Joseph Flynn

Masked Hypertension Associates with Left Ventricular Hypertrophy in Children with CKD

Left ventricular hypertrophy (LVH) associates with increased risk for cardiovascular disease. Hypertension leads to LVH in adults, but its role in the pathogenesis of LVH in children is not as well established. To examine left ventricular mass and evaluate factors associated with LVH in children with stages 2 through 4 chronic kidney disease (CKD), we analyzed cross-sectional data from children who had baseline echocardiography (n = 366) and underwent ambulatory BP monitoring (n = 226) as a part of the observational Chronic Kidney Disease in Children (CKiD) cohort study. At baseline, 17% of children had LVH (11% eccentric and 6% concentric) and 9% had concentric remodeling of the left ventricle. On the basis of a combination of ambulatory and casual BP assessment (n = 198), 38% of children had masked hypertension (normal casual but elevated ambulatory BP) and 18% had confirmed hypertension (both elevated casual and ambulatory BP). There was no significant association between LVH and kidney function. LVH was more common in children with either confirmed (34%) or masked (20%) hypertension compared with children with normal casual and ambulatory BP (8%). In multivariable analysis, masked (odds ratio 4.1) and confirmed (odds ratio 4.3) hypertension were the strongest independent predictors of LVH. In conclusion, casual BP measurements alone are insufficient to predict the presence of LVH in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risk in children with CKD.

Risk factors predicting laryngeal injury in intubated neonates.

We evaluated 95 extubated neonates to determine if certain risk factors could predict the development of laryngeal injury. Risk factors were recorded prospectively during the intubation period and correlated with laryngeal injury determined by laryngoscopy after extubation. Duration of intubation greater than or equal to 7 days and 3 or more intubations significantly predicted injury.

Clinical and Demographic Characteristics of Children With Hypertension

Most information describing hypertension in the young comes from single-center reports. To better understand contemporary demographic and clinical characteristics of hypertensive children and adolescents, we examined baseline data on 351 children aged 1 to <17 years old who were enrolled in 2 multicenter trials of valsartan. Anthropometric, laboratory, and demographic information at randomization was extracted from the clinical trials databases. Summary variables were created and compared for 3 age groups: <6 years (n=90), 6 to <12 years (n=131), and 12 to <17 years (n=130). Comparisons were also made between different etiologies of hypertension and for different anthropometric categories. Children <6 years old were significantly more likely to have secondary hypertension and were significantly less likely to have weight or body mass index >95 percentile compared with older children. Estimated glomerular filtration rate was significantly lower in children <6 years old (90.9 ± 31.8 mL/min per 1.73 m2) than in the other 2 age groups (6 to <12 years, 141.4 ± 42.1 mL/min per 1.73 m2; 12 to <17 years, 138.3 ± 46.0 mL/min per 1.73 m2). Frequency of total cholesterol >95 percentile was significantly lower in children aged <6 years. Diastolic blood pressure index (subject blood pressure÷95 percentile) was significantly higher in children <6 years old (1.1 versus 1.0 in both the 6 to <12 years and 12 to <17 years groups; both P<0.0001). We conclude that hypertensive children <6 years are more likely to have secondary hypertension and to have higher diastolic blood pressure and lower glomerular filtration rate and are less likely to be obese or to have elevated cholesterol than school-aged children or adolescents. These findings emphasize unique aspects of childhood hypertension that should be considered when evaluating children and adolescents with elevated blood pressure and in designing future clinical trials.

BP Control and Left Ventricular Hypertrophy Regression in Children with CKD

In adult patients with CKD, hypertension is linked to the development of left ventricular hypertrophy, but whether this association exists in children with CKD has not been determined conclusively. To assess the relationship between BP and left ventricular hypertrophy, we prospectively analyzed data from the Chronic Kidney Disease in Children cohort. In total, 478 subjects were enrolled, and 435, 321, and 142 subjects remained enrolled at years 1, 3, and 5, respectively. Echocardiograms were obtained 1 year after study entry and then every 2 years; BP was measured annually. A linear mixed model was used to assess the effect of BP on left ventricular mass index, which was measured at three different visits, and a mixed logistic model was used to assess left ventricular hypertrophy. These models were part of a joint longitudinal and survival model to adjust for informative dropout. Predictors of left ventricular mass index included systolic BP, anemia, and use of antihypertensive medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Predictors of left ventricular hypertrophy included systolic BP, female sex, anemia, and use of other antihypertensive medications. Over 4 years, the adjusted prevalence of left ventricular hypertrophy decreased from 15.3% to 12.6% in a systolic BP model and from 15.1% to 12.6% in a diastolic BP model. These results indicate that a decline in BP may predict a decline in left ventricular hypertrophy in children with CKD and suggest additional factors that warrant additional investigation as predictors of left ventricular hypertrophy in these patients.

Predictive value of stridor in detecting laryngeal injury in extubated neonates

We evaluated 73 consecutively extubated neonates for evidence of acute laryngeal injury from intubation. Hoarseness and stridor were graded by a clinical scoring system. Direct laryngoscopy with a flexible fiberoptic broncboscope yielded a 44% incidence of moderate or major laryngeal injury. All patients with stridor had moderate or major injury, as did 38% of patients without stridor. Stridor was quite specific for detecting moderate or major injury but did not identify the type of injury.

Recommended standards for assessing blood pressure in human research where blood pressure or hypertension is a major focus

Recommended standards for assessing blood pressure in human research where blood pressure or hypertension is a major focus

Effect of elevated blood pressure on quality of life in children with chronic kidney disease.

BackgroundAlthough hypertension is known to have an adverse impact on health-related quality of life (HRQoL) in adults, little is known about the effects of hypertension and use of antihypertensive medications on HRQoL in hypertensive children with chronic kidney disease (CKD).MethodsCross-sectional and longitudinal assessment of impact of elevated blood pressure (BP) and antihypertensive medication use on HRQoL scores obtained in children enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Blood pressure was measured both manually and by ambulatory blood pressure monitoring. HRQoL was assessed with the PedsQL survey.ResultsThe study sample included 551 participants with sufficient data for cross-sectional and longitudinal analyses. Cross-sectional analysis of presence of prehypertension or hypertension and impact on HRQoL found mild associations between elevated BP and HRQoL scores with overall PedsQL parent and child scores averaging 79 vs. 76.5 and 83 vs. 78.5, respectively. However, no associations persisted under longitudinal multivariate analysis.ConclusionsDespite apparent small effects of elevated BP on HRQoL at baseline, no association was found between the presence of elevated BP and HRQoL over time in children with mild-to-moderate CKD. In addition, antihypertensive medication use did not appear to have an impact on HRQoL in this population.

Is Blood Pressure Improving in Children With Chronic Kidney Disease?: A Period Analysis

Uncontrolled hypertension in children with chronic kidney disease (CKD) has been identified as one of the main factors contributing to progression of CKD and increased risk for cardiovascular disease. Recent efforts to achieve better blood pressure (BP) control have been recommended. The primary objective of this analysis was to compare BP control over 2 time periods among participants enrolled in the CKiD study (Chronic Kidney Disease in Children). Casual BP and 24-hour ambulatory BP monitor data were compared among 851 participants during 2 time periods: January 1, 2005, through July 1, 2008 (period 1, n=345), and July 1, 2010, through December 31, 2013 (period 2, n=506). Multivariable logistic regression to model the propensity of a visit record being in period 2 as a function of specific predictors was performed. After controlling for confounding variables (age, sex, race, socioeconomics, CKD duration, glomerular filtration rate, proteinuria, body mass index, growth failure, and antihypertensives), no significant differences were detected between time periods with respect to casual BP status (prehypertension: 15% versus 15%; uncontrolled hypertension: 18% versus 17%; P=0.87). Analysis of ambulatory BP monitor data demonstrated higher ambulatory BP indices, most notably masked hypertension in period 2 (36% versus 49%; P<0.001). Average sleep BP index (P<0.05) and sleep BP loads (P<0.05) were higher in period 2. Despite publication of hypertension recommendations and guidelines for BP control in patients with CKD, this study suggests that hypertension remains undertreated and under-recognized in children with CKD. This analysis also underscores the importance of routine ambulatory BP monitor assessment in children with CKD.

Response to "U.S. Preventive Services Task Force Recommendation and Pediatric Hypertension Screening

The U.S. Preventive Services Task Force (USPSTF) recently published their recommendation on pediatric hypertension screening. Based on an evidence review of the literature on 8 key questions, the USPSTF concluded that “there is no direct evidence to suggest that screening for hypertension in children reduces adverse cardiovascular outcomes in adults.” The implication of the USPSTF recommendation is that routine blood pressure (BP) measurement in asymptomatic children and adolescents is of little benefit. The USPSTF publication has provoked considerable alarm among the pediatric community, especially among specialists in cardiovascular and renal disease. There is general concern that the USPSTF report will be interpreted as grounds for abandoning BP measurements in childhood. Indeed, a recent “evidence-based” publication has recommended stopping BP measurement in children. In this issue of The Journal of Clinical Hypertension, Drs Lo, Malaga-Dieguez, and Trachtman propose a series of reasons why, in their opinion, the USPSTF may have done the subspecialty of pediatric hypertension a great service. We disagree and will consider these authors’ main points below. First, the authors conclude that “there is little risk of a policy that advocates deferring routine measurement of BP in asymptomatic children.” As a public health policy, it could be true that the child population risk may be small if BP measurement in asymptomatic children were abandoned. However, child health care is generally provided by physicians or other trained primary care providers, and the focus of primary care is to optimize health in the individual child, not the childhood population. It is well established that elevated BP is a risk factor for adverse health outcomes in individuals. There is sufficient observational data which confirm that this risk holds true for individual children as well as adults. Thus, abandonment of routine childhood BP measurement has the potential to increase risk in individual children by failing to detect conditions that are associated with elevated BP. In considering routine BP measurement from an economic perspective, the authors concur that “practice guidelines that help balance the benefits of a procedure or treatment are valuable even for seemingly innocuous tests such as measurement of BP in children.” It is unclear what the authors’ point is about the costs of routine BP measurement in all children vs the costs of evaluating and managing a child with symptomatic hypertension. All newborn infants undergo routine blood screening for inborn errors of metabolism and metabolic disorders; this screening is more invasive, laboratory costs are not trivial, and the conditions are rare. Relative to what is now standard newborn screening, the economic cost-benefit equation of childhood BP screening is not significant and hardly sufficient to abandon the practice. The authors question whether the USPST has abdicated its responsibility to promote cost-effective procedures that will improve the health of children and undermined efforts to educate doctors and lay people about the importance of hypertension. However, they consider it “premature to answer this question based on what is known.” As noted by Urbina and colleagues, the USFPTF recommendation ignores a substantial body of literature that includes many relevant observational studies, especially those that document intermediate outcomes associated with childhood hypertension such as cardiac hypertrophy, carotid artery thickening, and albuminuria. Thus, there is “evidence” well beyond that deemed acceptable to the USPSTF that contributes knowledge on the evolution of hypertension beginning in childhood. Lo and colleagues, like the USPSTF, have apparently failed to accept much that is known on target organ damage both among adults with known high BP in childhood and among hypertensive children. As an alternative to measuring BP and identifying hypertension, or prehypertension, in childhood, the authors suggest “we could advance global strategies to reduce weight, increase physical activity, and foster healthy lifestyle choices that will correct obesity and in all likelihood restore normal BP. . . .” While this approach may be theoretically plausible, little, if any, success has been achieved despite considerable efforts to approach these goals. Moreover the pace of success with global strategies is too slow for those adolescents who currently have hypertension with or without obesity. As estimated by Brady and colleagues, with elimination of BP screening, from 106,793 to 320,378 adolescents with primary hypertension would not be identified and, considering the number of missed diagnoses, this estimate could be higher. In addition, girls with obesity-associated hypertension who enter young adult childbearing years will have high-risk pregnancies and high-risk offspring. Address for correspondence: Bonita Falkner, MD, Department of Medicine and Pediatrics, Thomas Jefferson University, 833 Chestnut Street, Suite 700, Philadelphia, PA 19107 E-mail: bonita.falkner@jefferson.edu

Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents

BACKGROUND Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. STUDY DESIGN Prospective multicenter observational cohort study. SETTING & PARTICIPANTS 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. PREDICTORS Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. OUTCOMES Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). RESULTS 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. LIMITATIONS Small number of events in glomerular patients and use of internal cross-validation. CONCLUSIONS Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.