed2003

Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood.

BACKGROUND: The dihydropyridine calcium channel blocker amlodipine and the angiotensin II antagonist irbesartan effectively reduce blood pressure in hypertensive children. METHODS: Eligible for the open-label, randomized study were nephropathic children between 6.0 and 18 years of age with plasma creatinine <177 micromol/L, overt proteinuria, untreated arterial hypertension (systolic, 5 to 30 mm Hg; and diastolic, 1 to 15 mm Hg;>95th centile) and stable immunosuppressive treatment. The initial dose of amlodipine was 5 mg (body weight, 20 to 40 kg) and 10 mg (body weight,>40 kg), respectively, that of irbesartan, which was 75 mg (body weight, 20 to 40 kg) and 150 mg (body weight,>40 kg), respectively. The dosage was doubled if necessary. RESULTS: A total of 26 children aged 6.1 to 17 years were allocated to receive either amlodipine (N = 13) or irbesartan (N = 13) for 16 weeks. Severe edema and headache occurred in two patients on amlodipine who withdrew from the study. No adverse experiences were noted in patients given irbesartan. Amlodipine [by 12 (10 to 14)/7 (5 to 10) mm Hg; median and interquartile range, respectively] and irbesartan [by 13 (9 to 16)/9 (7 to 11) mm Hg, respectively] reduced blood pressure (P < 0.01) in a similar fashion. Heart rate, plasma sodium, and creatinine did not change. Irbesartan slightly increased plasma potassium [by 0.1 (0.0 to 0.2) mmol/L; P < 0.05]. Plasma albumin and the urinary albumin/creatinine ratio were similar before and with amlodipine. On the contrary, irbesartan increased plasma albumin [by 4 (3 to 5) g/L; P < 0.03] and decreased the urinary albumin/creatinine ratio [by 242 (68 to 312) mg/mmol; P < 0.03]. CONCLUSION: The study demonstrates that in children the effect of angiotensin II antagonists on proteinuria is better than that of dihydropyridine calcium channel blockers.

Adolescent↗