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Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results

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Abstract

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.

Graphical Abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

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Data availability

Data from the Chronic Kidney Disease in Children cohort study [(V7)/https://doi.org/10.58020/dzq8-ct80] are available for request at the NIDDK Central Repository (NIDDK-CR) website, Resources for Research (R4R), https://repository.niddk.nih.gov/.

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Acknowledgements

Data in this manuscript were collected by the Chronic Kidney Disease in Children (CKiD) prospective cohort study with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri – Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (Jesse Seegmiller, PhD) at the University of Minnesota, and data coordinating center (Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD study is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01 DK066143, U01 DK066174, U24 DK137522, U24 DK066116). The CKiD website is located at https://statepi.jhsph.edu/ckid and a list of CKiD collaborators can be found in the Supplementary Material and at https://statepi.jhsph.edu/ckid/site-investigators/.

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  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Room E7642, Baltimore, MD, 21205, USA

    Derek K. Ng & Alvaro Muñoz

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Correspondence to Derek K. Ng.

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Ng, D.K., Muñoz, A. & for the CKiD Study Investigators. Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results. Pediatr Nephrol (2024). https://doi.org/10.1007/s00467-024-06318-4

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