Bias and Accuracy of Glomerular Filtration Rate Estimating Equations in the US: A Systematic Review and Meta-Analysis.

Importance: There is increasing concern that continued use of a glomerular filtration rate (GFR) estimating equation adjusted for a single racial group could exacerbate chronic kidney disease-related disparities and inequalities. Objective: To assess the performance of GFR estimating equations across varied patient populations. Data Sources: PubMed, Embase, Web of Science, ClinicalTrials.gov, and Scopus databases were systematically searched from January 2012 to February 2023. Study Selection: Inclusion criteria were studies that compared measured GFR with estimated GFR in adults using established reference standards and methods. A total of 6663 studies were initially identified for screening and review. Data Extraction and Synthesis: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2 authors independently extracted data on studies that examined the bias and accuracy of GFR estimating equations. For each outcome, a random-effects model was used to calculate pooled estimates. Data analysis was conducted from March to December 2023. Main Outcomes and Measures: The primary outcomes were bias and accuracy of estimated GFRs in Black vs non-Black patients, as well as in individuals with chronic conditions. Bias was defined as the median difference between the measured GFR and the estimated GFR. Accuracy was assessed with P30 (the proportion of persons in a data set whose estimated GFR values were within 30% of measured GFR values) and measures of heterogeneity. Results: A total of 12 studies with a combined 44 721 patients were included. Significant heterogeneity was found in the bias of various GFR estimation equations. Race-corrected equations and creatinine-based equations tended to overestimate GFR in Black populations and showed mixed results in non-Black populations. For creatinine-based equations, the mean bias in subgroup analysis was 2.1 mL/min/1.73 m2 (95% CI, -0.2 mL/min/1.73 m2 to 4.4 mL/min/1.73 m2) in Black persons and 1.3 mL/min/1.73 m2 (95% CI, 0.0 mL/min/1.73 m2 to 2.5 mL/min/1.73 m2) in non-Black persons. Equations using only cystatin C had small biases. Regarding accuracy, heterogeneity was high in both groups. The overall P30 was 84.5% in Black persons and 87.8% in non-Black persons. Creatinine-based equations were more accurate in non-Black persons than in Black persons. For creatinine-cystatin C equations, the P30 was higher in non-Black persons. There was no significant P30 difference in cystatin C-only equations between the 2 groups. In patients with chronic conditions, P30 values were generally less than 85%, and the biases varied widely. Conclusions and Relevance: This systematic review and meta-analysis of GFR estimating equations suggests that there is bias in race-based GFR estimating equations, which exacerbates kidney disease disparities. Development of a GFR equation independent of race is a crucial starting point, but not the sole solution. Addressing the disproportionate burden of kidney failure on Black individuals in the US requires an enduring, multifaceted approach that should include improving diagnostics, tackling social determinants of health, confronting systemic racism, and using effective disease prevention and management strategies.

Training executive, attention, and motor skills: a proof-of-concept study in preschool children With ADHD.

OBJECTIVE: To examine whether cognitive enhancement can be delivered through play to preschoolers with ADHD and whether it would affect severity of ADHD symptoms. METHOD: Twenty-nine 4- and 5-year-old children and their parents participated in separate group sessions (3-5 children/group). Child groups were introduced games designed to enhance inhibitory control, working memory, attention, visuospatial abilities, planning, and motor skills. Parent groups were encouraged playing these games with their children at least 30 to 45 min/day and taught strategies for scaffolding difficulty levels and dealing with obstacles to daily playing. RESULTS: Parent ratings and session attendance indicated considerable satisfaction with the program. Parent (p < .001) and teacher (p = .003) ratings on the ADHD-Rating Scale-IV (ADHD-RS-IV) indicated significant improvement in ADHD severity from pre- to post-treatment, which persisted 3 months later. CONCLUSION: This play-based intervention for preschoolers with ADHD is readily implemented at home. Preliminary evidence suggests efficacy beyond the termination of active treatment.

Comparison of the impact of the I27L polymorphism of the hepatocyte nuclear factor-1alpha on estimated and measured beta cell indices.

OBJECTIVE: We investigated the impact of the I27L polymorphism of the hepatocyte nuclear factor-1alpha gene on measured and estimated beta cell indices. We also examined the conservation of this amino acid among different species. DESIGN AND METHODS: Estimated first and second phase insulin responses (1stPH(S) and 2ndPH(S)) were estimated from oral glucose tolerance tests in 78 glucose tolerant subjects. Among these subjects, first and second phase insulin responses (1stIR and 2ndIR) were measured in 60 subjects. The I27L genotypes were determined from genomic DNA. We also reviewed the published peptide sequence data on this polymorphism. RESULTS: The estimated beta cell indices correlated well with the measured indices. Although the impact of this polymorphism was noted in the measured indices (P<0.01 for 1stIR and P=0.04 for 2ndIR) from 60 subjects, the differences in the estimated indices were only noted in the extended sample set with 78 subjects (P=0.05 for 1stPH(S) and P=0.04 for 2ndPH(S)). This polymorphism occurs in the dimerization domain, which is completely conserved within human, rat, mouse and hamster. This amino acid is also conserved in chicken and zebrafish, but not in the frog. This conservation suggests a possible biological importance of this amino acid. CONCLUSIONS: By increasing the sample size, we demonstrated the role of the I27L polymorphism in the pathogenesis of type 2 diabetes by using estimated beta cell indices. The conservation among species suggests a possible biological importance of this amino acid. Analysis of the published data confirms a modest role of this polymorphism in type 2 diabetes.

Relative contribution of insulin sensitivity and beta-cell function to plasma glucose and insulin concentrations during the oral glucose tolerance test.

Plasma glucose and insulin concentrations have been used in genetic studies as quantitative phenotypic traits and also as surrogates for insulin sensitivity and beta-cell function. However, the significance of these traits in relation to insulin sensitivity and beta-cell function was unknown. We examined how insulin sensitivity and beta-cell function affected plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). This is a cross-sectional study enrolling 105 glucose-tolerant subjects (64 females; age, 18 to 40 years; body mass index, 17.58 to 37.57 kg/m(2); waist-to-hip ratio, 0.649 to 1.033 cm/cm). They participated in both OGTTs and hyperglycemic clamps. The relationship between plasma glucose and insulin concentrations and indices of insulin sensitivity and beta-cell function was examined. Univariate analyses showed that insulin sensitivity index (ISI) had some influence on plasma insulin concentrations (r(2) =.2623 to.3814) during the OGTT; however, it had only modest impacts on plasma glucose levels at 60, 90, and 120 minutes (r(2) =.0537 to.1300). Neither first phase (1stIR) nor second phase insulin response (2ndIR) affected plasma glucose concentrations. Multivariate analyses showed an independent impact (all P <.0001) of ISI on plasma glucose concentrations at 60, 90, and 120 minutes and on plasma insulin concentrations at every time point except at 30 minutes. Except for plasma insulin concentration at 30 minutes, of which 24% of the variation can be explained by 1stIR, beta-cell function (either 1stIR or 2ndIR) only had a very modest impact on 30-, 60-, 90- and 120-minute plasma glucose concentrations and on plasma insulin concentration at 60 minutes. In glucose-tolerant subjects, ISI plays an important role in determining postchallenged plasma glucose concentrations at 60, 90, and 120 minutes, as well as plasma insulin concentrations at fasting, 60, 90, and 120 minutes. However, beta-cell function is only reflected in plasma insulin concentration at 30 minutes through 1stIR. Therefore, we conclude that it is essential to measure beta-cell function in vivo if one plans to study the genetic influence of beta-cell dysfunction.