Ellen R. Brooks

Association of body mass with dietary restraint and disinhibition

The relationship of disinhibition and dietary restraint with body mass was studied in a sample of 293 women. Results suggested that higher body mass was associated with an interaction of disinhibition and dietary restraint. The association of disinhibition with higher body mass was moderated by increased dietary restraint. Symptoms of an eating disorder were more strongly associated with disinhibition than with dietary restraint. These results suggest that dieting may moderate the increased body mass associated with overeating. Psychological and eating problems associated with dietary restraint were found to be of less significance than those associated with disinhibition.

The effects of caffeine on graded exercise performance in caffeine naive versus habituated subjects.

SummaryThe physiological effects of caffeine on subjects habituated to caffeine is relatively unstudied compared to those of caffeine naive subjects during graded exercise. Thus, the purpose of this investigation was to determine the effects of caffeine on maximal oxygen consumption (VO2max) and the anaerobic threshold in these two populations. Seventeen moderately trained males were classified according to caffeine usage: (1) caffeine consumption 25 mg·day−1 or less (CN) (n=8) or (2) caffeine consumption above 300 mg·day−1 (CH) (n=9). The subjects were tested post-absorptive on the same cycle ergometer on three occasions with 7 days separating the tests. One hour before each test the subject ingested either a gelatin capsule (C); 3 mg·kg−1 body weight of caffeine (C3); or 5 mg·kg−1 body weight of caffeine (C5). The subject then performed an incrementalVO2max test beginning at 50 W and the work rate was increased 30 W every 2 min until the subject could not maintain the power output. Serial venous blood samples were drawn over 30 s at the end of each stage. The CN group significantly increased resting heart rate (fc) and expired ventilation volume (VE) after C3 and C5 andVO2 after C5. No significant differences were found for exerciseVE,VO2, respiratory excharge ratio,fc or time to exhaustion. There were no significant differences (P < 0.05) in the lactate threshold or the ventilatory threshold between treatment in either group. The CH subjects showed a significant increase (P<0.05) in resting plasma free fatty acid (FFA) concentration only during the C3 and C5 treatments. Plasma FFA levels were significantly increased (P < 0.05) at all times during C3 and C5 treatment in the CN subjects when compared to the control values. These data indicate that caffeine has no effect onVO2max or the anaerobic threshold seen during incremental, graded exercise. However, resting metabolism and ventilation, and both resting and exercise plasma FFA are increased in CN subjects.

Methylated arginine derivatives in children and adolescents with chronic kidney disease

Asymmetric dimethylarginine (ADMA), a methylated L-arginine (Arg) derivative is associated with endothelial dysfunction, vasoconstriction, and hypertension in animals and humans. We examined the relationship between these derivatives, estimated glomerular filtration rate (eGFR), and awake (AW) and asleep (AS) blood pressure (BP) load in children and adolescents (n = 28) with stage 2–3 chronic kidney disease (CKD) and in matched intra-familial controls (n = 10). Plasma L-Arg, ADMA, and symmetric dimethylarginine (SDMA) levels were measured by high-performance liquid chromatography–tandem mass spectrometry. Subjects wore a 24-hr ambulatory BP monitor with BP load >95th percentile. ADMA, SDMA/ADMA ratio and SDMA were 38–200% higher in CKD patients while L-Arg/ADMA and L-Arg/SDMA ratios and the L-Arg level were 11–64% lower. The eGFR explained 42–60% of L-Arg/SDMA, SDMA/ADMA, and SDMA variability (n = 38). Using linear regression, SDMA and SDMA/ADMA separately explained 15–38% of AW and AS systolic (S) BP and diastolic (D) BP load variability (p < 0.001–0.022). Using multivariate stepwise regression with eGFR held constant, SDMA/ADMA was a significant independent variable for AW DBP load (p = 0.03). In conclusion, BP load and a disproportionate elevation of SDMA are seen in children and adolescents with stage 2–3 (mild–moderate) CKD. SDMA is a strong marker for reduced eGFR and serves as a moderate but significant indicator of 24-hr BP load variability.

Fracture Burden and Risk Factors in Childhood CKD: Results from the CKiD Cohort Study

Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2- to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged ≥15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P≤0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, 0.15-0.91; P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P<0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.

Measurement of arginine derivatives in pediatric patients with chronic kidney disease using high-performance liquid chromatography-tandem mass spectrometry.

Abstract Background: The arginine derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) interfere with endothelial nitric oxide synthesis. Plasma ADMA and SDMA have been shown to be risk factors for cardiovascular disease and/or kidney function deterioration in a variety of patient populations. Methods: We developed a method to quantitatively measure arginine, ADMA, and SDMA using HPLC-tandem mass spectrometry. 13C6-L-Arginine was used as the internal standard, while the derivatives were separated on a silica column in less than 14 min. Plasma levels of ADMA, SDMA, and arginine were measured in children with stage II or III chronic kidney disease (CKD) and age- and gender-matched siblings. Results: The chromatography exhibited no observable ion suppression in the patient specimens tested. There was no apparent carryover for any of the analytes. The assay was linear over 0.32–2.29, 0.23–4.43, and 1.00–303.89 μmol/L for ADMA, SDMA, and arginine, respectively. Plasma ADMA, SDMA, and arginine (mean±SD) were 1.10±0.35, 2.06±1.11, and 57.93±22.10 μmol/L for children with CKD, and 0.78±0.16, 0.71±0.23, and 65.29±21.30 μmol/L for the healthy siblings. Conclusions: The method exhibited no observable ion suppression in the patient specimens tested and has an acceptably short analytical cycle time. Children with CKD had higher levels of ADMA and SDMA than the healthy siblings. Clin Chem Lab Med 2007;45:1305–12.

Bioelectric Impedance Predicts Total Body Water, Blood Pressure, and Heart Rate During Hemodialysis in Children and Adolescents

OBJECTIVE The purposes of our study were to: (1) assess if changes in the volemic status of children and adolescents over the course of standard dialysis could be observed using bioelectric impedance (BIA); and (2) evaluate whether the variability of blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP) and heart rate (HR) could be explained by independent variables from BIA data. DESIGN We used a randomized, single-blinded treatment and repeated-measures design. SETTING This study took place at the DaVita Childrens Dialysis Center (Chicago, IL). PATIENTS There were 7 subjects, aged 10 to 16 years. INTERVENTION Two identical standard hemodialysis (HD) sessions were completed, with data collected five times during each HD session: pre-HD, intra-HD (hours 1, 2, and 3), and post-HD. Endpoints included total body water (TBW), resistance (R), reactance (Xc), bioimpedance vector |Z|, supine and sitting SBP, DBP, and HR. Standing SBP, DBP, and HR were collected pre-HD and post-HD. RESULTS No differences were observed in TBW between HD sessions for all subjects. However, TBW decreased throughout the HD sessions for all subjects (although no significant differences were seen between hour 3 and post-HD). Reactance (representative of extracellular water) correlated with supine, sitting, and standing SBP (r = 0.55, 0.59, and 0.51, respectively; P < or = .008). The bioimpedance vector increased beginning at hour 1 (P < .001), reflective of a decline in tissue hydration over the course of HD. CONCLUSIONS Weight gain in end-stage kidney disease patients is largely fluid. Thus, the use of BIA during HD may aid in the prediction of cardiovascular instability before the development of symptoms, because intravascular hypovolemia and hypotension can result from excessive ultrafiltration below the critical dry weight. In addition, BIA explains, in part, the variability of SBP, DBP, and HR during HD. We suggest that our data also demonstrates the delay in mobilization of fluid from the interstitial space for plasma refill, as evidenced by the delayed change in |Z| over HD. Bioelectric impedance is useful for explaining changes in volemic status and, in part, the variability of SBP, DBP, and HR during HD.

Osteoporosis screening of postmenopausal women in the primary care setting : A case-based approach

BACKGROUND Despite the facts that approximately half of postmenopausal women will sustain an osteoporosis-related fracture and 15% will sustain a hip fracture in their lifetime, 75% of American women between the ages of 45 and 75 years have never discussed osteoporosis with their physician. OBJECTIVE This case-based review addresses screening for osteoporosis in the primary care setting. Topics include epidemiology, assessment of fracture risk, bone mineral density testing, primary prevention of osteoporosis, and thresholds for treatment. METHODS Relevant articles were identified through a search of MEDLINE (1980-2004) using the terms osteoporosis, fractures, randomized controlled trials (RCTs), and epidemiology, pathophysiology, diagnosis, and treatment of osteoporosis. Clinical guidelines on osteoporosis were also reviewed. CONCLUSIONS Osteoporosis is a prevalent disease in postmenopausal women. Osteoporosis-related fractures are a cause of major morbidity and mortality in older adults. Increased awareness of osteoporosis is necessary to stem the mounting number of complications.

Applicability of estimating glomerular filtration rate equations in pediatric patients: comparison with a measured glomerular filtration rate by iohexol clearance.

Estimating glomerular filtration rate (eGFR) has become popular in clinical medicine as an alternative to measured GFR (mGFR), but there are few studies comparing them in clinical practice. We determined mGFR by iohexol clearance in 81 consecutive children in routine practice and calculated eGFR from 14 standard equations using serum creatinine, cystatin C, and urea nitrogen that were collected at the time of the mGFR procedure. Nonparametric Wilcoxon test, Spearman correlation, Bland-Altman analysis, bias (median difference), and accuracy (P15, P30) were used to compare mGFR with eGFR. For the entire study group, the mGFR was 77.9 ± 38.8 mL/min/1.73 m(2). Eight of the 14 estimating equations demonstrated values without a significant difference from the mGFR value and demonstrated a lower bias in Bland-Altman analysis. Three of these 8 equations based on a combination of creatinine and cystatin C (Schwartz et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37; Schwartz et al. Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 2012;82:445-53; Chehade et al. New combined serum creatinine and cystatin C quadratic formula for GFR assessment in children. Clin J Am Soc Nephrol 2014;9:54-63) had the highest accuracy with approximately 60% of P15 and 80% of P30. In 10 patients with a single kidney, 7 with kidney transplant, and 11 additional children with short stature, values of the 3 equations had low bias and no significant difference when compared with mGFR. In conclusion, the 3 equations that used cystatin C, creatinine, and growth parameters performed in a superior manner over univariate equations based on either creatinine or cystatin C and also had good applicability in specific pediatric patients with single kidneys, those with a kidney transplant, and short stature. Thus, we suggest that eGFR calculations in pediatric clinical practice use only a multivariate equation.

Lateral Spine Densitometry in Obese Women

Abstract. The lateral (LAT) spine scan has been suggested as a more sensitive measure than posterior-anterior (PA) scanning for assessing age-related bone loss in normal-weight postmenopausal women. The measurement error of PA and LAT bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) has also been shown to rise with incremental increases in fat and from large variance in fat thickness, respectively. The purpose of this cross-sectional study was to determine specific affects of obesity on paired PA and LAT lumbar (L2–L4) BMD and Z score (BMD of patient versus age-matched reference database) correlation in 30 obese postmenopausal women (mean BMI ± SD = 33.3 ± 4.06). The mean PA and LAT BMD ± SD were 0.946 ± 0.123 and 0.749 ± 0.134, respectively. The mean PA and LAT Z scores were −0.17 ± 1.15 and 0.80 ± 1.7. The correlation between PA and LAT BMD was significantly lower (r = 0.55; P < 0.05) than previously reported, and PA and LAT Z score correlation was (r = 0.57; P= 0.0016). After adjusting for body mass index (BMI), percent body fat, fat mass, and truncal fat by DXA, waist:hip ratio (WHR) and visceral and subcutaneous abdominal fat by computerized axial tomography (CT), PA and LAT Z score correlation increased to r = 0.62; P= 0.0065. In our subjects, the mean LAT Z score was 4.6 times higher than the mean AP Z, contrary to previous observations in normal-weight postmenopausal women. Our findings may be due to increased soft tissue composition and fat inhomogeneity in the LAT scanning field resulting in increased X-ray attenuation in obesity.

Medication Adherence and Growth in Children with CKD

BACKGROUND AND OBJECTIVES Poor growth is a consequence of CKD, but can often be partially or fully prevented or corrected with the use of a number of medications. The extent of nonadherence with medications used to treat or mitigate growth failure in CKD has not been examined prospectively in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The prevalence of both prescription of and nonadherence to recombinant human growth hormone (rhGH), phosphate binders, alkali, active vitamin D, nutritional vitamin D, iron, and erythrocyte-stimulating agents was summarized over the first seven visits of the Chronic Kidney Disease in Children cohort study. The association between self-reported nonadherence to each medication group and the mean annual change in age- and sex-specific height z score was quantified using seven separate linear regression models with generalized estimating equations. RESULTS Of 834 participants, 597 reported use of at least one of these medication groups and had adherence data available. Nonadherence ranged from 4% over all visits for erythrocyte-stimulating agents to 22% over all visits for nutritional vitamin D. Of the study participants, 451 contributed data to at least one of the analyses of adherence and changes in height z score. Children nonadherent to rhGH had no change in height z score, whereas those adherent to rhGH had a significant improvement of 0.16 SDs (95% confidence interval, 0.05 to 0.27); the effect size was slightly larger and remained significant after adjustment. Among participants with height≤3rd percentile and after adjustment, adherence to rhGH was associated with a 0.33 SD (95% confidence interval, 0.10 to 0.56) greater change in height z score. Nonadherence with other medication groups was not significantly associated with a change in height z score. CONCLUSIONS Self-reported nonadherence to rhGH was associated with poorer growth velocity in children with CKD, suggesting an opportunity for intervention and improved patient outcome.