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

Abstract

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 44721 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 m2to 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 P30was 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 P30was higher in non-Black persons. There was no significant P30difference in cystatin C-only equations between the 2 groups. In patients with chronic conditions, P30values 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.