Effect of Creatinine Analytic and Biological Variation on Classification of Chronic Kidney Disease Stages using the CKD-EPI 2021 eGFR Equation
Date:
Background: In 2021 the equation to estimate glomerular filtration rate (eGFR) was modified to remove the race variable as it is a social and not a biologic construct (NEJM 2021). Prevalence of chronic kidney disease (CKD) among black adults was reported to increase by 3.5% with the removal of race from the equation (JAMA 2021). This is the first of a series of descriptive studies investigating factors contributing to variation in eGFR results. In this study, the contribution of creatinine analytic and biologic variation (BV) on the classification of Kidney Disease in Global Outcome (KDIGO) CKD stages using the CKD-EPI 2021 eGFR equation was assessed. Methods: Statistical bootstrapping of CDC-NHANES 2017-18 data (n= 6401?) was used to generate our study population of eGFR variables prior to the introduction of creatinine analytic (bias and imprecision) and BV. The impact of this variation on the sensitivity and specificity of KDIGO single eGFR thresholds and the actual CKD stage categorization was assessed.
Results: With no analytic or BV, the sensitivity and specificity at the 60 and 30 ml/min/m2 eGFR thresholds were both > 99%. Sensitivity and specificity estimates accounting for a creatinine within person BV of 4.5% were > 90% and > 99% respectively at both the 60 and 30 ml/min/m2 thresholds. The inclusion of -10% bias with the 4.5% BV resulted in sensitivity and specificity estimates of 63% and >99% (60 ml/min/m2) and 74% and >99% (30 ml/min/m2), respectively. Up to 3% of eGFR results were recategorized into different KDIGO CKD stages with combinations of creatinine analytic and BV.
Conclusions: Creatinine analytic and BV can introduce significant variation in calculated eGFR results thereby affecting the calculated sensitivity and specificity at the KDIGO single eGFR thresholds.