Cystatin C- and creatinine-based estimated GFR differences: prevalence and predictors in the UK Biobank

Chen, D. C. et al. (2024) Cystatin C- and creatinine-based estimated GFR differences: prevalence and predictors in the UK Biobank. Kidney Medicine, 6(4), 100796. (doi: 10.1016/j.xkme.2024.100796) (PMID:8567244) (PMCID:PMC10986041)

Abstract

Rationale & objective: Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values. Study design: Cohort study. Setting & participants: 468,969 participants in the UK Biobank. Exposures: Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors. Outcomes: eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2). Analytical approach: Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants. Results: Mean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00). Limitations: Limited generalizability. Conclusions: This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

• Item Type: Articles
• Additional Information: Dr Chen was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant F32DK130543. Drs Shlipak and Estrella are supported by SD-20-387 from the Department of Veterans Affairs. Dr Potok is supported by American Kidney Fund Clinical Scientist in Nephrology Fellow program; Akebia Therapeutics, Inc; and National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK128604. Dr Rifkin is supported by VA Merit Award HSRandD IIR 15-369.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mark, Professor Patrick and Lees, Jennifer and Rutherford, Dr Elaine
• Authors: Chen, D. C., Lu, K., Scherzer, R., Lees, J. S., Rutherford, E., Mark, P. B., Potok, O. A., Rifkin, D. E., Ix, J. H., Shlipak, M. G., and Estrella, M. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Kidney Medicine
• Publisher: Elsevier
• ISSN: 2590-0595
• Published Online: 16 February 2024
• Copyright Holders: Copyright © 2024 Elsevier
• First Published: First published in Kidney Medicine 6(4):100796
• Publisher Policy: Reproduced under a Creative Commons licence