Search

Background: Assessing bias (estimated – measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. Methods: Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. Results: A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (–12.2%; 95%CI − 17.3%, − 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and − 1.0%, respectively) congruent with strong agreement. Conclusions: Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases. [ABSTRACT FROM AUTHOR]

Quality control in longitudinal cohort studies is critical for valid epidemiologic inference. Conditional studentized residuals (CSRs) derived from linear mixed effects models offer efficient individual-specific quality control. We present the utility of CSRs for outlier detection in an applied example using data from the Chronic Kidney Disease in Children cohort. Longitudinal linear mixed effects models with glomerular filtration rate (GFR) as the outcome were fit for observations prior to kidney replacement therapy, stratified by nonglomerular or glomerular diagnosis, and for a subset after receiving a kidney transplant. For each model, CSRs were calculated and values ≥±5 were considered potential outliers for further investigation. A total of 1096 participants contributed 6881 annual measures of GFR across the two diagnostic groups and after transplant. In all models, the fixed effects captured progressive GFR decline. CSRs provided measures of individual-level deviations from the modeled trajectories (random + fixed effects) and were easily visualized in longitudinal plots. A total of 38 potential outliers from 32 participants were detected and further investigated for quality control. This example demonstrated how longitudinal models can provide CSRs to detect individual-specific outliers. CSRs should be considered as part of quality control for longitudinal epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with many comorbidities requiring complex management. We described treatment patterns for common modifiable CKD complications (high blood pressure, anemia, hyperphosphatemia, and acidosis) according to severity of CKD and examined factors associated with the absence of drug therapy, among participants with a persistent comorbidity, for 1 year in children enrolled in the CKiD study. Methods: A total of 703 CKiD participants contributed 2849 person-visits over a median 3.5 years of follow-up. Using pairs of annual visits, we examined whether participants with abnormal biomarker levels at the first (index) visit persisted in the abnormal levels 1 year later according to CKD risk stage. Multivariate analyses identified demographic and clinical factors associated with the absence of drug therapy among those with persistent comorbid conditions for 1 year. Results: The overall proportions of person-visits prescribing therapy at 1-year follow-up for treating anemia, acidosis, hyperphosphatemia, and high blood pressure were 54%, 45%, 29%, and 81%, respectively. The frequency of therapy increased with advanced CKD risk stage for all comorbidities; however, 19–23% of participants with acidosis, 24–27% with anemia, and 30–39% with hyperphosphatemia at high-risk stages (E and F) were not prescribed appropriate therapy despite the persistence of abnormal levels of these biomarkers for at least 1 year. The resolution of comorbidities at advanced CKD stages without treatment was unlikely. Conclusions: Many children with CKD in the CKiD cohort did not receive pharmacological treatment for common and persistent modifiable comorbidities, even in severe CKD risk stages. [ABSTRACT FROM AUTHOR]

Background: We investigated the putative associations of alcohol, cigarette, e-cigarette, and marijuana use with kidney function and proteinuria among adolescents and young adults (AYA) with pediatric-onset chronic kidney disease (CKD) enrolled in the Chronic Kidney Disease in Children (CKiD) study. Methods: Participants responded to questions about past year and 30-day substance use. Associations between each substance and kidney function, proteinuria, nephrotic range proteinuria, and high blood pressure were separately estimated using repeated measures regression models, adjusting for sociodemographic characteristics. Models controlled for covariates at the present visit (contemporaneous) and additionally controlled for disease severity at the year prior to reporting substance use (lagged). Results: A total of 441 participants ≥16 years contributed 1,245 person-visits with 39% reporting alcohol and 16%, 17%, and 15% reporting cigarette, e-cigarette, and marijuana use, respectively, over the previous year. In adjusted lagged models, past year and 30-day cigarette use were significantly associated with higher levels of proteinuria (+18.6%, 95%CI: +2.8%, +36.9%; and +20.0%, 95%CI: +0.7%, +43.1%, respectively). Inferences were similar when controlling for secondhand smoke exposure. Conclusions: In a cohort of AYA with pediatric kidney diseases, substance use was non-trivial, and cigarette use was associated with higher proteinuria, although the prevalence of use was low. Occasional alcohol, e-cigarette, and marijuana use were not associated with proteinuria, disease progression, or elevated blood pressure. Pediatric nephrologists as specialty care providers are well-positioned to discuss substance use and should encourage tobacco prevention/treatment efforts among AYA at high risk for use in order to preserve kidney function and promote well-being. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

The Chronic Kidney Disease in Children Study, a prospective cohort study with data collected from 2003 to 2018, provided the first opportunity to characterize the incidence of renal replacement therapy (RRT) initiation over the life course of pediatric kidney diseases. In the current analysis, parametric generalized gamma models were fitted and extrapolated for RRT overall and by specific treatment modality (dialysis or preemptive kidney transplant). Children were stratified by type of diagnosis: nonglomerular (mostly congenital; n  = 650), glomerular–hemolytic uremic syndrome (HUS; n  = 49), or glomerular–non-HUS (heterogeneous childhood onset; n  = 216). Estimated durations of time to RRT after disease onset for 99% of the nonglomerular and glomerular–non-HUS groups were 42.5 years (95% confidence interval (CI): 31.0, 54.1) and 25.4 years (95% CI: 14.9, 36.0), respectively. Since onset for the great majority of children in the nonglomerular group was congenital, disease duration equated with age. A simulation-based estimate of age at RRT for 99% of the glomerular population was 37.9 years (95% CI: 33.6, 63.2). These models performed well in cross-validation. Children with glomerular disease received dialysis earlier and were less likely to have a preemptive kidney transplant, while the timing and proportions of dialysis and transplantation were similar for the nonglomerular group. These diagnosis-specific estimates provide insight into patient-centered prognostic information and can assist in RRT planning efforts for children with moderate-to-severe kidney disease who are receiving regular specialty care. [ABSTRACT FROM AUTHOR]

Purpose: Coefficients of determination (R2) 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 (R2) 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 R2 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 R2 divulged different disease processes by risk factor and diagnoses. Among children with glomerular CKD, time-varying R2 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 R2 for each risk factor was not substantially different from time-constant estimates.Conclusions: Proteinuria and FGF23 explained substantial eGFR variability over time. Time-varying R2 can characterize predictive roles of risk factors on disease progression, overcome limitations of time-constant estimates, and are easily derived from mixed effects models. [ABSTRACT FROM AUTHOR]

Purpose: Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. Materials and Methods: The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m2. Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Results: Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m2. Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m2 (bias = −0.5, 95% CI −1.7 to 0.7, p = 0.44). Conclusions: Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured glomerular filtration rate in this population. [Copyright &y& Elsevier]