Why multidisciplinary clinics should be the standard for treating chronic kidney disease

In adults, strong evidence indicates that slowing progression of chronic kidney disease (CKD) requires an integrated, multidisciplinary approach. In children, however, this approach has not been studied. This editorial commentary to the study by Ajarmeh et al in this volume of Pediatric Nephrology highlights how a dedicated, multidisciplinary team of physicians, nurses, pharmacists, dieticians, social workders and clinic data managers slowed the progression of CKD in children to a remarkable degree. We discuss the strengths and limitations of the study and its cost implications, as well as the issue of determining the optional complement of physicians and allied health care professionals in such clinics. Our calculations indicate that the additional costs of such clinics would be recovered in one year, even if the progession of CKD were to be delayed by 1 year in only 2% of affected children. Here, we call on the international pediatric nephrology community to establihs guidelines for forming multidisciplinary clinics throughout the world. © IPNA 2012

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Perinatal Factors Associated with Cardiovascular Disease Risk among Preschool-Age Children in the United States: An Analysis of 1999–2008 NHANES Data

We examined the relationships between selected perinatal and early infancy factors (maternal smoking during pregnancy, infant low birthweight, breastfeeding, and early introduction of solid foods [<6 months of age] and increased BMI [≥85th, ≥95th percentiles for age, sex]), waist circumference (WC), C-reactive protein (CRP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and decreased HDL cholesterol during early childhood. The population-based sample included 3,644 3-to-6-year-old Non-Hispanic White (NHW), Hispanic, and Non-Hispanic Black (NHB) children who participated in the 1999–2008 National Health and Nutrition Examination Surveys. Analysis showed that breastfeeding was significantly protective against early childhood obesity (OR 0.43, 95% CI, 0.27–0.69) and the highest quintile for WC (OR 0.58, 95% CI, 0.37–0.32) among NHW, and against the highest quintile of non-HDL cholesterol among NHB (OR 0.56, 95% CI, 0.32–0.98). Additionally, NHW children were significantly more likely to be obese (OR 2.22, 95% CI 1.30–3.78) and have higher CRP levels (OR 1.63, 95% CI, 1.05–2.51) if their mothers smoked during pregnancy. These results support the observation that breastfeeding may be protective against early childhood obesity while maternal smoking during pregnancy is a risk factor for obesity and increased CRP levels among NHW young children

Maternal age and other predictors of newborn blood pressure

Objective To investigate perinatal predictors of newborn blood pressure. Study design Among 1059 mothers and their newborn infants participating in Project Viva, a US cohort study of pregnant women and their offspring, we obtained five systolic blood pressure readings on a single occasion in the first few days of life. Using multivariate linear regression models, we examined the extent to which maternal age and other pre- and perinatal factors predicted newborn blood pressure level. Results Mean (SD) maternal age was 32.0 (5.2) years, and mean (SD) newborn systolic blood pressure was 72.6 (9.0) mm Hg. A multivariate model showed that for each 5-year increase in maternal age, newborn systolic blood pressure was 0.8 mm Hg higher (95% CI, 0.2, 1.4). In addition to maternal age, independent predictors of newborn blood pressure included maternal third trimester blood pressure (0.9 mm Hg [95% CI, 0.2, 1.6] for each increment in maternal blood pressure); infant age at which we measured blood pressure (2.4 mm Hg [95% CI 1.7, 3.0] for each additional day of life); and birth weight (2.9 mm Hg [95% CI, 1.6, 4.2] per kg). Conclusions Higher maternal age, maternal blood pressure, and birth weight were associated with higher newborn systolic blood pressure. Whereas blood pressure later in childhood predicts adult hypertension and its consequences, newborn blood pressure may represent different phenomena, such as pre- and perinatal influences on cardiac structure and function. Development of risk for adult cardiovascular disease begins very early in life, even before birth.1 Data are scarce, however, regarding blood pressure in the newborn period, which may reflect pre- and perinatal influences on cardiac structure and function. The few studies that have examined determinants of newborn blood pressure suggest a direct association with birth weight,2.; 3.; 4.; 5.; 6.; 7.; 8.; 9. ; 10. in contrast to the inverse association seen with older infants, children, and adults.11 However, most of these studies have at least one important limitation, such as a relatively small sample size of term newborns, lack of data on potentially confounding variables, and limited data on maternal predictors. Maternal age is of particular interest given the known associations of advanced age with adverse reproductive outcomes, including reduced fertility, preterm birth, impaired fetal growth, multiple birth, and congenital anomalies.12.; 13. ; 14. The additional associations of advanced maternal age with diabetes and hypertension,15. ; 16. with possible diminished uterine vascular and placental function,17. ; 18. and in at least two reports with blood pressure level in childhood and in adolescence19. ; 20. warrant examination of its influence on newborn blood pressure. The purpose of this analysis was to investigate associations of pre- and perinatal factors, including maternal age, with systolic blood pressure level during the first few days of life among members of Project Viva, a cohort study of pregnant women and their children

Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation

AbstractObjectivesWe studied the outcomes of pediatric patients diagnosed with dilated cardiomyopathy (DCM) and their relation to epidemiologic and echocardiographic variables at the time of presentation.BackgroundThe outcome of pediatric DCM patients ranges from recovery to a 50% to 60% chance of death within five years of diagnosis. The impact of heart transplantation and other emerging therapies on the outcomes of pediatric DCM patients is uncertain.MethodsWe performed a retrospective study of the outcomes in 91 pediatric patients diagnosed with DCM from 1990 to 1999. Routine therapy included use of digoxin, diuretics, angiotensin-converting enzyme inhibitors, and heart transplantation.ResultsAt the time of last follow-up, 11 patients (12%) had died without transplantation; 20 (22%) underwent transplantation; 27 (30%) had persistent cardiomyopathy; and 33 (36%) had recovery of left ventricular systolic function. Overall actuarial one-year survival was 90%, and five-year survival was 83%. However, actuarial freedom from “heart death” (death or transplantation) was only 70% at one year and 58% at five years. Multivariate analysis found age <1 year (hazard ratio 7.1), age >12 years (hazard ratio 4.5), and female gender (hazard ratio 3.0) to be significantly associated with a greater risk of death or transplantation and a higher left ventricular shortening fraction at presentation (hazard ratio 0.92), with a slightly decreased risk of death or transplantation.ConclusionsPediatric DCM patients continue to have multiple outcomes, with recovery of left ventricular systolic function occurring most frequently. Utilization of heart transplantation has led to improved survival after the diagnosis of pediatric DCM

Cardiovascular Effects in Childhood Cancer Survivors Treated with Anthracyclines

Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart failure, coronary artery disease, and cerebrovascular accidents compared to the general population. The specific mechanisms of anthracycline cardiotoxicity are complex and remain unclear. Hence, determining the factors that may increase susceptibility to cardiotoxicity is of great importance, as is monitoring patients during and after treatment. Additionally, treatment and prevention options, such as limiting cumulative dosage, liposomal anthracyclines, and dexrazoxane, continue to be explored. Here, we review the cardiovascular complications associated with the use of anthracyclines in treating malignancies in children and discuss methods for preventing, screening, and treating such complications in childhood cancer survivors

Myocardial Alternative RNA Splicing and Gene Expression Profiling in Early Stage Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome

Differences in Presentation and Outcomes between Children with Familial Dilated Cardiomyopathy and Children with Idiopathic Dilated Cardiomyopathy: A Report from the Pediatric Cardiomyopathy Registry Study Group

Research comparing the survival of children with familial dilated cardiomyopathy (FDCM) to that of children with idiopathic dilated cardiomyopathy (IDCM) has produced conflicting results

Joint generalized estimating equations for multivariate longitudinal binary outcomes with missing data: an application to acquired immune deficiency syndrome data

In a large, prospective longitudinal study designed to monitor cardiac abnormalities in children born to HIV-infected women, instead of a single outcome variable, there are multiple binary outcomes (e.g., abnormal heart rate, abnormal blood pressure, abnormal heart wall thickness) considered as joint measures of heart function over time. In the presence of missing responses at some time points, longitudinal marginal models for these multiple outcomes can be estimated using generalized estimating equations (GEE) (Liang and Zeger, 1986), and consistent estimates can be obtained under the assumption of a missing completely at random (MCAR) mechanism. When the missing data mechanism is missing at random (MAR), that is the probability of missing a particular outcome at a time-point depends on observed values of that outcome and the remaining outcomes at other time points, we propose joint estimation of the marginal models using a single modified GEE based on an EM-type algorithm. The proposed method is motivated by the longitudinal study of cardiac abnormalities in children born to HIV-infected women and analyses of these data are presented to illustrate the application of the method. Further, in an asymptotic study of bias, we show that under an MAR mechanism in which missingness depends on all observed outcome variables, our joint estimation via the modified GEE produces almost unbiased estimates, provided the correlation model has been correctly specified, whereas estimates from standard GEE can lead to substantial bias