Joseph T. Flynn

Update: Ambulatory Blood Pressure Monitoring in Children and Adolescents: A Scientific Statement From the American Heart Association

Ambulatory blood pressure monitoring (ABPM) has established roles in the evaluation and management of hypertension in adults but has only been applied to children and adolescents more recently.1 In 2008, the American Heart Association (AHA) issued the first set of consensus recommendations for performance and interpretation of ABPM in pediatrics. Since then, ABPM has found increasing use in children and adolescents, as recently summarized.2 The present document updates the 2008 AHA statement on the use of ABPM in the pediatric population3 with additional data published since the release of that report and also presents a revised interpretation schema. Because no outcome studies are yet available relating ABPM levels in children to outcomes such as myocardial infarction or stroke, these guidelines are largely driven by expert opinion, although they are also informed by available pediatric data on ABPM and surrogate markers of cardiovascular disease. ### Epidemiology of Hypertension High blood pressure (BP) is the leading risk factor–related cause of death throughout the world, accounting for 12.8% of all deaths, including 51% of stroke deaths and 45% of coronary heart disease deaths.4 In the United States, 33.0% of adults >20 years of age have hypertension.5 As our population continues to age, this will only increase, because 90% of people with normal BP at age 55 years will go on to develop hypertension in their lifetimes.6 The prevalence of hypertension in youths is also on the rise. US National Health and Nutrition Examination Survey (NHANES) data from 1963 to 2002 showed a 2.3% increase in prehypertension and a 1% increase in hypertension from 1988 to 1999, with higher rates in non-Hispanic blacks and Mexican Americans.7 In fact, the entire distribution of childhood BP has shifted upward in the United States by 1.4 mm Hg for systolic BP (SBP) and 3.3 …

Neonatal hypertension: diagnosis and management

Abstract Hypertension in the term or preterm neonate may be seen in up to 2% of all infants cared for in the modern neonatal intensive care unit. Although the definition of hypertension in this age group has not been completely standardized, recent studies have provided new normative data that may be used to facilitate identification of such infants. Common causes of hypertension in neonates include thromboembolic events related to umbilical catheterization, congenital problems such as aortic coarctation, structural renal malformations and renovascular disease, as well as acquired renal disease and certain medications. A careful history and physical examination will usually identify the probable cause in most cases without the need for extensive laboratory or radiologic testing. Therapy of neonatal hypertension should be tailored to the severity of the blood pressure elevation, and to the underlying cause of hypertension as appropriate. A wide range of therapeutic agents are now available for management of neonatal hypertension in both the acute and chronic settings. In most cases hypertension will resolve, but some infants may require prolonged treatment.

RENAL TRANSPLANTATION IN CHILDREN WITH SEVERE LOWER URINARY TRACT DYSFUNCTION

PURPOSE Renal transplantation in children with end stage renal disease due to congenital urological malformations has traditionally been associated with a poor outcome compared to transplantation in those with a normal urinary tract. In addition, the optimal urological treatment for such children remains unclear. To address these issues, we retrospectively reviewed our experience with renal transplantation in this population. MATERIALS AND METHODS Between 1986 and 1998, 12 boys and 6 girls a mean age of 8.4 years with a severe dysfunctional lower urinary tract underwent a total of 15 living related and 6 cadaveric renal transplantations. Urological anomalies included posterior urethral valves in 8 cases, urogenital sinus anomalies in 4, the prune-belly syndrome in 2, and complete bladder duplication, ureterocele, lipomeningocele and the VATER syndrome in 1 each. In 11 children (61%) bladder augmentation or continent urinary diversion was performed, 2 (11%) have an intestinal conduit and 5 (28%) have a transplant into the native bladder. RESULTS In this group patient and overall allograft survival was 100 and 81%, respectively. These values were the same in all children who underwent renal transplantation at our center during this era. In the 17 children with a functioning transplant mean serum creatinine was 1.4 mg./dl. Technical complications occurred in 4 patients (22%), including transplant ureteral obstruction in 2 as well as intestinal conduit stomal stenosis and Mitrofanoff stomal incontinence. CONCLUSIONS Renal transplantation may be successfully performed in children with end stage renal disease due to severe lower urinary tract dysfunction. Bladder reconstruction, which may be required in the majority of these cases, appears to be safe when performed before or after the transplant. A multidisciplinary team approach to surgery is advantageous.

Choice of dialysis modality for management of pediatric acute renal failure

Abstract. Acute renal failure in children requiring dialysis can be managed with a variety of modalities, including peritoneal dialysis, intermittent hemodialysis, and continuous hemofiltration or hemodiafiltration. The choice of dialysis modality to be used in managing a specific patient is influenced by several factors, including the goals of dialysis, the unique advantages and disadvantages of each modality, and institutional resources. This review will examine these aspects of acute renal failure management, with the goal of providing practical guidance regarding modality selection to the physician involved in the management of pediatric acute renal failure.

Calcium channel blockers: pharmacology and place in therapy of pediatric hypertension

Abstract The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus A Scientific Statement From the American Heart Association

The rates of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are increasing in youth.1 In the past 10 years, guidelines for the identification and management of cardiovascular disease (CVD) risk factors in youth with diabetes mellitus have been published by multiple professional organizations, including the American Diabetes Association (ADA),2,3 the American Heart Association (AHA),4,5 the American Academy of Pediatrics,6 the International Society of Pediatric and Adolescent Diabetes (ISPAD),7 and the Pediatric Cardiovascular Risk Reduction Initiative.8 This scientific statement summarizes and interprets these guidelines and new developments in the field in the past decade and outlines future research and clinical needs to improve cardiovascular health and risk factor management in youth with diabetes mellitus. Additional goals for this statement are to increase awareness of CVD risk factors and their identification, prevention, and treatment and to improve cardiovascular health in youth with diabetes mellitus by encouraging advancement in research and clinical care, including understanding and implementing current CVD guidelines. Improving cardiovascular health in youth with diabetes mellitus has important public health implications; therefore, this statement aims to reach healthcare providers in diabetes mellitus, cardiology, and related fields. (Note: The sections within this scientific statement are organized by diabetes mellitus type, when possible, with brief summary statements concluding each section. Multiple definitions for CVD are used in the cited articles. Readers of this statement should include risk factors, surrogate markers, and end-organ damage under this umbrella term of CVD.) ### Type 1 Diabetes Mellitus Multiple studies document an increase of 2% to 5% annually in the incidence of T1DM worldwide.9 The SEARCH for Diabetes in Youth (SEARCH) study estimated that there were 166 018 to 179 388 youth with T1DM in the United States in 2010.1 Worldwide, rates of T1DM differ …

Efficacy and Safety of the Angiotensin Receptor Blocker Valsartan in Children With Hypertension Aged 1 to 5 Years

The efficacy and safety of valsartan were studied in 90 children (mean age: 3.2 years; 60% male; 30% black) with systolic blood pressure (SBP) ≥95th percentile. Nineteen percent received valsartan in addition to previous antihypertensive therapy. Subjects were randomly assigned to low-, medium-, or high-dose valsartan for 2 weeks (phase 1) and then reassigned randomly to placebo or to remain on the same valsartan dose for 2 additional weeks (phase 2). After this, subjects were enrolled into a 52-week, open-label phase during which valsartan was dosed to achieve SBP <95th percentile. Statistically significant reductions in SBP and diastolic blood pressure of ≈8.5 mm Hg and 5.7 mm Hg, respectively, were observed at the end of phase 1 in all of the valsartan dose groups. SBP and diastolic blood pressure were also significantly lower during phase 2 in valsartan recipients compared with placebo recipients. SBP <95th percentile was achieved in 77.3% of subjects during the open-label phase. Adverse events were minor and occurred at similar frequencies in each of the 3 dose groups in phase 1 and at equal frequencies in the valsartan and placebo arms in phase 2. Serious adverse events and drug-related adverse events occurred infrequently during both the double-blind (2.2% and 5.6%, respectively) and open-label (14.8% and 6.8%, respectively) portions of the study. Valsartan treatment had no demonstrable negative effects on growth and development. In this study, the first trial of an antihypertensive agent conducted in children <6 years of age, valsartan effectively lowered SBP and diastolic blood pressure compared with placebo.

Evaluation and management of hypertension in childhood

Hypertension, a relatively uncommon problem in childhood except in certain groups of children, is an important cardiovascular risk factor that can have significant health implications, especially the tendency for an elevated blood pressure in childhood to predict the development of adult hypertension. Common causes of childhood hypertension include renal and cardiac disease, as well as essential hypertension in adolescents. Given these factors, it is usually possible to evaluate the hypertensive child in a focused manner that should reveal not only the underlying cause of hypertension, but also its severity. Treatment should incorporate non-pharmacologic approaches as well as antihypertensive medications, and should take into account other cardiovascular risk factors such as hyperlipidemia. This review highlights these and other important issues in the evaluation and management of hypertensive children, and provides practical guidance to the practitioner involved in caring for such patients.

Treatment of hypertensive children with amlodipine

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.

Carotid Intima-Media Thickness in Children with CKD: Results from the CKiD Study

BACKGROUND AND OBJECTIVES In adults, increased carotid intima-media thickness (cIMT) as assessed by ultrasonography is a valid predictor of cardiovascular events. Children with CKD are known to be at increased cardiovascular risk. This study sought to identify cardiovascular risk factors associated with increased cIMT in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional analysis of cIMT obtained after 12 months of follow-up of 101 children aged 2-18 years with mild to moderate CKD (median GFR 42.9 ml/min per 1.73 m(2)) in the Chronic Kidney Disease in Children cohort study enrolled between April 2005 and September 2009 and 97 healthy pediatric controls between January 2003 and December 2008. An average of six standardized B-mode ultrasound measurements constituted the overall cIMT measurement. RESULTS The median cIMT was 0.43 mm (interquartile range, 0.38-0.48) compared with 0.41 mm in healthy controls (P=0.03 for difference). After multivariable adjustment, the median cIMT was 0.02 mm (95% confidence interval [CI], 0.01-0.05) larger than that of the healthy controls. In a multivariable linear regression analysis, dyslipidemia and hypertension were associated with 0.05 mm (95% CI, 0.01-0.08) and 0.04 mm (95% CI, 0.003-0.08) greater mean cIMT, respectively. Body mass index, CKD etiology, GFR, birth weight, pubertal status, calcium, phosphorus, sex, and race were not associated with cIMT. CONCLUSIONS cIMT is significantly elevated among children with CKD, as is the prevalence of other cardiovascular risk factors. Of these risk factors, hypertension and dyslipidemia are significantly associated with increased cIMT.