[Show abstract][Hide abstract] ABSTRACT: The human kidney-specific chloride channels ClC-Ka (rodent ClC-K1) and ClC-Kb (rodent ClC-K2) are important determinants of renal function, participating to urine concentration and blood pressure regulation mechanisms. Here we tested the hypothesis that these chloride channels could represent new drug targets for inducing diuretic and antihypertensive effects.
To this purpose, the CLC-K blockers benzofuran derivatives MT-189 and RT-93 (10, 50, 100 mg/kg), were acutely administered by gavage in Wistar rats, and pharmacodynamic and pharmacokinetic parameters determined by functional, bioanalytical, biochemical and molecular biology assays.
Plasma concentration values for MT-189 and RT-93 were indicative of good bioavailability. Both MT-189 and RT-93 dose-dependently increased urine volume without affecting electrolyte balance. A comparable reduction of SBP was observed in rats after MT-189, RT-93 or furosemide administration. Benzofuran derivatives treatment did not affect kidney CLC-K mRNA level or inner medulla osmolality, whereas a significant vasopressin-independent down-regulation of aquaporin water channel type 2 was observed at protein and transcriptional levels. In rats treated with benzofuran derivatives, the observed polyuria was mainly water diuresis; this finding indirectly supports a cross-talk between chloride and water transport in nephron. Moreover, preliminary in-vitro evaluation of the drugs capability to cross the blood-inner ear barrier suggests that these compounds have a limited ability to induce potential auditory side effects.
CLC-K blockers may represent a new class of drugs for the treatment of conditions associated with expanded extracellular volume, with a hopeful high therapeutic potential for hypertensive patients carrying ClC-K gain-of-function polymorphisms.
Journal of Hypertension 11/2011; 30(1):153-67. · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We demonstrated down-regulation of epidermal growth factor (EGF) and up-regulation of monocyte chemotactic protein-1 (MCP-1) in the renal parenchyma in children who underwent pyeloplasty for ureteropelvic junction obstruction (UPJO). These findings were paralleled by urinary levels of EGF and MCP-1 before and after surgery. The aim of this study is to evaluate the urinary excretion of these cytokines and β2-microglobulin (β2M) in children with urine flow impairment at the ureteropelvic junction or who underwent pyeloplasty.
Seventy-six patients with UPJO and 30 normal children (CTRL) were enrolled in the study. The UPJO patients were divided into obstructive (12), functional (36), and operated (28). Epidermal growth factor, MCP-1, and β2M urinary levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine.
Urinary β2M and MCP-1 increased significantly in the UPJO groups compared with the CTRL and significantly improved in the operated group. The obstructive group displayed reduced EGF excretion compared with the CTRL group. The urinary (u)EGF/uMCP-1, and uEGF/uβ2M ratios significantly decreased in both untreated groups. In the operated group, these ratios improved significantly.
The present study substantiates the role of urinary EGF, MCP-1, and β2M as markers of tubulointerstitial damage in human obstructive nephropathy. Furthermore, it suggests that surgical intervention is effective in the management of children with UPJO.
Journal of Pediatric Surgery 03/2011; 46(3):530-6. · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: VUR in patients with a duplex system (DS) is often treated by open surgery. The aim of this study was to evaluate the efficacy of subureteric polydimethylsiloxane (Macroplastique(®)) injection (SMING) in the management of VUR in duplex and single (SS) renal systems.
Fifteen children (24 refluxing renal units) with VUR in DS underwent SMING. VUR was more frequent in the lower moiety. VUR was graded moderate/severe in 88% of renal units. There was a history of urinary tract infections in 40% of cases. The outcome for DS patients was compared with 44 children (60 refluxing renal units) with moderate/severe VUR in SS.
The VUR resolution/improvement rate was 88% in DS and 95% in SS patients. Ureteric reimplantation was required because of recurrent VUR in 13% and 7% of DS and SS groups, respectively. Transient ureteral obstruction was observed in 1/15 and 5/44 patients. Two required double-J ureteric stenting for 3 months.
SMING seems an effective treatment for VUR in both DS and SS patients, even in severe cases. The complication rate does not significantly differ between the two groups.
Journal of pediatric urology 10/2010; 7(5):516-9. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS.
We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS.
Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank chi(2) 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy.
Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome.
Clinical Journal of the American Society of Nephrology 04/2009; 4(6):1065-72. · 5.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CD2-associated protein (CD2AP) is a crucial protein for the slit-diaphragm assembly and function. In spite of the fact that CD2AP knockout causes nephrotic syndrome in mice and the heterozygous +/- mouse is prone to proteinuria, little is known about the relevance of this molecule in human renal pathology.
A total of 80 Italian patients with idiopathic nephrotic syndrome were enrolled and screened for changes in the CD2AP gene. A normal control group of 200 healthy donors was also studied. The coding region of the CD2AP gene was analysed by polymerase chain reaction, denaturing high-performance liquid chromatography and sequencing. Peripheral blood mononuclear cells from patients with CD2AP mutations and from healthy donors were isolated by the Ficoll-Hypaque gradient, and the CD2/CD2AP interaction was studied on T-lymphocytes by confocal laser scanning microscopy analysis. The expression levels of CD2AP, nephrin and podocin proteins were evaluated by indirect immunofluorescence on renal biopsies from a patient with p.delGlu525 mutation and from control subjects. Moreover, the effect of the p.K301M mutation on cell viability was evaluated by flow cytometry and annexin V/propidium iodide staining.
Three heterozygous mutations (c.904A>T; c.1120A>G; c.1573delAGA) producing respectively aminoacidic changes (p.K301M, p.T374A) or a deletion in functional domains (p.delGlu525) were found in three unrelated patients. One (p.K301M) produced a lysine to methionine change in the third interactive SH3 domain (position 301) and resulted in the defective CD2-CD2AP interaction and clustering; the other (c.1573delAGA) caused the deletion of the glutamic acid in position 525 in the COOH-terminal region of binding with nephrin and was associated with down-modulation of CD2AP, podocin and nephrin glomerular expression.
Our findings suggest that CD2AP mutations modify the interaction with CD2 in lymphocytes and alter the composition of the renal slit diaphragm.
[Show abstract][Hide abstract] ABSTRACT: Haemolytic uraemic syndrome (HUS) is a disorder characterized by thrombotic microangiopathy, which is caused in 'typical forms' by gastrointestinal infections with Escherichia Coli species that produce verotoxins. Several studies have identified negative prognostic factors of the disease, among which prolonged oliguria, neurological involvement and increased leukocytosis have been more consistently reported. We have hypothesized that the genetic background may also predispose to the development of typical forms of HUS and may influence the clinical course of the disease.
Fourteen polymorphisms, known to influence the coagulation pathway or the activity of the renin-angiotensin system, have been selected and studied in 150 Italian children with typical forms of HUS. Two hundred healthy Italian children were used as controls.
The risk of developing HUS was strongly associated with the platelet glycoprotein 1balpha 145M allele (OR 3.08; CI: 1.62-5.85) (P < 0.001). A significant association was also found with polymorphisms located in the adipocyte-derived leucine aminopeptidase and factor V genes. A longer duration of dialysis was moderately associated with increased leukocytosis and with the 807T allele of the platelet glycoprotein 1a gene. High white blood cell count was also strongly associated with the risk of long-term sequelae (OR 2.91, CI: 1.21-6.98) (P < 0.02), whereas the 1166C allele of the angiotensin II type 1 receptor had a significant protective effect (OR 0.28, CI: 0.09-0.83) (P < 0.02).
These results highlight the role of glycoprotein 1balpha in the physiopathology of typical forms of HUS and show that the genetic background plays a role in the susceptibility and severity of the disease.
[Show abstract][Hide abstract] ABSTRACT: In a longitudinal cohort study our aim was to evaluate the cytokine pattern of children affected by Henoch-Schonlein purpura (HSP) and to correlate this pattern to vascular endothelium damage and to nephropathy. The following parameters were monitored at the onset of the disease (T0) and after 6 months of follow-up (T1): clinical scores, serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), soluble IL-2 receptor (IL-2sRalpha), fibrinogen, von Willebrand factor antigen (vWf:Ag) and soluble thrombomodulin (TMD) levels. A total of 24 children (9 M, 15 F), affected by HSP, aged between 3-14 years (median 6 years), were enrolled into the study. IL-2 serum levels were significantly increased at the onset of the disease compared to control group and T1. The same pattern was observed for IL-2sRalpha and TNF-alpha. Fibrinogen and vWf:Ag concentrations were significantly higher at the onset of disease than t1 and in control group. TMD levels resulted constantly within the normal range. Concerning the analyzed parameters, no significant difference resulted to be in subjects with and without renal involvement (hematuria and/or proteinuria). Finally, raised serum TNF-alpha concentration, related to vascular endothelium damage as shown by increased vWf:Ag levels, occurred invariably in children affected by HSP both with and without renal involvement.
Immunopharmacology and Immunotoxicology 02/2008; 30(3):623-9. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermolysis bullosa (EB) consists of a group of dominant or recessive autosomal diseases characterised by skin and mucosa fragility. The lesions leave erosions and scars that, in turn, can cause stenosis of tracheal, oesophageal, and genitourinary tract mucosae. The significantly increased survival of EB patients has determined the onset of complications never observed before, including genitourinary disorders such as hydroureteronephrosis, recurrent urinary tract infections, renal amyloidosis, IgA nephropathy and post-infectious glomerulonephritis. A 6-year-old boy diagnosed with recessive dystrophic EB Hallopeau-Siemens type (RDEB-HS) was referred to our clinic because of microhaematuria that evolved into intra-infectious macrohaematuria. Renal biopsy revealed an increase in both extracellular matrix and mesangial cells, with a focal segmental glomerulosclerosis with severe chronic tubulointerstitial damage. Immunofluorescence showed IgA mesangium deposits. Five years later, he was started on haemodialysis, because of worsening renal function. This is a rare case of a child with EB who was successfully treated with haemodialysis. The pertinent literature has been reviewed.
[Show abstract][Hide abstract] ABSTRACT: Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammation of the kidney characterized by destruction and replacement of its parenchyma with granulomatous tissue. It is associated with both chronic urinary obstruction and urinary tract infection (UTI).
We studied two children with chronic ureteropelvic junction obstruction (UPJO) and recurrent UTI nephrectomized for poor kidney function. An intraoperative renal biopsy was taken to relate the presence of infiltrating monocytes plus tubular atrophy to tissue expression of monocyte chemotactic protein-1 (MCP-1) and epidermal growth factor (EGF). XGP was diagnosed by a pathologist in both cases.
MCP-1 expression was significantly higher in the two patients compared with the controls or patients with uncomplicated UPJO. It also correlated with the extent of monocyte infiltration, whereas EGF was only significantly downregulated when compared with the controls.
MCP-1 would seem to play a key role in the pathogenesis of XGP by mediating the recruitment of circulating monocytes or by cells resident in the interstitial space.
European Journal of Pediatric Surgery 11/2007; 17(5):365-9. · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report our experience of treating dilating vesico-ureteric reflux (VUR) in children, using an injectable form of polydimethylsiloxane (Macroplastique, MPQ; Uroplasty BV, Geleen, The Netherlands), as medical treatment for moderate or severe VUR is associated with a high proportion of persistence or development of new scars.
The study included 32 children (40 ureters) with VUR; 13 (32%) were grade III, 20 (50%) grade IV and seven (18%) grade V. They were treated over a period of 42 months, 66% for some form of bladder dysfunction and 38% had associated diseases. The main indications were VUR grade, recurrent urinary tract infection and progression of reflux nephropathy. MPQ was injected under general anaesthesia via an 11 F cystoscope, x 30 objective, with a 5 F working channel.
The mean (sd) follow-up was 28.5 (10.2) months; VUR resolved in 80% of patients and improved to minimal VUR in the remaining 20%. The resolution/improvement rate was 72% after the first injection, 97% after the second and 100% after the third. There were no significant complications.
The endoscopic implantation of MPQ always corrected VUR even though 68% of the cases were grade IV-V. It should become the treatment of choice for severe VUR.
BJU International 05/2006; 97(4):805-8. · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We verify the sodium fraction excretion rate (FE Na) and potassium fraction excretion (FE K) rates in monosymptomatic nocturnal enuresis. We also correlate FE Na and FE K to urinary osmolality, nocturnal polyuria and vasopressin in the same population.
A total of 438 children 6 to 15 years old (mean age 9.7) presenting with monosymptomatic nocturnal enuresis were recruited from different centers. Inclusion criteria were 3 or greater wet nights a week, no daytime incontinence and no treatment in the previous 2 months. Exclusion criteria were cardiopathy, endocrinopathy, psychiatric problems and urinary tract abnormalities. Micturition chart, diurnal (8 am to 8 pm) and nocturnal (8 pm to 8 am) urine collection, including separate diuresis volumes, (Na, K and Ca) electrolytes and osmolality were evaluated, as well as serum electrolytes, creatinine and nocturnal (4 am) vasopressin. Diurnal and nocturnal FE K and FE Na were calculated. ANOVA test, chi-square test, Student's t test and Pearson correlation test were used for statistical analysis.
: Nocturnal polyuria (diurnal to nocturnal diuresis ratio less than 1) was found in 273 children (62.3%, group 1 and nocturnal urine volumes were normal in 165 with enuresis (37.7%, group 2). Nocturnal FE Na was abnormal in 179 children (40.8%), including 118 in group 1 (43.2%) and 61 in group 2 (36.9%) (chi-square not significant). FE Na was also increased in nocturnal versus daytime diuresis (Student's t test p <0.001). In group 1 nocturnal FE Na correlated with nocturnal diuresis (Pearson correlation p = 0.003, r = +0.175), while daytime FE Na and nocturnal FE Na correlated with diurnal diuresis (Pearson correlation p = 0.001, r = +0.225 and Pearson correlation p = 0.001, r = +0.209, respectively). In group 2 nocturnal FE Na did not correlate with diuresis (Pearson correlation p = 0.103, r = +0.128) but correlated with vasopressin values (Pearson correlation p = 0.042, r = -0.205). Urine osmolality was reduced in 140 children (31.9%) and correlated with nocturnal diuresis (Pearson correlation p = 0.003, r = -0.321). Vasopressin was decreased in 332 children (75.8%, 62.6% in group 1 and 13.2% in group 2). No significant difference was found between sexes and age of enuretic subgroups.
Nocturnal FE Na correlates with nocturnal diuresis, whereas daytime FE Na does not. FE K in daytime and nighttime diuresis does not statistically differ in nocturnal polyuric and nonpolyuric enuretic groups. Osmolality correlates with nocturnal diuresis, and vasopressin at 4 am was lower in the nocturnal polyuric group. The hypothesis of a subset of enuretic patients presenting with nocturnal polyuria associated with high nocturnal natriuria and low vasopressin values has been confirmed.
The Journal of Urology 07/2004; 171(6 Pt 2):2567-70. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Desmopressin may not be effective for nocturnal enuresis associated with polyuria and hypercalciuria. Nighttime hypercalciuria in an enuretic population from 5 centers and its correlation with nighttime polyuria were verified.
A total of 450 enuretic patients (278 males, 172 females, mean age 9.7 years) were evaluated with 72-hour micturition charts, urinalysis, serum creatinine and osmolarity, diurnal and nocturnal electrolytes with fractional Na+ and K+ urinary excretion, and nocturnal (4 a.m.) plasma vasopressin. Creatinine electrolytes and osmolarity were measured in daytime (8 a.m. to 8 p.m.) and nighttime (8 p.m. to 8 a.m.) urine volumes. Patients were divided into group 1 with nocturnal polyuria and group 2 without nocturnal polyuria. Hypercalciuria was defined as urinary calcium-to-urinary creatinine ratio greater than 0.21. Statistic evaluation was performed using chi-square, Pearson correlation and ANOVA tests.
Nighttime polyuria was demonstrated in 292 bedwetters (65% group 1). Nocturnal hypercalciuria was present in 179 of the 450 children (39.7%), including 125 in group 1 (42.8%) and 54 in group 2 (34.2%), which was statistically significant (chi-square p = 0.008, Pearson correlation test r = 0.157). Daytime calciuria was not statistically modified in either group (group 1 p = 0.054, group 2 p = 0.56). Adrenocorticotropic hormone (ADH) was normal in 18.5% and low in 81.5% of enuretics with nocturnal hypercalciuria. ADH levels and nocturnal hypercalciuria significantly correlated (p = 0.003, r = 0.148). Conversely, the group 2 patients had normal ADH levels.
Nocturnal hypercalciuria has a pivotal role in nocturnal enuresis, as it is significantly associated with low ADH levels and nocturnal polyuria. A new classification of nocturnal enuresis subtypes based on nighttime calciuria levels is mandatory to address treatment properly.
The Journal of Urology 11/2003; 170(4 Pt 2):1670-3. · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we analyzed the effect of a therapeutic intervention in 46 enuretic children, 26 (57%) of whom were hypercalciuric. All the patients (n = 46) were treated with DDAVP for 3-6 mo. The hypercalciuric patients (n = 26) received a low-calcium diet (approximately 500 mg/day) for the same period. After the therapy, the bed-wetting episodes stopped in 80% of the 46 patients tested. In those patients having low-AVP levels before the therapy, circulating AVP concentration returned to normal (>4 pg/ml), and the hypercalciuria was resolved in the hypercalciuric patients (calcium/creatinine ratio <0.2). Urinary aquaporin-2 (AQP2) levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day vs. the night urine samples (day/night AQP2 ratio). In the hypercalciuric patients, the day/night AQP2 ratio returned to values close to those found in the healthy children (from 1.19 +/- 0.20 before to 0.69 +/- 0.10 after the treatment, n = 26, P = 0.03). In contrast, in the normocalciuric children we saw no significant modulation of AQP2 excretion (from 1.07 +/- 0.14 before to 0.99 +/- 0.14 after the treatment, n = 20). This study clearly demonstrates that urinary calcium levels modulate AQP2 excretion and is likely to be useful for treatment of children with enuresis.
American journal of physiology. Renal physiology 11/2002; 283(5):F895-903. · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cystinuria is a heritable disorder of amino acid transport characterized by the defective transport of cystine and the dibasic amino acids through the brush border epithelial cells of the renal tubule and intestine tract. Three types of cystinuria (I, II, and III) have been described based on the urinary excretion of cystine and dibasic amino acids in obligate heterozygotes. The SLC3A1 gene coding for an amino acid transporter named rBAT is responsible for type I cystinuria, whereas the SLC7A9 gene coding for a subunit (b0,+AT) of rBAT is involved in determining non-type I (types II and III) cystinuria.
The SLC3A1 gene sequence was investigated in a sample of seven type I/type I, three type I/non-type I, six type I/untyped, and four untyped unrelated cystinuric patients by RNA single-strand conformation polymorphism (RNA-SSCP).
Eight new point mutations (S168X, 765+1G>T, 766-2A>G, R452Q, Y461X, S547W, L564F, and C673W) and seven previously reported mutations were detected. These new mutations increase the number of mutated alleles so far characterized in SLC3A1 to 62.
We have found SLC3A1 mutations in 0.739 of the type I chromosomes studied. The relatively high proportion of uncharacterized type I chromosomes suggests either that there may be mutations not yet found in SLC3A1 or that many of the assigned type I chromosomes in mixed type I/non-type I patients may have mutations in SLC7A9. If the hypothesis is excluded in the future, we believe that a third gene may be involved in cystinuria.
Kidney International 04/2001; 59(4):1250-6. · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study examined the hypothesis that nocturnal enuresis might be paralleled by aquaporin 2 (AQP2) urinary excretion. Eighty children who experienced nocturnal enuresis were studied and compared with 9 healthy children. The 24-h urine samples were divided into two portions: night collections and day collections. Creatinine equivalents of urine samples from each patient were analyzed by Western blotting. AQP2 levels were semiquantified by densitometric scanning and reported as a ratio between the intensity of the signal in the day urine sample versus the night urine sample (D/N AQP2 ratio). The D/N AQP2 ratio was 0.59 +/- 0.11 (n = 9) in healthy children and increased to 1.27 +/- 0.24 (n = 10) in a subpopulation of enuretic children who had low nocturnal vasopressin levels. In enuretic children who displayed hypercalciuria and had normal vasopressin levels, the D/N AQP2 ratio was 1.05 +/- 0.27 (n = 8). These data indicate that reduced secretion of vasopressin and absorptive hypercalciuria are independently associated with an approximately twofold increase in the urinary D/N AQP2 ratio. When low nocturnal vasopressin levels were associated with hypercalciuria, a nearly threefold increase in the D/N AQP2 ratio was observed (1. 67 +/- 0.41, n = 11). In addition, in all enuretic patients tested, the urinary D/N AQP2 ratio correlates perfectly with the severity of the disorder (nocturnal polyuria). The findings reported in this article indicate that urinary AQP2 correlates with the severity of enuresis in children.
Journal of the American Society of Nephrology 11/2000; 11(10):1873-81. · 9.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine the reference, bivariate, and tolerance intervals of the whole-body impedance vector in Italian children. This was a cross-sectional, multicenter study, and participants were chosen from the general school population. The impedance vector (standard, tetrapolar analysis at 50-kHz frequency) was measured in 3110 subjects, ages 2 to 15 y, and 2044 healthy children (1014 male and 1030 female) with weight and height within the 95th percentile were selected for the analysis (resistance-reactance graph method). The age-specific 95% confidence intervals of mean vectors and the 95%, 75%, and 50% tolerance intervals for individual vector measurements were plotted using resistance and reactance components standardized by the subject's height. Mean vectors from both sexes with separate 95% confidence ellipses were considered as representative of eight different age groups, from 2 to 13 y. There was a statistically significant sex effect on vector distribution from boys and girls in the age group of 14 to 15 y. The impedance vector distribution of children was also compared with healthy adult subjects (354 male and 372 female, age 15 to 85 y). There was a progressive, statistically significant vector shortening from age 2 to 15 y toward the adults' vector position. In conclusion, we established the trajectory followed by the mean impedance vector in children over ages 2 to 15 y and also obtained the reference, bivariate, and 95%, 75%, and 50% tolerance intervals of the impedance vector by age for healthy children, with which the vectors from children with altered body composition can be tested.