An optimal measurement of glomerular filtration rate (GFR) should minimize the number of blood draws, and reduce procedural invasiveness and the burden to study personnel and cost, without ...sacrificing accuracy. Equations have been proposed to calculate GFR from the slow compartment separately for adults and children. To develop a universal equation, we used 1347 GFR measurements from two diverse groups consisting of 527 men in the Multicenter AIDS Cohort Study and 514 children in the Chronic Kidney Disease in Children cohort. Both studies used nearly identical two-compartment (fast and slow) protocols to measure GFR. To estimate the fast component from markers of body size and of the slow component, we used standard linear regression methods with the log-transformed fast area as the dependent variable. The fast area could be accurately estimated from body surface area by a simple parameter (6.4/body surface area) with no residual dependence on the slow area or other markers of body size. Our equation measures only the slow iohexol plasma disappearance curve with as few as two time points and was normalized to 1.73m2 body surface area. It is of the form: GFR=slowGFR/1+0.12(slowGFR/100). In a random sample utilizing a third of the patients for validation, there was excellent agreement between the calculated and measured GFR with low root mean square errors being 4.6 and 1.5ml/min per 1.73m2 for adults and children, respectively. Thus, our proposed simple equation, developed in a combined patient group with a broad range of GFRs, may be applied universally and is independent of the injected amount of iohexol.
The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the ...study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD’s contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.
OBJECTIVE:The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body ...composition among adult men with HIV and without HIV.
DESIGN/METHODS:Men with and without HIV (age 50–69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition.
RESULTS:A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20).
CONCLUSION:Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting.
OBJECTIVES:The aim of this study was to determine cardiac arrest– and extracorporeal membrane oxygenation–related risk factors associated with unfavorable outcomes after extracorporeal ...cardiopulmonary resuscitation.
DESIGN:We performed an analysis of merged data from the Extracorporeal Life Support Organization and the American Heart Association Get With the Guidelines—Resuscitation registries.
SETTING:A total of 32 hospitals reporting to both registries between 2000 and 2014.
PATIENTS:Children younger than 18 years old who suffered in-hospital cardiac arrest and underwent extracorporeal cardiopulmonary resuscitation.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Of the 593 children included in the final cohort, 240 (40.5%) died prior to decannulation from extracorporeal membrane oxygenation and 352 (59.4%) died prior to hospital discharge. A noncardiac diagnosis and preexisting renal insufficiency were associated with increased odds of death (adjusted odds ratio, 1.85 95% CI, 1.19–2.89 and 4.74 95% CI, 2.06–10.9, respectively). The median time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation was 48 minutes (interquartile range, 28–70 min). Longer time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation was associated with higher odds of death prior to hospital discharge (adjusted odds ratio for each 5 additional minutes of cardiopulmonary resuscitation prior to extracorporeal membrane oxygenation initiation, 1.04 95% CI, 1.01–1.07). Each individual adverse event documented during the extracorporeal membrane oxygenation course, including neurologic, pulmonary, renal, metabolic, cardiovascular and hemorrhagic, was associated with higher odds of death, with higher odds as the cumulative number of documented adverse events during the extracorporeal membrane oxygenation course increased.
CONCLUSIONS:Outcomes after extracorporeal cardiopulmonary resuscitation reported by linking two national registries are encouraging. Noncardiac diagnoses, preexisting renal insufficiency, longer time from onset of the cardiopulmonary resuscitation event to extracorporeal membrane oxygenation initiation, and adverse events during the extracorporeal membrane oxygenation course are associated with worse outcomes.
To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD.
Observational cohort study.
...Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data.
Neighborhood poverty and neighborhood disadvantage.
Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy KRT or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis.
Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income.
There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 95% CI, 1.08-2.71) and ED use (OR, 1.56 95% CI, 1.02-2.40) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 95% CI, 1.02-1.87). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 95% CI, 0.24-0.96) and higher neighborhood deprivation (OR, 0.31 95% CI, 0.10-0.97), but these associations did not persist after controlling for participant characteristics.
Limited generalizability, as only those with consistent longitudinal nephrology care were studied.
Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.
•Algorithms had lower sensitivity for classification of incident versus prevalent dementia.•97.5% or lower specificity led to bias towards the null in time-to-event analyses.•Differential performance ...by exposure status can lead to bias in any direction.•Researchers should consider study goals in algorithm development.
Dementia algorithms are often developed in cross-sectional samples but implemented in longitudinal studies to ascertain incident dementia. However, algorithm performance may be higher in cross-sectional settings, and this may impact estimates of risk factor associations.
We used data from the Religious Orders Study and the Memory and Aging Project (N = 3460) to assess the performance of example algorithms in classifying prevalent dementia in cross-sectional samples versus incident dementia in longitudinal samples. We used an applied example and simulation study to characterize the impact of varying sensitivity, specificity, and unequal sensitivity or specificity between exposure groups (differential performance) on estimated hazard ratios from Cox models.
Using all items, algorithm sensitivity was higher for prevalent (0.796) versus incident dementia (0.719); hazard ratios had slight bias. Sensitivity differences were larger using a subset of items (0.732 vs. 0.600) and hazard ratios were 13%–19% higher across adjustment sets compared to estimates using gold-standard dementia status. Simulations indicated specificity and differential algorithmic performance between exposure groups may have large effects on hazard ratios.
Algorithms developed using cross-sectional data may be adequate for longitudinal settings when performance is high and non-differential. Poor specificity or differential performance between exposure groups may lead to biases.
Aims
There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose–response in paediatric extracorporeal membrane oxygenation (ECMO) patients.
...Methods
We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post‐ vs. pre‐AT replacement were compared in order to characterize a dose–response relationship.
Results
The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range IQR, 51–82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5–67.2) and 23.5% (IQR, 9.8–36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion. There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols.
Conclusions
There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes. Further data are needed to identify optimal dosing strategies.
Background:
Ambulatory blood pressure monitoring (ABPM) is routinely performed in children with chronic kidney disease to identify masked hypertension, a risk factor for accelerated chronic kidney ...disease progression. However, ABPM is burdensome, and developing an accurate prediction of masked hypertension may allow using ABPM selectively rather than routinely.
Methods:
To create a prediction model for masked hypertension using clinic blood pressure (BP) and other clinical characteristics, we analyzed 809 ABPM studies with nonhypertensive clinic BP among the participants of the Chronic Kidney Disease in Children study.
Results:
Masked hypertension was identified in 170 (21.0%) observations. We created prediction models for masked hypertension via gradient boosting, random forests, and logistic regression using 109 candidate predictors and evaluated its performance using bootstrap validation. The models showed
C
statistics from 0.660 (95% CI, 0.595–0.707) to 0.732 (95% CI, 0.695–0.786) and Brier scores from 0.148 (95% CI, 0.141–0.154) to 0.167 (95% CI, 0.152–0.183). Using the possible thresholds identified from this model, we stratified the dataset by clinic systolic/diastolic BP percentiles. The prevalence of masked hypertension was the lowest (4.8%) when clinic systolic/diastolic BP were both <20th percentile, and relatively low (9.0%) with clinic systolic BP<20th and diastolic BP<80th percentiles. Above these thresholds, the prevalence was higher with no discernable pattern.
Conclusions:
ABPM could be used selectively in those with low clinic BP, for example, systolic BP<20th and diastolic BP<80th percentiles, although careful assessment is warranted as masked hypertension was not completely absent even in this subgroup. Above these clinic BP levels, routine ABPM remains recommended.
Objective
Persistent organic pollutants (POPs) are lipophilic environmental toxicants that accumulate in adipose tissue. Weight loss leads to mobilization and increased redistribution of these ...toxicants. Many are obesogens and endocrine disruptors. Increased exposure could pose long‐term health risks. The study objective was to measure the changes in serum concentrations of lipophilic POPs during significant weight loss.
Methods
This study enrolled 27 patients at a university hospital in a longitudinal, 6‐month, observational study examining changes in POP blood levels after bariatric surgery. The primary outcome was the changes in the concentrations of 24 polychlorinated biphenyls (PCBs), 9 organochlorine pesticides (OCPs), 11 polybrominated diphenyl ethers, 2,2′,4,4′,5,5′‐hexabromobiphenyl, and 4 perfluorochemicals (PFCs).
Results
Older adults (those born before 1976) had baseline levels of PCBs, OCPs, and PFCs that were two‐ to fivefold higher than younger adults (those born after 1976). Older adults had greater increases in PCBs, OCPs, and polybrominated diphenyl ethers associated with weight loss. Conversely, younger adults had greater increases in PFCs associated with weight loss. On average, blood POP levels increased as weight loss occurred.
Conclusions
Although weight loss is considered beneficial, the release and redistribution of POPs to other lipid‐rich organs such as the brain, kidneys, and liver warrant further investigation. Interventions should be considered to limit organ exposure to POPs when weight loss interventions are planned.
Background
Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what clinic blood pressure (BP) levels may slow progression.
...Methods
Longitudinal BP data from children in the Chronic Kidney Disease in Children cohort study who had hypertension or an auscultatory BP ≥ 90th percentile were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (< 50th, 50th to 75th, 75th to 90th, and ≥ 90th percentile) with time-updated classifications corresponding to annual study visits. The primary outcome was time to kidney replacement therapy or a 30% decline in estimated glomerular filtration rate. Cox proportional hazard models described the effect of each BP category compared to BP ≥ 90th percentile.
Results
Seven hundred fifty-four participants (median age 9.9 years at study entry) met inclusion criteria; 65% were male and 26% had glomerular CKD. Any BP < 90th percentile was associated with a decreased risk of progression for those with glomerular CKD (hazard ratio (HR), 0.63; 95% CI, 0.28–1.39 (< 50th); HR, 0.59; 95% CI, 0.28–1.26 (50th–75th); HR, 0.40; 95% CI, 0.18–0.93 (75th–90th)). Similar results were found for those with non-glomerular CKD: any BP < 90th percentile was associated with decreased risk of progression (HR, 0.78; 90% CI, 0.49–1.25 (< 50th); HR, 0.53; 95% CI, 0.33–0.84 (50th–75th); HR, 0.71; 95% CI, 0.46–1.08 (75th–90th)).
Conclusions
Achieved clinic BP < 90th percentile was associated with slower CKD progression in children with glomerular or non-glomerular CKD. These data provide guidance for management of children with CKD in the office setting.
Graphical abstract
PDF
