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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.

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.

Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.Observational cohort study.Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively.Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status.mGFR based on iohexol clearance.Linear regression with generalized estimating equations, stratified by age (6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations.Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups.Small number of children 6 years; lean body mass was estimated.Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses.We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models.People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates.Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Purpose Coefficients of determination (R 2 ) for continuous longitudinal data are typically reported as time constant, if they are reported at all. The widely used mixed model with random intercepts and slopes yields the total outcome variance as a time-varying function. We propose a generalized and intuitive approach based on this variance function to estimate the time-varying predictive power (R 2 ) of a variable on outcome levels and changes. Methods Using longitudinal estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease in Children Study, linear mixed models characterized the R 2 for two chronic kidney disease (CKD) risk factors measured at baseline: a traditional marker (proteinuria) and a novel marker (fibroblast growth factor 23 [FGF23]). Results Time-varying R 2 divulged different disease processes by risk factor and diagnoses. Among children with glomerular CKD, time-varying R 2 for proteinuria had significant upward trends, suggesting increasing power to predict eGFR change, but crossed with FGF23, which was higher up to 2.5 years from baseline. In contrast, among those with nonglomerular CKD, proteinuria explained more than FGF23 at all times, and time-varying R 2 for each risk factor was not substantially different from time-constant estimates. Conclusions Proteinuria and FGF23 explained substantial eGFR variability over time. Time-varying R 2 can characterize predictive roles of risk factors on disease progression, overcome limitations of time-constant estimates, and are easily derived from mixed effects models.

As patients with chronic kidney disease (CKD) transition from pediatric nephrology care to adult care, their kidney function is clinically assessed by estimated glomerular filtration rate (eGFR) using both pediatric and adult equations, which may not be congruent. Here we evaluated commonly used eGFR equations and directly measured iohexol GFR (iGFR) among participants between ages 18 and 26 with a diagnosis of pediatric CKD in the Chronic Kidney Disease in Children (CKiD) cohort. The bedside serum creatinine (SCr) only equation (CKiD(SCr)), the SCr-only CKD-EPI (CKD-EPI(SCr)), the cystatin C (Cys)-only CKD-EPI (CKD-EPI(Cys)) and the combined SCr and Cys CKD-EPI (CKD-EPI(SCr-Cys)) were compared with a) 279 measured iGFRs obtained from 187 participants and b) 548 eGFRs from the SCr and Cys-based CKiD equation (CKiD(SCr-Cys)) obtained from 219 participants. Among emerging adults with a median iGFR of 49 ml/min|1.73m(2), the CKiD(SCr-Cys) equation had low bias (+1.5 ml/min|1.73m(2)) and high correlation (0.94), while CKiD(SCr) underestimated iGFR and CKiD(SCr-Cys) (-5.6 and −7.4 ml/min|1.73m(2), respectively) and CKD-EPI(SCr) had an overestimation bias (+8.2 and +6.1 ml/min|1.73m(2), respectively). However, the CKD-EPI(Cys) and CKD-EPI(SCr-Cys) exhibited strong agreement with both iGFR and CKiD(SCr-Cys). GFR may also be validly estimated in this population by taking the simple average of CKiD(SCr) and CKD-EPI(SCr) (average bias +1.3 compared to iGFR and −0.6 compared to CKiD(SCr-Cys)). Clinicians should be aware that individually the pediatric and adult SCr-based estimates of GFR had large discrepancies among emerging adults with pediatric CKD. Thus, when cystatin C is not available, we recommend the average of pediatric and adult SCr-based eGFR as a valid tool for clinical use.

Objective To describe the prevalence of obesity as estimated by waist circumference (WC) and body mass index (BMI) and compare associations of WC and BMI with indicators of metabolic, cardiovascular, and renal health in children with chronic kidney disease (CKD). Study design Cross-sectional analysis stratified by CKD etiology (nonglomerular or glomerular) of 737 subjects. The kappa statistic was used to assess agreement between the 2 measures of obesity. Linear regression models were performed using WC and BMI as separate independent variables. Dependent variables included lipid measures, insulin resistance, blood pressure, left ventricular mass index, proteinuria, and estimated glomerular filtration rate. Associations were scaled to SD and interpreted as the change in dependent variable associated with a 1-SD change in WC or BMI. Results There was good agreement (kappa statistic = 0.68) between WC and BMI in identifying obesity. Approximately 10% of subjects had obesity by 1 measure but not the other. BMI was more strongly associated with estimated glomerular filtration rate than WC. BMI was more strongly associated with left ventricular mass index in the nonglomerular CKD group compared with WC, but both had significant associations. The associations between WC and BMI with the remainder of the dependent variables were not significantly different. Conclusions Measurement of WC added limited information to BMI in this cohort. Further longitudinal study is needed to determine how WC and BMI compare in predicting outcomes, particularly for children with CKD identified as having obesity by 1 measure but not the other.

Background 2 valid and reliable estimated glomerular filtration rate (GFR) equations for the pediatric population have been developed from directly measured GFR data in the Chronic Kidney Disease in Children (CKiD) cohort: the full CKiD and bedside CKiD equations. Although adult GFR estimating equations replicate relationships of measured GFR with biomarkers, it is unclear whether similar patterns exist among children and adolescents with chronic kidney disease (CKD). Study Design Prospective cohort study in children and adolescents. Settings & Participants 730 participants contributed 1,539 study visits. Predictors Measured GFR by plasma iohexol disappearance (mGFR), estimated GFR by the full CKiD equation (eGFR CKiDfull ; based on serum creatinine, cystatin C, serum urea nitrogen, height, and sex), and estimated GFR by the bedside CKiD equation (eGFR CKiDbed ; calculated as 41.3 × height [m]/serum creatinine [mg/dL]) were predictors of CKD-related biomarkers. Deviations of mGFR from eGFR CKiDfull and deviations of eGFR CKiDfull from eGFR CKiDbed from linear regressions (ie, residuals) were included in bivariate analyses. Outcomes & Measurements: CKD-related biomarkers included values for urine protein-creatinine ratio, blood hemoglobin, serum phosphate, bicarbonate, potassium, systolic and diastolic blood pressure z scores, and height z scores. Results The median age of 730 participants with CKD was 12.5 years, with median mGFR, eGFR CKiDfull , and eGFR CKiDbed of 51.8, 54.0, and 53.2mL/min/1.73m 2 , respectively. eGFR CKiDfull demonstrated as strong or stronger associations with CKD-related biomarkers than mGFR; eGFR CKiDbed associations were significantly attenuated (ie, closer to the null). Residual information in mGFR did not substantially increase explained variability. eGFR CKiDbed estimated faster GFR decline relative to mGFR and eGFR CKiDfull . Limitations Simple linear summaries of biomarkers may not capture nonlinear associations. Conclusions eGFR CKiDfull closely approximated mGFR to describe relationships with CKD-severity indicators and progression in this pediatric CKD population. eGFR CKiDbed offered similar inferences, but associations were attenuated and rate of progression was overestimated. The eGFR CKiDfull equation from 2012 is preferred for pediatric research purposes.

Background Among adults, lower socioeconomic status (SES) is a risk factor for chronic kidney disease (CKD), progression to end-stage renal disease, and poor health outcomes; but its impact on young people with CKD is not established. Study Design Prospective cohort study. Settings & Participants 572 children and adolescents aged 1-16 years with mild to moderate CKD residing in the United States and Canada who were enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Predictor Self-reported annual household income category as a proxy measure for SES: ≥$75,000 (high income), $30,000 to Outcomes & Measurements Clinical characteristics and CKD severity at baseline (glomerular filtration rate [GFR] and comorbid conditions related to disease severity and management) and longitudinally (GFR decline and changes in blood pressure z scores and height z scores per year). Results At baseline, low and middle household incomes, compared to high income, were associated with minority race (39% and 20% vs 7%), lower maternal education (28% and 5% vs 1%), abnormal birth history (34% and 32% vs 21%), and having at least one clinical comorbid condition (66% and 64% vs 55%). Baseline median GFRs were similar across income categories (43-45 mL/min/1.73 m 2 ). After adjusting for baseline differences, average GFR declines per year for the low-, middle-, and high-income categories were −2.3%, −2.7%, and −1.9%, respectively, and were not statistically significantly different among groups. Blood pressure control tended to improve in all groups ( z score, −0.10 to −0.04) but higher income was associated with a faster improvement. Each group showed similar deficits in height at baseline. Height deficits diminished over time for participants from high-income families, but not among those from low-income families (z scores for height per year, 0.05 and −0.004, respectively; P = 0.03 for comparison of high and low income). Limitations Income is an imperfect measure for SES; CKiD participants are not representative of children and adolescents with CKD who are uninsured or not receiving care; statistical power to detect associations by income level is limited. Conclusions GFR decline was similar across income groups but better improvement in BP was observed among those with high income. Children and adolescents with CKD from lower income households are at higher risk of impaired growth.

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 1.73m 2 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 1.73m 2 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.

To examine the associations between abnormal birth history (birth weight2500 g, gestational age36 weeks, or small for gestational age), blood pressure (BP), and renal function among 332 participants (97 with abnormal and 235 with normal birth history) in the Chronic Kidney Disease in Children Study, a cohort of children with chronic kidney disease (CKD).Casual and 24-hour ambulatory BP were obtained. Glomerular filtration rate (GFR) was determined by iohexol disappearance. Confounders (birth and maternal characteristics, socioeconomic status) were used to generate predicted probabilities of abnormal birth history for propensity score matching. Weighted linear and logistic regression models with adjustment for quintiles of propensity scores and CKD diagnosis were used to assess the impact of birth history on BP and GFR.Age at enrollment, percent with glomerular disease, and baseline GFR were similar between the groups. Those with abnormal birth history were more likely to be female, of Black race or Hispanic ethnicity, to have low household income, or part of a multiple birth. Unadjusted BP measurements, baseline GFR, and change in GFR did not differ significantly between the groups; no differences were seen after adjusting for confounders by propensity score matching.Abnormal birth history does not appear to have exerted a significant influence on BP or GFR in this cohort of children with CKD. The absence of an observed association is likely secondary to the dominant effects of underlying CKD and its treatment.