Interdialytic weight gain in oligoanuric children and adolescents on chronic hemodialysis.

BACKGROUND: Little is known about the clinical impact of interdialytic weight gain (IDWG) on oligoanuric children undergoing chronic hemodialysis (HD). METHODS: We retrospectively assessed IDWG, left ventricular mass index (LVMI) and its changes (ΔLVMI), pre-HD systolic and diastolic blood pressure (DBP), residual urine output, Kt/V, the frequency of intradialytic symptoms, normalized protein catabolic rate, and the 3-month change in the dry weight of 16 hemodialyzed oligoanuric patients with a median age of 14.8 years (range 5.0-17.9). RESULTS: There was a significant correlation between IDWG and median LVMI (r 0.55, p = 0.026), which was 27.3 g/m(2.7) (22.5-37.6) in the patients with a median IDWG of <4 %, and 44.3 g/m(2.7) (28.2-68.7) in those with a median IDWG of >4 % (p = 0.003). None of the four patients with an IDWG of <4 % showed left ventricular hypertrophy, compared with 10 of the 12 patients (83.3 %) with an IDWG of >4 % (p = 0.003); the former also had a better median ΔLVMI (-33.5 % vs -13.0 %; p = 0.02) and a lower median DBP sds (0.24 vs 1.72, p = 0.04). CONCLUSIONS: There is a significant correlation between IDWG and LVMI in pediatric oligoanuric patients on chronic HD: those with an IDWG of >4 % are at a higher risk of left ventricular hypertrophy.

Intradialytic cycling in children and young adults on chronic hemodialysis.

BACKGROUND: Intradialytic exercise has been poorly investigated in pediatric patients on chronic hemodialysis (HD). The aim of this study was to assess the acceptability, safety and efficacy of intradialytic exercise in children and young adults on HD. METHODS: The intradialytic exercise program consisted of 30-min sessions of intra-HD exercise using a cycloergometer two to three times a week for 3 months. Study endpoints were the 6-min walking test (6MWT) distances, lung function, number of stands in the chair test, lower extremity strength (LES), anthropometry, dietary intake, dialysis adequacy, incidence of symptomatic sessions, biochemistry and left ventricular mass index. RESULTS: Ten pediatric patients with a median age of 15.3 (range 9.1-24.2) years were enrolled. Two of these underwent kidney transplantation; the remaining eight completed the study and adapted well to the exercise program. At the end of the 3-month study period, all patients had significantly improved results for the 6MWT (+4.9 %; p < 0.05), chair test (+19 %; p < 0.05) and LES (+29.3 %; p < 0.05). Pre-HD albumin, creatinine and total protein levels and post-HD creatinine levels had also significantly improved. The incidence of symptomatic sessions did not increase during the study period. No adverse events occurred. CONCLUSIONS: Based on our results, we conclude that a 30-min exercise program of intradialytic cycling is feasible for the majority of pediatric patients on chronic HD and will be well accepted. Such an exercise program can lead to a significant improvement in the exercise capacity of this patient population.

Correlates of exercise capacity in pediatric patients on chronic hemodialysis.

OBJECTIVE: Pediatric patients on chronic hemodialysis (HD) are at high risk of inactivity and poor physical fitness. The aim of this study was to assess the main correlates of exercise capacity in a cohort of children and young adults on chronic HD. METHODS: Twelve patients on chronic HD (median age 15.6 years; range 9.1-24.2) underwent a 6-minute walking test (WT), spirometry, a 1-minute chair stand test, and the measurement of lower extremity strength. Demographic data, anthropometry (dry weight, height, body mass index, and skinfold thickness, all expressed as standard deviation scores [SDS]), biochemistry (serum albumin, hemoglobin, creatinine, C-reactive protein, bicarbonate), bioimpedance analysis, HD adequacy indices (spKt/V and eKt/V), left ventricular mass index, and medications were also recorded. RESULTS: There was a significant correlation among the distance covered during the WT (median 552 m, range 186-670), forced vital capacity (87.8% of predicted, range 49.7-136), forced expiratory volume in 1 second (86.7%, range 54.7-126.7), and peak expiratory flow (75.5%, 49.7-105.1). All of these indices positively correlated with the weight SDS (r 0.69-0.85), pre-HD serum creatinine (0.57-0.77), and serum albumin (0.60-0.77) and negatively correlated with weekly erythropoietin dose per kilogram of body weight (from -0.64 to -0.83), with P values ranging from <.05 to <.0005. Lower extremity strength (median 11.5 kg, range 3-15) positively correlated with the number of stands at the chair stand test (median 33, range 18-47; r 0.73, P < .05) and serum albumin (r 0.83, P < .01). Distance at the WT, forced vital capacity, lower extremity strength, and the number of stands at the chair stand test all negatively correlated with C-reactive protein levels (r from -0.81 to -0.67, P < .05). CONCLUSION: Our findings show that protein-energy wasting and chronic inflammation are strongly correlated with the exercise capacity of children and young adults on chronic HD.

Analysis of congenital heart defects in 87 consecutive patients with Brachmann-de Lange syndrome.

Congenital heart defects (CHDs) have been estimated to occur in approximately 20% of patients with Brachmann-de Lange syndrome (BDLS, also known as Cornelia de Lange syndrome, OMIM 122470). We report on the results of a prospective echocardiographic evaluation of a cohort of 87 Italian BDLS patients with longitudinal follow-up from 5 to 12 years. A cardiac anomaly was identified in 29/87 (33.3%) including 28 (32.2%) patients with a structural CHD, and an additional patient (1.2%) with isolated non-obstructive hypertrophic cardiomyopathy (HCM). Of the 28 patients with a CHD, 12 (42.9%) had an isolated obstructive CHD, 10 of which were pulmonary stenosis (36%), 8 (28.6%) had an isolated left to right shunt, and the remainder showed a combination of structural anomalies. Overall incidence of pulmonary stenosis was 39% (11/28). Isolated late-onset mitral or tricuspid valve dysplasia, albeit hemodynamically insignificant, was detected at follow-up examination in 4 (14.3%) patients older than 10 years, previously known to be normal. In contrast to previous studies, only two patients required surgery, one for closure of a large perimembranous ventricular septal defect (VSD) and associated ASD closure (1), and another for VSD closure and relief of pulmonary valve stenosis (1). The remainder are receiving medical follow-up. We believe that the overall frequency (33.3%) and evidence of 4 late onset dysplastic valves anomalies justifies both echocardiographic assessment in all BDLS patients at the first diagnostic assessment, and later on during medical follow-up.

Early Treatment with Quinidine in 2 Patients with Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) Due to Gain-of-Function KCNT1 Mutations: Functional Studies, Clinical Responses, and Critical Issues for Personalized Therapy.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset developmental epileptic encephalopathy resistant to anti-epileptic drugs. The most common cause for EIMFS is a gain-of-function mutation in the KCNT1 potassium channel gene, and treatment with the KCNT1 blocker quinidine has been suggested as a rational approach for seizure control in EIMFS patients. However, variable results on the clinical efficacy of quinidine have been reported. In the present study, we provide a detailed description of the clinical, genetic, in vitro, and in vivo electrophysiological profile and pharmacological responses to quinidine of 2 EIMFS unrelated patients with a heterozygous de novo KCNT1 mutation: c.2849G>A (p.R950Q) in patient 1 and c.2677G>A (p.E893K) in patient 2. When expressed heterologously in CHO cells, KCNT1 channels carrying each variant showed gain-of-function effects, and were more effectively blocked by quinidine when compared to wild-type KCNT1 channels. On the basis of these in vitro results, add-on quinidine treatment was started at 3 and 16 months of age in patients 1 and 2, respectively. The results obtained reveal that quinidine significantly reduced seizure burden (by about 90%) and improved quality of life in both patients, but failed to normalize developmental milestones, which persisted as severely delayed. Based on the present experience, early quinidine intervention associated with heart monitoring and control of blood levels is among the critical factors for therapy effectiveness in EIMFS patients with KCNT1 gain-of-function mutations. Multicenter studies are needed to establish a consensus protocol for patient recruitment, quinidine treatment modalities, and outcome evaluation, to optimize clinical efficacy and reduce risks as well as variability associated to quinidine use in such severe developmental encephalopathy.

A case report of aorto-pulmonary window in an infant born to a diabetic mother.

Several studies have described the association between pre-gestational maternal diabetes and cardiac disease in the newborn. Infants of diabetic mothers have an increased incidence of congenital heart disease, reported between 3% and 6% compared to 0.8% of the general population. A particularly high prevalence of conotruncal defects has been recently described among congenital heart diseases. This group of malformations affects ventricular outflows, aorta, and pulmonary artery and shares a common embryogenic origin. They include persistence of the truncus arteriosus, transposition of great arteries, tetralogy of Fallot, interruption of the aortic arch, and double outlet right ventricle. Aorto-pulmonary window, a rare congenital heart disease belonging to conotruncal malformations, has never been previously described in association with maternal diabetes. We describe the case of a male infant born to a mother suffering from a poorly controlled type 1 diabetes during pregnancy. In the early postnatal life the infant showed respiratory distress, tachycardia, and failure to thrive. He was found to be affected by aorto-pulmonary window that required corrective surgical intervention. .

A rare case of neonatal cyanosis due 'cor triatriatum dexter' and a review of the literature.

Cor triatriatum dexter is a rare cardiac congenital malformation in which a membrane divides the right atrium into two chambers. We describe one case of isolated cor triatriatum dexter, symptomatic for severe central cyanosis, in which the membrane was identified before surgery by means of transthoracic echocardiography alone, and successfully removed surgically at 1 month of life. We discuss this case and review the literature.