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Several circulating biomarkers have been found to play a role in the surveillance and risk stratification of heart failure without congenital heart disease, but these have not been widely studied in patients with single ventricles palliated with a Fontan operation. Imaging predictors of worse outcomes in this population include ventricular dilation and dysfunction. Patients who weighed >30 kg with a Fontan circulation referred for cardiac magnetic resonance imaging were invited to participate in the study. Blood and urine samples were obtained at the time of imaging and multiple conventional and novel biomarkers were measured. A total of 82 patients with a median age of 18 years were enrolled. Among the novel biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T had the strongest correlation with ventricular dilation and dysfunction. NT-ProBNP >100 pg/ml has a sensitivity of 91% for the detection of significant ventricular dilation (end-diastolic volume >120 ml/body surface area 1.3 ) and 82% for detection of ejection fraction <50%. The urinary neutrophil gelatinase-associated lipocalin-2 to creatinine ratio correlated with ejection fraction and estimated glomerular filteration rate. In conclusion, abnormalities in biomarkers of heart failure are common in ambulatory, largely asymptomatic patients with Fontan circulation. NT-ProBNP may serve as a sensitive marker for the identification of patients with significant ventricular dilation or dysfunction. Further work is needed to understand how these easily measured circulating biomarkers may be integrated into clinical care., Competing Interests: Disclosures Dr. Opotowsky has received grant funding from Roche Diagnostics. The authors have no other conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There has been significant research on the genetic and environmental factors of congenital heart defects (CHDs), but few causes of teratogenicity, especially teratogenic mechanisms, can be clearly identified. Metabolomics has a potential advantage in researching the relationship between external factors and CHD., Objective: To find and identify the urinary potential biomarkers of pregnancy (including in the second and third trimesters) for fetuses with CHD based on modified gas chromatograph-mass spectrometer (GC-MS), which could reveal the possibility of high-risk factors for CHD and lay the foundation for early intervention, treatment, and prevention., Methods: Using a case-control design, we measured the urinary potential biomarkers of maternal urine metabolomics based on GC-MS in a population-based sample of women whose infants were diagnosed with CHD (70 case subjects) or were healthy (70 control subjects). SIMCA-P 13.0 software, principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), Wilcoxon-Mann-Whitney test, and logistics regression were used to find significant potential biomarkers., Result: The 3D score graph of the OPLS-DA showed that the CHD and control groups were fully separated. The fitting parameters were R 2 x=0.78 and R 2 y=0.69, and the forecast rate was Q 2 =0.61, indicating a high forecast ability. According to the ranking of VIPs from the OPLS-DA models, we found 34 potential metabolic markers with a VIP > 1, and after two pairwise rank sum tests, we found 20 significant potential biomarkers, which were further used in multifactor logistic regressions. Significant substances, including 4-hydroxybenzeneacetic acid ( OR =4.74, 95% CI: 1.06-21.06), 5-trimethylsilyloxy-n-valeric acid ( OR =15.78, 95% CI: 2.33-106.67), propanedioic acid ( OR =5.37, 95% CI: 1.87-15.45), hydracrylic acid ( OR =6.23, 95% CI: 1.07-36.21), and uric acid ( OR =5.23, 95% CI: 1.23-22.32), were associated with CHD., Conclusion: The major potential biomarkers in maternal urine associated with CHD were 4-hydroxybenzeneacetic acid, 5-trimethylsilyloxy-n-valeric acid, propanedioic acid, hydracrylic acid, and uric acid, respectively. These results indicated that the short chain fatty acids (SCFAs) and aromatic amino acid metabolism may be relevant with CHD.

Background: Industrial chemicals are increasingly recognized as potential developmental neurotoxicants. Di(2-ethylhexyl) phthalate (DEHP), used to impart flexibility and temperature tolerance to polyvinylchloride, and bisphenol A (BPA), used to manufacture polycarbonate, are commonly present in medical devices. The magnitude of exposure in neonates during hospitalization for cardiac operations is unknown., Methods: We quantified urinary concentrations of DEHP metabolites and BPA preoperatively and postoperatively in neonates undergoing cardiac operations and their mothers. Urinary concentrations of these biomarkers reflect recent exposures (half-lives are approximately 6 to 24 hours). Biomarker concentrations in mothers' and infants' preoperative and postoperative samples were compared., Results: Operations were performed in 18 infants (mean age, 5 ± 4 [SD] days). The maternal sample was obtained on postpartum day 4 ± 4. The preoperative urine sample was obtained on day-of-life 4 ± 2 and the postoperative sample on day-of-life 6 ± 4. Mean maternal concentrations for DEHP metabolites and BPA were at the 50th percentile for females in the United States general population. Infant preoperative concentrations of 1 DEHP metabolite and BPA were significantly higher than maternal concentrations. Postoperative concentrations for all DEHP metabolites were significantly greater than preoperative concentrations., Conclusions: There is considerable perioperative exposure to DEHP and BPA for neonates undergoing cardiac operations. Infant concentrations for both BPA and DEHP metabolites were significantly higher than maternal concentrations, consistent with the infant's exposure to medical devices. Further study is needed to determine the potential role of these suspect neurotoxicants in the etiology of neurodevelopmental disability after cardiac operations., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: There is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease. These stand as challenges to systematic investigation and clinical application of biomarkers for adults with CHD. This paper reviews recent studies investigating the use of biomarkers in this population, with emphasis on biomarkers applied in clinical adult CHD care., Recent Findings: A handful of biomarkers have been integrated into adult CHD practice, such as iron studies in cyanotic heart disease and stool alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan circulation. Use of kidney and liver tests has been studied in prognostication of adult CHD patients. A few other biomarkers like natriuretic peptides and troponins seem likely to provide useful information in other ACHD situations based on limited disease-specific data and extrapolation from acquired heart disease. More research is needed to support the robust validity of most existing clinical biomarkers in adult congenital cardiology practice. Until data from larger, prospectively enrolled cohorts are available, clinical use of biomarkers in these patients will require careful interpretation with attention to underlying pathophysiology, as well as detailed understanding of potential pitfalls of specific assays and clinical contexts.

Unlabelled: Introduction Hypoxaemic congenital heart disease (CHD) patients are at higher risk of complications. The aim of this study was to compare and follow-up blood and 24-hour urine analytical data in hypoxaemic and non-hypoxaemic CHD patients., Methods: The inclusion criteria for this study were as follows: patients older than 14 years of age with a structural CHD with or without associated hypoxaemia., Results: In total, 27 hypoxaemic and 48 non-hypoxaemic CHD patients were included in order to compare blood and 24-hour urine analytical data. Among hypoxaemic patients, 13 (48.1%) were male, two (7.4%) had diabetes mellitus, one of whom was a smoker, one (3.7%) had systemic arterial hypertension, and 11 (40.7%) showed pulmonary arterial hypertension. The mean follow-up time was 3.1±1.9 years. Hypoxaemic CHD patients showed higher proteinuria concentrations (g/24 hours) (0.09 (0.07; 0.46) versus 0.08 (0.07; 0.1), p=0.054) and 24-hour albumin excretion rate (µg/min) (16.5 (11.2; 143.5) versus 4.4 (0.0; 7.6), p<0.001) compared with non-hypoxaemic CHD patients; however, no significant differences were found in the proteinuria levels and in the 24-hour albumin excretion rate in CHD patients with associated hypoxaemia, both at baseline and at follow-up. When divided into groups, hypoxaemic patients with palliative shunts showed significantly higher proteinuria concentrations compared with hypoxaemic patients not operated on or with Fontan procedures (p=0.01). No significant differences were seen in 24-hour proteinuria and 24-hour albumin excretion rate during the follow-up of patients with palliative shunts., Conclusions: Hypoxaemic CHD patients have significant higher 24-hour proteinuria concentration and 24-hour albumin excretion rate compared with non-hypoxaemic CHD patients. Among hypoxaemic CHD patients, those with palliative shunts showed the highest 24-hour proteinuria concentrations.

Metabolomics is the quantitative analysis of a large number of low molecular weight metabolites that are intermediate or final products of all the metabolic pathways in a living organism. Any metabolic profiles detectable in a human biological fluid are caused by the interaction between gene expression and the environment. The metabolomics approach offers the possibility to identify variations in metabolite profile that can be used to discriminate disease. This is particularly important for neonatal and pediatric studies especially for severe ill patient diagnosis and early identification. This property is of a great clinical importance in view of the newer definitions of health and disease. This review emphasizes the workflow of a typical metabolomics study and summarizes the latest results obtained in neonatal studies with particular interest in prematurity, intrauterine growth retardation, inborn errors of metabolism, perinatal asphyxia, sepsis, necrotizing enterocolitis, kidney disease, bronchopulmonary dysplasia, and cardiac malformation and dysfunction., (© 2016 Elsevier Inc. All rights reserved.)

Introduction: Acute kidney injury (AKI) is significant problem in children with congenital heart disease (CHD) who undergo cardiac surgery. The economic impact of a biomarker-based diagnostic strategy for AKI in pediatric populations undergoing CHD surgery is unknown. The aim of this study was to perform the cost effectiveness analysis of using serum cystatin C (sCysC), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine liver fatty acid-binding protein (uL-FABP) for the diagnosis of AKI in children after cardiac surgery compared with current diagnostic method (monitoring of serum creatinine (sCr) level)., Materials and Methods: We developed a decision analytical model to estimate incremental cost-effectiveness of different biomarker-based diagnostic strategies compared to current diagnostic strategy. The Markov model was created to compare the lifetime cost associated with using of sCysC, uNGAL, uL-FABP with monitoring of sCr level for the diagnosis of AKI. The utility measurement included in the analysis was quality-adjusted life years (QALY). The results of the analysis are presented as the incremental cost-effectiveness ratio (ICER)., Results: Analysed biomarker-based diagnostic strategies for AKI were cost-effective compared to current diagnostic method. However, uNGAL and sCys C strategies yielded higher costs and lower effectiveness compared to uL-FABP strategy. uL-FABP added 1.43 QALY compared to current diagnostic method at an additional cost of $8521.87 per patient. Therefore, ICER for uL-FABP compared to sCr was $5959.35/QALY., Conclusions: Our results suggest that the use of uL-FABP would represent cost effective strategy for early diagnosis of AKI in children after cardiac surgery.

Objective: To assess the ability of urinary acute kidney injury biomarkers and renal near-infrared spectroscopy (NIRS) to predict outcomes in infants after surgery for congenital heart disease., Methods: Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin C were measured preoperatively and postoperatively in 49 infants younger than 6 months of age. Renal NIRS was monitored for the first 24 hours after surgery. A composite poor outcome was defined as death, the need for renal replacement therapy, prolonged time to first extubation, or prolonged intensive care unit length of stay., Results: Forty-two (86%) patients had acute kidney injury as indicated by at least Acute Kidney Injury Network/Kidney Disease: Improving Global Outcomes (AKIN/KDIGO) stage 1 criteria, and 17 (35%) patients had poor outcomes, including 3 deaths. With the exception of KIM-1, all biomarkers demonstrated significant increases within 24 hours postoperatively among patients with poor outcomes. Low levels of NGAL and IL-18 demonstrated high negative predictive values (91%) within 2 hours postoperatively. Poor outcome infants had greater cumulative time with NIRS saturations less than 50% (60 vs 1.5 minutes; P = .02) in the first 24 hours., Conclusions: Within the first 24 hours after cardiopulmonary bypass, infants at increased risk for poor outcomes demonstrated elevated urinary NGAL, IL-18, and cystatin C and increased time with low NIRS saturations. These findings suggest that urinary biomarkers and renal NIRS may differentiate patients with good versus poor outcomes in the early postoperative period, which could assist clinicians when counseling families and inform the development of future clinical trials., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: The aim of this study was to investigate renal function and injury in infants and young children with congenital heart disease (CHD)., Methods: We prospectively enrolled 58 CHD children aged ≤3 years and 20 age-matched controls and divided these into four groups: Group I, acyanotic CHD (n = 24); Group II, cyanotic CHD with arterial oxygen saturation of >75 % (n = 20); Group III, cyanotic CHD with arterial oxygen saturation of ≤75 % (n = 14); Group IV, normal controls (n = 20). Urinary levels of microalbumin (MA), N-acetyl-ß-D-glucosaminidase (NAG), and α1-microglobulin (α1-MG) corrected by creatinine (UCr) were compared., Results: Children with CHD had elevated urinary α1-MG/UCr levels, with Group III children having the highest level. Groups I and III children had higher urinary NAG/UCr levels than those of Groups II and IV. Urinary MA/UCr levels in the three patient groups were comparable and significantly higher than that in the control group. A α1-MG × 100/ (α1-MG + MA) of <15 %, indicative of glomerular damage, was present in two patients in Group I and one in Group III, but none in Group II., Conclusions: Tubular injury can occur in CHD patients during infancy and early childhood. Among our patient cohort, it was most prominent in children with severe cyanosis. Glomerular injury was detected in some individuals with advanced heart failure or severe cyanosis.

Disorders of the Ras/mitogen-activated protein kinase (MAPK) pathway have an overlapping skeletal phenotype (e.g. scoliosis, osteopenia). The Ras proteins regulate cell proliferation and differentiation and neurofibromatosis type 1 (NF1) individuals have osteoclast hyperactivity and increased bone resorption as measured by urine pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline (Dpd)]. Pyd and Dpd are hydroxylysine-derived crosslinks of collagen found in bone and cartilage and excreted in the urine. Dpd is most abundant in bone. The aim of this study was to evaluate if other syndromes of the Ras/MAPK pathway have increased bone resorption, which may impact the skeletal phenotype. Participants were individuals with Noonan syndrome (n = 14), Costello syndrome (n = 21), and cardiofaciocutaneous (CFC) syndrome (n = 14). Pyridinium crosslinks from two consecutive first morning urines were extracted after acid hydrolysis and analyzed by high performance liquid chromatography. Three separate analyses of covariance were performed to compare Pyd, Dpd, and Dpd/Pyd ratio of each group to controls after controlling for age. Data were compared to 99 healthy controls. The Dpd and the Dpd/Pyd ratio were elevated (p < 0.0001) in all three conditions compared to controls suggesting that collagen degradation was predominantly from bone. The data suggest that the Ras/MAPK signal transduction pathway is important in bone homeostasis., (© 2011 John Wiley & Sons A/S.)

Aims: To evaluate cell catabolism by balance of nitrogen and phosphate, and creatinine excretion in children post-cardiac surgery; to establish protein and energy requirements to minimize catabolism; and to assess nutritional therapy by following these parameters and serial anthropometric measurements., Methods: A prospective observational study of children with congenital heart disease undergoing cardiac surgery. Blood samples and 24-h urine collections were obtained postoperatively for creatinine measurement and nitrogen and phosphate balance. Anthropometric measurements (weight, mid-arm muscle circumference and triceps skinfold thickness) were obtained preoperatively and at paediatric intensive care unit and hospital discharge., Results: Eleven children were studied for 3-10 postoperative days. Anabolism was associated with higher protein and energy intakes compared to catabolism (1.1 vs. 0.1 g/kg/day and 54 vs. 17 kcal/kg/day, respectively). On days with anabolism, phosphate balance was greater compared with that on days with catabolism. Daily creatinine excretion did not correlate with protein balance. Anthropometric measurements did not change significantly over time., Conclusions: Children with congenital heart disease undergoing cardiac surgery achieved anabolism with >55 kcal/kg/day and >1 g/kg/day of protein. Balance of phosphate was useful to monitor cell breakdown. Anthropometric measurements were not valuable to evaluate nutritional therapy in this population., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: To study the intervention of astragalus injection in the kidney injury of infants with congenital heart disease after cardiopulmonary bypass, thus providing a new method for protection of the kidney injury in them., Methods: Forty infants undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to the test group and the control group, twenty in each group. Astragalus Injection (at the dose of 2 mL/kg) was added in the perfusion fluid before giving to infants in the test group before bypass, while the normal saline of the same volume was added in the perfusion fluid before giving to infants in the control group (P < 0.01). The concentrations of serum tumor necrosis factor-alpha (TNF)-alpha, interleukin-6 (IL-6), cystatin C (CysC), and N-acetyl-beta-D-glucosaminidase (NAG) were detected with ELISA at the following time points, i.e., before bypass (T1), by the end of the surgery (T2), 2 h after surgery (T3), 6 h after surgery (T4), and 24 h after surgery (T5)., Results: The serum CysC concentrations were not significantly higher after CPB (P > 0.05). The urinary NAG level increased significantly in the control group after surgery (P < 0.05), but no obvious increase of the urinary NAG level was found in the test group after surgery (P > 0.05). It was obviously lower than that of the control group (P < 0.05). After CPB serum TNF-alpha and IL-6 levels increased significantly in the control group (P < 0.05), while they were lower in the test group than in the control group (P < 0.01)., Conclusions: CPB may result in the renal tubular injury in infants with congenital heart disease. The application of Astragalus Injection before the CPB plays a role in protecting renal tubular functions.

Background: Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been described as an excellent marker of acute kidney injury (AKI) using the enzyme-linked immunosorbent assay (ELISA) from BioPorto Diagnostics, DK. Validation of the ELISA kit and investigation of stability of the NGAL protein is a prerequisite before introducing NGAL as a marker for AKI in clinical research., Methods: Plasma and urine samples from a healthy adult and from 16 children undergoing surgery for congenital heart disease were used to validate the 036 NGAL ELISA kit from BioPorto Diagnostics and study stability of the NGAL protein., Results: Median intra-assay variation in plasma and urine from the healthy adult was <5% and median inter-assay variation was <10%. For children undergoing surgery for congenital heart disease intra-assay variation was <10%. ELISA kit batch-to-batch variation for plasma was 14.6%. We observed excellent results on analysis of linearity and spike-recovery and found no clinically important variation of NGAL measurements throughout the ELISA plate. Haemolysis significantly interfered with measurement of NGAL, whereas repeated thawing or 48 h of 4-5 degrees C-storage before centrifugation and storage at -80 degrees C did not influence NGAL measurements (ANOVA; n.s.). The NGAL protein is stable in plasma for at least 11 months at -80 degrees C., Conclusion: 036 NGAL ELISA kit from BioPorto Diagnostics can be used with acceptable precision for plasma and urine. However, the presence of haemolysis in blood samples or the use of different batches of ELISA kits may seriously decrease the accuracy of measurements.

Background: Bile acid metabolism in preterm infants is yet to be fully characterized. We compared the developmental pattern of urinary bile acid profiles in ten infants born at gestational ages from 25 to 33 weeks with previous data from full-term infants from birth to about 7 months of age., Methods: Gas chromatography-mass spectrometry was performed on serial samples., Results: Total urinary bile acid concentrations gradually increased until 1 to 2 months of age. After this peak of excretion (30 to 60 micromol/mmol creatinine), total urinary bile acid concentrations gradually decreased to less than 20 micromol/mmol creatinine. The percentage of usual bile acids (mainly cholic acid) relative to total urinary total bile acids gradually deceased from approximately 30% at birth to less than 15% at 7 months of age. On the other hand, 1beta-hydroxylated bile acids (mainly 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acid) relative to total urinary bile acids were increased gradually from 60% at birth to reach 70% to 80% at 1 month of age. The percentage of 1beta-hydroxylated bile acids relative to total urinary bile acids then remained stable at a high percentage (70% to 90%) until the age of 7 months., Conclusion: Physiological cholestasis in preterm infants persists longer than in full-term infants. Moreover, as large amounts of cholic and 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acids were detected in urine from preterm infants during this study, the 25-hydroxylation pathway may be particularly important for bile acid synthesis in early preterm infants.

Introduction: Glomerulopathy is a complication of congenital heart disease patients. The risk of developing renal impairment is particularly high in cyanotic patients., Objective: The aim of this study was to determine the prevalence of renal dysfunction and microalbumiuria in adult cyanotic and non cyanotic congenital heart disease patients., Methods: Fourteen cyanotic and 22 noncyanotic congenital heart disease patients were studied in the Adult Congenital Heart Disease Unit at the Complejo Hospitalario Universitario Insular-Materno Infantil. Demographic characteristics, complete blood count, and 24-hour urianalysis were obtained, including abdominal ultrasound in those with cyanosis., Results: No differences were seen between age (years) (27.4 +/- 8.2; 26.4 +/- 8.3; P = .71), sex, size, weight, or glomerular filtration rate (mL/min/1.73 m(2)) (81.1 +/- 22.9 vs. 84.9 +/- 9.2, P = .482) between cyanotic and noncyanotic patients. However, Eisenmenger patients had significantly impaired renal function when compared with noncyanotic patients (73.0 +/- 17.3 vs. 84.9 +/- 9.2 mL/min/1.73 m(2), P = .023). Significant differences were obtained in oxygen saturation (%) (83.8 +/- 5.8 vs. 97.8 +/- 0.8; P = .000), hematocrit (%) (59.3 +/- 8.1 vs. 40.9 +/- 8.5; P = .000), platelets (10(3)/microL) (161.5 +/- 70.5 vs. 277.9 +/- 57.6; P = .000), serum uric acid (mg/dL) (7.5 +/- 2.3 vs. 5.6 +/- 1.5; P = .008) and microalbuminuria (mg/24 hours) (12.8 [0, 700.2] vs. 2.4 [0, 18.9]; P = .000) between cyanotic and noncyanotic patients. Five cyanotic patients (35.7%) had microalbuminuria (>30 mg/24 hours) and three of them (21.4%) proteinuria (>1 g/24 hours). No significant differences were seen between serum and urine parameters between cyanotic patients who had microalbuminuria (>30 mg/24 hours) and those cyanotic patients who did not have it (<30 mg/24 hours)., Conclusions: Renal impairment is frequently seen in congenital heart disease patients, being associated occasionally with proteinuria and microalbuminuria in cyanotic ones.

Objectives: Thyroid hormone alterations after cardiac surgery may be aggravated by the use of iodine antiseptics. We evaluated thyroid function and ioduria in infants with delayed sternal closure (DSC) who are exposed to povidone-iodine for sternal wound protection and compared them with findings in infants after primary sternal closure., Design: Prospective clinical study., Setting: Pediatric cardiac intensive care unit., Patients: Ninety-three infants after cardiac surgery using cardiopulmonary bypass, 60 of them with primary sternal closure and 33 of them with delayed sternal closure., Measurements and Main Results: Thyroid hormones were studied in patients with primary sternal closure immediately after surgery, 5 days and 19 days after surgery, in patients with DSC immediately after surgery, immediately after sternal closure, and 2 wks after sternal closure. Ioduria was evaluated on the first, third, and fifth postoperative days after cardiac surgery with primary sternal closure and immediately after DSC. In both groups of patients, low total triiodothyronine, total thyroxine, thyroxine-binding globulin levels, high reverse triiodothyronine levels, and normal free triiodothyronine, free thyroxine, and thyroid-stimulating hormone levels were recorded immediately after surgery. Concentrations of total triiodothyronine and thyroid-stimulating hormone were lower in the patients with DSC. Five days after primary sternal closure and 2 wks after DSC, all thyroid hormone levels were normal for age. Ioduria after DSC was higher than ioduria after primary sternal closure., Conclusions: Patients with DSC compared with patients with primary sternal closure display more profound thyroid suppression in the immediate postoperative period. The use of povidone-iodine adhesive drapes with single povidone-iodine mediastinal irrigation in patients with DSC is associated with significant iodine absorption but no significant thyroid dysfunction.

In this paper results of the analysis of urine samples of healthy children and children with a congenital cyanotic heart defect and after heart transplantation are presented. The analysis of urine samples was carried out by X-ray fluorescence spectrometry with wavelength dispersion and using CRM urine Seronorm as a reference. It was found that for patients with a congenital cyanotic heart defect the loss of electrolytes like Na, Cl and K was increased. Moreover, urine samples of children from areas of different degree of environmental pollution were analysed. We observed (as expected) higher concentrations of heavy metals in the urine of children from ecological polluted areas.

Objective: There are few data on non-immune nephropathy in cyanotic congenital heart disease reported in the literature. Rheologic changes have been suspected to be involved in the pathogenesis. This study was performed to describe the characteristics of renal functional and hemorheological abnormalities in a large group of patients with cyanotic congenital heart disease., Patients and Methods: Thirty-five cyanotic patients with median oxygen saturation of 82% (range 38-92%), age 18 years (range 5-63 years), and 13 acyanotic controls with atrial septal defect, age 37 years (range 20-66 years) were included. Red cell indices, blood and plasma viscosity were analyzed. Renal function was evaluated with measurements of albumin, alpha1-microglobulin, transferrin, immunoglobuline, and N-acetyl-beta-D-glucosaminidase in the urine., Results: Fifteen cyanotic patients and 1 control patient had pathologic albuminuria (p < 0.05). In cyanotic patients blood and plasma viscosity, erythrocyte count, hemoglobin, and hematocrit were elevated while mean corpuscular volume and mean corpuscular hemoglobin were decreased (p < 0.05). The possible impact of blood hyperviscosity on proteinuria is indicated by multiple regression analysis (odds ratio = 0.5, confidence intervals 22-130, p < 0.05)., Conclusions: Our study shows a coincidence of elevated blood viscosity and proteinuria in patients with cyanotic congenital heart disease. This observation supports the hypothesis that impaired peritubular capillary blood flow with increased intraglomerular blood pressure may add to chronic glomerular dysfunction.

Background: Chronic cyanosis with its associated rheologic changes is a known risk factor for glomerular nephropathy. Therefore, contrast-induced nephrotoxicity should be an important consideration for angiographers comparable to diabetics. On the other hand, progressions in diagnostic and interventional techniques have led to expanded indications and a more widespread use of x-ray contrast agents. The aim of this study was to investigate the risk of contrast-induced nephropathy in the small group of patients with cyanotic heart disease prior to surgical repair., Methods: We investigated 23 cyanotic patients with an oxygen saturation of 82 (50-92)%, age 25 (5-63) years, and 13 control subjects with atrial septal defect, age 37 (20-66) years. Blood viscosity was measured before and after cardiac catherization. Renal damage was evaluated by selective analysis of urinary proteins and enzymes., Results: Before cardiac catheterization, 48% of the cyanotic patients had a moderate glomerulopathy. Cardiac catherization was performed with 3.0 (1.2-6.8) mls/kg non ionic contrast medium. Only one of the 23 patients (4.3%) with normal urinary analysis before cardiac catheterization showed renal damage, which involved tubular and glomerular function. Elevated blood viscosity in cyanotic patients was slightly reduced by the contrast. None of the acyanotic controls had contrast-induced nephropathy., Conclusions: The use of non-ionic contrast medium does not worsen cyanotic glomerulopathy. This finding may be due to the reduction of blood viscosity by the application of the contrast medium. The finding of contrast-induced nephropathy in one patient underlines the importance of monitoring renal function after cardiac catheterization.

Nephropathy is known to occur in patients with long-standing cyanotic congenital heart disease (CCHD). In order to assess the incidence, nature and degree of the problem among such patients, discriminating urine analyses were performed in 26 patients with CCHD, with a mean age of 22 (10-42) y. Ten patients showed reduced glomerular function, six of whom also had advanced glomerulopathy. Glomerular filtration rates were below normal in half of the patients and occurred with glomerular-type proteinuria in five, with tubular-type proteinuria in one and without pathological proteinuria in four. An elevated haematocrit and duration of cyanosis were identified as the main risks factors for the development of glomerulopathy. The risk of developing glomerular lesions rose sharply during the second decade of life. Nephropathy in CCHD is common and the dominant feature is glomerular damage, which is related to the duration of cyanosis and the extent to which the haematocrit is elevated.

The high risk of vaso-occlusive events in children younger than 4 years with cyanotic congenital heart disease and polycythaemia has been attributed to increased thromboxane (Tx) A2 formation. In older children with cyanotic congenital heart disease, however, the risk of vaso-occlusive events is much lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is not disturbed in this age group. We measured urinary excretion of stable index metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic congenital heart disease, and in nine healthy, age-matched control subjects. The patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3-dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2 (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the lower risk of vaso-occlusive events in this age group as compared with younger children. In addition, our results suggest that chronic hypoxaemia may affect the in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.

This study examines the exacerbating factors of hyperuricaemia in patients with cyanotic congenital heart disease (CCHD). We studied 59 CCHD patients aged 1 month-30 years. The following variables were assessed: serum uric acid levels, red blood cell count, haemoglobin, hematocrit, partial oxygen pressure and arterial oxygen saturation. Uric acid excretion and renal function were also measured in ten patients with serum levels of uric acid greater than 8 mg/dl (hyperuricaemia group). Serum uric acid level correlated significantly with age and severity of polycythaemia. However, it did not correlate with partial oxygen pressure or arterial oxygen saturation. Uric acid excretion was measured in hyperuricaemia group. Urinary uric acid excretion (24 h) was within normal limits in infants but markedly lower in patients over 15 years of age. The aetiology of hyperuricaemia and decreased uric acid fractional excretion and clearance in infants appears to be secondary to diminished excretion of uric acid in concert with uric acid overproduction. Hyperuricaemia in adolescents and adults with CCHD, however, results mainly from age-related impairment of uric acid excretion.

Objective: To evaluate whether circulating endothelin, a peptide that is thought to play a part in mediating vascular tone, might be high in pulmonary hypertensive congenital heart disease., Design: A prospective study with a radioimmunoassay technique to estimate urinary and plasma endothelin concentrations., Setting: A supraregional referral centre for patients with congenital heart disease., Patients: The 12 hour urinary endothelin concentration in young children with an increased pulmonary blood flow (n = 24, median age eight months) were compared with those in children with right ventricular outflow tract obstruction (n = 14, median age 1.5 years) and with those in healthy controls (n = 16, median age 1.8 years). The concentrations were also measured in adolescents with irreversible pulmonary vascular disease (n = 17, median age 18 years) and compared with those in controls of similar age (n = 19, median age 18.5 years). Also the plasma concentrations in the left atrium and pulmonary artery were measured in young children with either high (n = 11, median age 10.8 months) or low (n = 5, median age 1.0 year) pulmonary blood flow, in the peripheral arterial and venous blood of young children with either high (n = 13, median age 10.8 months) or low (n = 6 median age 1.9 years) pulmonary blood flow, and in the peripheral venous blood of seven healthy young children (median age 1.7 years)., Results: The urinary excretion of endothelin was similar in young children of a similar age, whether they had high, low, or normal pulmonary blood flow. Also, urinary endothelin excretion in older patients with irreversible pulmonary vascular disease was similar to that in normal subjects of similar age. Urinary endothelin excretion in normal young children, however, was significantly greater than that in normal older subjects (p = 0.0001). There was no transpulmonary or arteriovenous difference detected in either children with high or low pulmonary blood flow, and plasma concentrations sampled from the left atrium, pulmonary artery, and systemic artery and vein were similar in both groups., Conclusion: There was no evidence to implicate circulating endothelin in the pathogenesis of pulmonary vascular disease.

Background: Children with cyanotic congenital heart disease and pulmonary outflow tract obstruction have shortened platelet survival times and are susceptible to thrombosis and organ infarction. Thromboxane A2 and prostacyclin have opposing actions on platelet aggregability and an imbalance in their biosynthesis might contribute to the pathophysiology of these complications., Methods: Biosynthesis of thromboxane A2 and prostacyclin was investigated in 16 children (4-32 months, median 18 months) with cyanotic congenital heart disease and pulmonary outflow tract obstruction and compared with 16 healthy children of a similar age (6-34 months, median 24 months). Urinary excretion of 2,3-dinor-thromboxane B2 (a metabolite of thromboxane A2) and of 2,3-dinor-6-oxo-prostaglandin F1 alpha (a metabolite of prostacyclin) was measured., Results: The children with cyanotic congenital heart disease and pulmonary outflow tract obstruction excreted more 2,3-dinor-thromboxane B2 than the healthy children: 916(163) compared with 592(122) ng/g creatinine (mean(SEM); 2p = 0.014). The ratio of excretion of 2,3-dinor-thromboxane B2 to 2,3-dinor-prostaglandin F1 alpha was greater in the patients than in the healthy control group (2.38(0.28) v 1.3(0.22)) (2p = 0.002)., Conclusion: The balance between biosynthesis of prostacyclin and of thromboxane A2 is abnormal in children with cyanotic congenital heart disease and pulmonary outflow tract obstruction and favours platelet aggregation and vasoconstriction.

In a prospective study, 10 children with congenital heart disease were studied before and after surgery (24-48 h). Mean age and weight, type of disease and surgery performed are described in Table 1. Six patients had acyanotic disease and 4 were cyanotic. Before surgery, the acyanotic group (AG) showed hyperuricemia compared to normal children of the same chronological age (mean +/- SE: 5.53 +/- 0.42 vs 4.27 +/- 0.22, p less than 0.02). Initial seric creatinine (sCr), increased in 3 patients of the AC and in the 4 patients of the cyanotic group (CG) compared to normal values of sCr for height (AG: 0.47 +/- 0.05 vs 0.34 +/- 0.03, p less than 0.05; CG: 0.63 +/- 0.05 vs 0.38 +/- 0.05, p less than 0.01). Post-surgery, sCr and serum uric acid (sUA) increased significantly at 24 and 48 h in both groups (Fig 1); at 24 h the increment in sUA in the AG was higher than that in the CG (p less than 0.05). There was a direct and significant correlation between the increment in sUA and sCr in the AG (Fig. 2). The urine excretion of uric acid paralleled the increment of sUA in the CG (Table 2). Fractional excretion of, sodium (FENa) was less than 1% and greater than 1% in the AG and the CG, respectively, being the basal FENa of the AG significantly lower (Table 3).(ABSTRACT TRUNCATED AT 250 WORDS)

The addition of amiodarone to digoxin therapy in nine children caused a sharp increase in digoxin serum concentrations (68% to 800%) in the presence of preserved serum creatinine and BUN concentrations. Digoxin half-life was prolonged. Digoxin accumulation could be attributed in part to the decrease in the renal clearance of digoxin resulting from inhibited tubular secretion of the drug and to the reduction in the distribution volume of digoxin caused by amiodarone. Creatinine clearance was not affected by amiodarone. This interaction appears to be more acute in children than in adults, presumably because of the more important role of the renal tubular secretion of digoxin in children. Whenever digoxin and amiodarone therapy are combined, the digoxin serum concentration should be monitored carefully, with appropriate reduction of the digoxin dose.