[Well-being in adulthood of patients with chronic conditions in childhood: The GEDEPAC-2 questionnaire]. / Bien-être à l'âge adulte des enfants atteints de maladies chroniques : le questionnaire GEDEPAC-2.

BACKGROUND: In France, chronic diseases affect 3 million children. In children with chronic conditions, long-term somatic outcome has been well described, but little is known about the psychosocial aspects of well-being. METHODS: Our aim was to build a self-administered questionnaire of global well-being in adults who had a chronic disease since or during childhood using a multidimensional and nonspecific approach. The questionnaire was constructed by a multidisciplinary group (epidemiologists, clinicians, sociologist, statistician). Items were built in compliance with reference data from the French general population (national surveys, free access) to allow comparative analysis adjusted for age and sex (and eventually other confounding factors) by indirect standardization (qualitative variables) or Z-scores (quantitative variables). RESULTS: The GEDEPAC-2 includes 108 items exploring 11 domains: education, employment, housing, material security, social links, civic engagement, leisure, environment, physical health/risky behavior, health-related quality of life and sex life. Factual questions and satisfaction scales jointly explore social well-being. Quality of life is analyzed in terms of physical quality of life, mental quality of life, fatigue and burden of treatment by 3 questionnaires validated in French (SF-12; MFI-20; Burden of Treatment Questionnaire). Experience of transition from pediatric to adult healthcare is described in 21 items. Paper and electronic versions were developed. CONCLUSION: Built in a multidimensional approach to well-being and in line with the available reference data, GEDEPAC-2 will facilitate the implementation of future studies on impact in adulthood of chronic disease in childhood.

Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).

Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome.

Atypical hemolytic and uremic syndrome (aHUS) is a severe disease strongly associated with genetic abnormalities in the complement alternative pathway. In renal posttransplantation, few data are available on recurrence risk and graft outcome according to genetic background in aHUS patients. The aim of this study was to identify risk factors for recurrence and transplant outcome and, in particular, the role of complement gene abnormalities. We retrospectively studied 57 aHUS patients who had received 71 renal transplants. A mutation in complement gene was identified in 39 (68%), in factor H (CFH), factor I (CFI), membrane cofactor-protein (MCP), C3 and factor B (CFB). At 5 years, death-censored graft survival was 51%. Disease recurrence was associated with graft loss (p = 0.001). Mutations in complement genes were associated with higher risk of recurrence (p = 0.009). Patients with CFH or gain of function (C3, CFB) mutations had a highest risk of recurrence. M-TOR inhibitor was associated with significant risk of recurrence (p = 0.043) but not calcineurin inhibitor immunosuppressive treatment (p = 0.29). Preemptive plasmatherapy was associated with a trend to decrease recurrence (p = 0.07). Our study highlights that characterization of complement genetic abnormalities predicts the risk of recurrence-related graft loss and paves the way for future genetically based individualized prophylactic therapeutic strategies.

Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation.

Eculizumab (anti-C5) has been sporadically reported as an efficient therapy for atypical hemolytic uremic syndrome (aHUS). However, the lack of series precludes any firm conclusion about the optimal use of anti-C5 for preventing or treating aHUS posttransplant aHUS recurrence. We thoroughly studied 22 renal transplant recipients with aHUS who received off-label therapy with anti-C5, including 12 cases, which have not been reported yet. Nine patients, all carrying a complement genetic abnormality associated with a high risk of aHUS recurrence, received prophylactic anti-C5 therapy to prevent posttransplant recurrence. Eight of them had a successful recurrence-free posttransplant course and achieved a satisfactory graft function, while the remaining patient experienced early arterial thrombosis of the graft. Thirteen renal transplant recipients were given anti-C5 for posttransplant aHUS recurrence. A complete reversal of aHUS activity was obtained in all of them. Importantly, the delay of anti-C5 initiation after the onset of the aHUS episode inversely correlated with the degree of renal function improvement. Three patients in whom anti-C5 was subsequently stopped experienced a relapse. Altogether these data suggest that long-term eculizumab is highly effective for preventing and treating posttransplant aHUS recurrence. Our study also indicates that anti-C5 should be promptly started if a recurrence occurs.

A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study.

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 +/- 0.32 with TAC/MMF/DAC and 0.03 +/- 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04-0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05-0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.

The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome.

BACKGROUND: Deletion of the complement factor H related 1 (CFHR1) gene is a consequence of non-allelic homologous recombination and has been reported to be more frequent in atypical haemolytic uraemic syndrome (aHUS) patients than in the normal population. Therefore, it is considered a susceptibility factor for the disease. aHUS is associated with hereditary or acquired abnormalities that lead to uncontrolled alternative pathway complement activation. We tested the CFHR1 deletion for association with aHUS in a population of French aHUS cases and controls. Furthermore, we examined the effect of the deletion in the context of known aHUS risk factors. METHODS AND RESULTS: 177 aHUS patients and 70 healthy donors were studied. The number of CFHR1 alleles was quantified by multiplex ligation dependant probe amplification (MLPA). The frequency of the deleted allele was significantly higher in aHUS patients than in controls (22.7% vs 8.2%, p<0.001). The highest frequency was in the subgroup of patients exhibiting anti-factor H (FH) autoantibodies (92.9%, p<0.0001 vs controls) and in the group of patients exhibiting a factor I (CFI) gene mutation (31.8%, p<0.001 vs controls). The CFHR1 deletion was not significantly more frequent in the cohort of aHUS patients when patients with anti-FH IgG or CFI mutation were excluded. CONCLUSIONS: The high frequency of CFHR1 deletion in aHUS patients is restricted to the subgroups of patients presenting with anti-FH autoantibodies or, to a lesser degree, CFI mutation. These results suggest that the CFHR1 deletion plays a secondary role in susceptibility to aHUS.

Hemolytic uremic syndrome due to Shiga toxin-producing Escherichia coli infection.

The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin-producing Escherichia coli (STEC) infection, which has a major outbreak potential. Since the early 2010s, STEC epidemiology is characterized by a decline of the historically predominant O157 serogroup and the emergence of non-O157 STEC, especially O26 and O80 in France. STEC contamination occurs through the ingestion of contaminated food or water, person-to-person transmission, or contact with ruminants or their contaminated environment. The main symptom is diarrhea, which is bloody in about 60% of patients and occurs after a median incubation period of three days. Shiga toxins released by STEC induce a cascade of thrombogenic and inflammatory changes of microvascular endothelial cells. HUS is observed in 5-15% of STEC infection cases, defined by the triad of mechanical hemolytic anemia, thrombocytopenia, and acute renal injury. The diagnosis of STEC infection relies on biological screening for Shiga toxins and STEC in stools and serology. Treatment of STEC-HUS is mainly symptomatic, as no specific drug has proved effective. The effect of antibiotics in STEC infection and STEC-HUS remains debated; however, some bacteriostatic antibiotics might have a beneficial effect. Proofs of evidence of a benefit from complement blockade therapy in STEC-HUS are also lacking. Clinical and bacteriological STEC-HUS surveillance needs to be continued. Ongoing prospective studies will document the role of bacteriostatic antibiotics in STEC infection and STEC-HUS, and of complement blockade therapy in STEC-HUS.

Phylogenetic groups and virulence factors of Escherichia coli strains causing pyelonephritis in children with and without urinary tract abnormalities.

Escherichia coli isolates causing acute pyelonephritis in 93 children (25% with urinary tract abnormalities) were tested for nine virulence factors (papC, papGII, papGIII, sfa/foc, hlyC, cnf1, iucC, fyuA and iroN) and their phylogenetic groups were determined. Isolates lacking papGII were more frequent among patients with urinary tract abnormalities (58% vs. 10%, p 0.0003), as were non-virulent phylogenetic group A isolates (25% vs. 5%, p 0.043). Pyelonephritis caused by less virulent E. coli strains was more frequent among patients with significant urinary tract abnormalities. Further studies are required to determine whether screening for E. coli virulence factors may help to identify children warranting anatomical investigations.

Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome.

PURPOSE: Whereas gastrointestinal symptoms such as vomiting, diarrhea and abdominal pain are common in children suffering from the so-called post-diarrheal form (D+) of hemolytic uremic syndrome (HUS), more serious gastrointestinal complications are rare. We tried to define factors predictive of the severity of gastrointestinal complications post D+ HUS. METHODS: We reviewed the files of all children admitted to our hospital for D+ HUS between 1988 and 2000. We retained those cases with gastrointestinal complications and analyzed the consequences of these complications on the evolution of the children's conditions. RESULTS: Sixty-five children with D+ HUS were admitted to our hospital during this period. Sixteen children developed gastrointestinal complications involving one or more digestive organs: necrosis of the colon or ileum, hemorrhagic colitis, pancreatitis, transient diabetes, hepatic cytolysis and cholestasis, peritonitis and prolapse of the rectum. One child died. CONCLUSION: Gastrointestinal complications of D+ HUS are rare, but they can be lethal, and early surgery may sometimes prove necessary. However, we were not able to demonstrate a correlation between the severity of the gastrointestinal manifestations and the clinical or biological signs accompanying D+ HUS.

[Hemolytic and uremic syndrome and related thrombotic microangiopathies: Epidemiology, pathophysiology and clinics]. / SHU et syndromes de microangiopathie thrombotique apparentés : épidémiologie, physiopathologie et tableaux cliniques.

Thrombotic microangiopathies (TMA) represent an eclectic group of conditions, which share hemolytic anemia and thrombocytopenia as a common defining basis. Remarkable breakthroughs in the physiopathological setting have allowed for a thorough recomposition of the disparate syndromes, which form the constellation of TMA. In this view, clinicians now discriminate thrombocytopenic thrombotic purpura (TTP) defined by a severe deficiency in ADAMTS13, which is rarely associated with a severe renal involvement and the hemolytic and uremic syndrome (HUS) in which renal impairment is the most prominent clinical feature. HUS can result from toxins stemming from bacterial infections of the digestive tract, alternate complement pathway abnormalities, metabolic or coagulation disorders or, lastly, drug and various toxic compounds. The diverse forms of HUS reflect the insights gained in the understanding of the pathophysiological mechanisms underpinning TMA. In this first part, a broad overview of the epidemiological, physiopathological and clinical aspects of HUS and related TMA syndromes is presented.

[Hemolytic and uremic syndrome and related thrombotic microangiopathies: Treatment and prognosis]. / Syndromes hémolytiques et urémiques (SHU) et syndromes de microangiopathie thrombotique apparentés : traitement et pronostic.

Major achievements in the understanding of thrombotic microangiopathies (TMA) have not only resulted in a reclassification of TMA but most of all they have culminated in the design of new treatments and have enabled clinicians to better delineate their prognosis. Recent multicenter studies have improved our understanding of the prognosis of atypical hemolytic and uremic syndromes (aHUS). More specifically, they have highlighted the role of genetic testing on predicting the recurrence of aHUS, the risk of chronic kidney disease and the recurrence following kidney transplantation. A major advance consisted of the identification of the alternative complement pathway in the pathogenesis of aHUS, thus paving the way for the use of the C5a inhibitor eculizumab in this indication. Eculizumab has thereafter dramatically improved the management of patients affected with aHUS. During spring 2011, a great epidemic of entero-hemorrhagic Escherichia coli (EHEC) associated HUS occurred in Germany, providing clinicians the opportunity to examine the relevance of antibiotic prophylaxis, plasma exchange and eculizumab in EHEC-associated HUS. In this work, we herein present advances achieved in the setting of therapeutic management and prognosis in HUS and other related TMA syndromes.

The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts.

BACKGROUND: In both familial and sporadic atypical haemolytic-uraemic syndrome (aHUS), mutations have been reported in regulators of the alternative complement pathway including factor H (CFH), membrane cofactor protein (MCP), and the serine protease factor I (IF). A characteristic feature of both MCP and CFH associated HUS is reduced penetrance and variable inheritance; one possible explanation for this is that functional changes in complement proteins act as modifiers. OBJECTIVE: To examine single nucleotide polymorphisms in both CFH and MCP genes in two large cohorts of HUS patients (Newcastle and Paris). RESULTS: In both cohorts there was an association with HUS for both CFH and MCP alleles. CFH and MCP haplotypes were also significantly different in HUS patients compared with controls. CONCLUSIONS: This study suggests that there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical HUS.

Ten candidate ADAMTS13 mutations in six French families with congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome).

ADAMTS13, the specific von Willebrand factor (VWF)-cleaving metalloprotease, prevents the spontaneous formation of platelet thrombi in the microcirculation by degrading the highly adhesive ultralarge VWF multimers into smaller forms. ADAMTS13 severe enzymatic deficiency and mutations have been described in the congenital thrombotic thrombocytopenic purpura (TTP or Upshaw-Schulman syndrome), a rare and severe disease related to multivisceral microvascular thrombosis. We investigated six French families with congenital TTP for ADAMTS13 enzymatic activity and gene mutations. Six probands with congenital TTP and their family were tested for ADAMTS13 activity in plasma using a two-site immunoradiometric assay and for ADAMTS13 gene mutations using polymerase chain reaction and sequencing. ADAMTS13 activity was severely deficient (< 5%) in the six probands and one mildly symptomatic sibling but normal (> 50%) in all the parents and the asymptomatic siblings. Ten novel candidate ADAMTS13 mutations were identified in all families, showing either a compound heterozygous or a homozygous status in all probands plus the previous sibling and a heterozygous status in the parents. The mutations were spread all over the gene, involving the metalloprotease domain (I79M, S203P, R268P), the disintegrin domain (29 bp deletion in intron/exon 8), the cystein-rich domain (acceptor splice exon 12, R507Q), the spacer domain (A596V), the 3rd TSP1 repeat (C758R), the 5th TSP1 repeat (C908S) and the 8th TSP1 repeat (R1096stop). This study emphasizes the role of ADAMTS13 mutations in the pathogenesis of congenital TTP and suggests that several structural domains of this metalloprotease are involved in both its biogenesis and its substrate recognition process.

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Evidence that modifications of Lp(a) in vivo inhibit plasmin formation on fibrin--a study with individual plasmas presenting natural variations of Lp(a).

In the present study we have investigated the effect of individual variations in the concentration of Lp(a) on plasmin formation at the surface of fibrin. The plasma Lp(a) concentrations from 20 nephrotic children were high at flare-up of the disease (0.43+/-0.45 g/l) and decreased progressively with remission at both 6 weeks (0.28+/-0.24 g/l) and 6 months (0.24+/-0.288 g/l). In contrast, the concentration of plasminogen showed an inverse variation, with low values at flare-up (1.27+/-0.34 microM) and normal values at remission (1.66+/-0.17 microM at 6 weeks and 1.99+/-0.21 microM at 6 months). An increase in plasmin formation (from 0.62+/-0.49 to 0.73+/-0.61, and 0.84+/-0.75 pmol/well) and a decrease in apo(a) binding (from 5.45+/-2.42 to 4.54+/-2.12, and 3.93+/-1.51 fmol/well) on the surface of fibrin, were concomitantly observed from flare-up to remission at 6 weeks and at 6 months, respectively. Values for plasmin formation parallel the amount of plasminogen bound. The low concentration of plasminogen found at flare-up may also have contributed to the increased binding of Lp(a) as indicated by a decrease in the maximal amount of Lp(a) bound (Bmax) to fibrin as a function of plasma plasminogen concentrations. Bmax was 1.51 fmol in the absence of plasminogen and decreased to 1.1 fmol and 0.93 fmol at respectively 1 and 2 microM of plasminogen. Altogether, these data constitute the first quantitative evidence indicating that plasmin formed at the surface of fibrin may vary with modifications of the concentration of Lp(a) in vivo.

The nephropathy associated with male pseudohermaphroditism and Wilms' tumor (Drash syndrome): a distinctive glomerular lesion--report of 10 cases.

We report on 10 children, less than 2 years of age, who presented with a genuine type of glomerulopathy: diffuse mesangial sclerosis. In 5, the nephropathy was associated with male pseudohermaphroditism (MPH) and Wilms' tumor (WT); in 3 with MPH and in 2 with WT. The nephropathy was characterized by its very early onset, between the age of 2 weeks and 18 months. Eight patients presented with a nephrotic syndrome with (7 cases) or without (1 case) hypertension. All, but one, who is in advanced RF at 11 years of age, progressed to chronic or end-stage renal failure (ESRF) within a few months to 2 years from the onset. One additional child presented with advanced renal failure at the age of 8 months and the last one, who was hypertensive, developed an anuria related to thrombosis of renal veins at 1 year of age. Drash syndrome is characterized by the association of a "nephron disorder" with MPH and WT. We propose, on the basis of our histological findings, to extend the concept of Drash syndrome to patients who, in addition to the nephropathy, have either WT or MPH and to consider the distinctive glomerular lesions presented by all these patients as their common denominator. The pathogenesis of this glomerulopathy is obscure. Its early onset, its association with a dysembryoplastic tumor and/or with gonadal dysgenesis both suggest an antenatal dysgenetic process.

Familial hypoplastic glomerulocystic kidney. A new entity?

Two pairs of female siblings of French and Italian origin presented with the histological picture of glomerulocystic kidneys. The cases differ from the patients previously described with glomerulocystic kidneys by the absence of major extrarenal malformations, the reduction of kidney size with absence of renal papillae and by the presence of stable chronic renal failure, starting during the first months of life. Both mothers of the patients also had chronic renal failure with similar urographic abnormalities.

Deficiency of the second component of complement. Its occurrence with membranoproliferative glomerulonephritis.

We studied glomerulonephritis in a child with a deficiency of the second component of complement (C2) who was without clinical or serologic evidence of systemic disease. The clinical course was severe, with malignant hypertension and terminal renal failure when the child was 14 years old. Results of histologic studies were typical of membranoproliferative glomerulonephritis with subendothelial deposits. Immunofluorescence microscopy showed diffuse and intense localization of IgG, C1q, and C4 as granular deposits along the glomerular capillary walls and within the mesanguim. Diffuse deposits of C3 were also found along the capillary walls. Nine months after transplantation, the graft biopsy specimen showed glomerular lesions with IgG, C1q, C4, and C3 deposits, which suggests the possibility of a recurrence. The analysis of the previously reported cases of glomerulonephritis with C2 deficiency showed variable, but generally mild, glomerular lesions. Progression of the glomerulonephritis to severe renal insufficiency, as in the present case, is exceptional.

Bone lesions secondary to benign phaeochromocytoma. Four cases in childhood.

Metaphyseal sclerotic bone changes associated with benign phaeochromocytoma are very rare in childhood. We report four cases, in each of which the radiographic changes returned to normal after removal of the tumour.

[Renal stenosis in hypertensive children. Doppler/arteriographic correlation]. / Sténoses rénales chez les enfants hypertendus. Corrélation Doppler/arteriographie.

To evaluate the reliability of Doppler-ultrasonography in identifying children with renal artery stenosis among those with hypertension, we compared Doppler ultrasonography results in 29 hypertensive children (mean age: 8.3 +/- 4.7 years) with angiography. Doppler-ultrasonography and arteriography were performed within a period less than two months. First, we established normal values in 40 normotensive children (mean age: 8.4 +/- 4.5 years). The diagnosis of renal artery stenosis was settled when maximal systolic velocities where > or = to 1.70 m.s-1. Peak systolic velocities values of Doppler-ultrasonography were significantly higher in patients with proven angiographic renal artery stenosis (3.56 +/- 0.70 m.s-1) than in hypertensive patients with normal renal arteries at angiography (1.02 +/- 0.29 m.s-1, p < 0.0001), and than in normotensive healthy children (1.05 +/- 0.33 m.s-1, p < 0.0001). We observed 3 false negative and 2 false positive diagnoses with Doppler-ultrasonography. Of the 3 false negatives, one had a stenosis on a right and posterior segmental artery and the other had bilateral and multiply intra-renal artery stenosis with few hemodynamic significance. The 2 false positives were due to a sinuous main renal artery and to a technical mistake, respectively. In another patient, Doppler-ultrasonography revealed a tight main renal artery stenosis, not detected by arteriography. Renal artery stenosis was subsequently confirmed by a second arteriography. Our results showed a sensitivity of 88%, a specificity of 93%, a positive predictive value of 92% and a negative predictive value of 89%, demonstrating the reliability of Doppler-ultrasonography for the diagnosis of renal artery stenosis in hypertensive children. With the use of a rigorous methodology and the increasing experience of the operators, diagnostic errors of renal artery stenosis are currently avoidable. Nevertheless, it is not excluded that intra-renal artery stenosis with few hemodynamic significance might be missed by Doppler-ultrasonography.