Differences in Creatinine- and Cystatin C-Based eGFR, Non-GFR Determinants, and Adverse Outcomes: A Population-Based Cohort Study

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Background: Increased use of cystatin C-based eGFR (eGFRcys), recommended when creatinine-based eGFR (eGFRcr) is inaccurate, means clinicians will increasingly encounter differences between these estimates. Lower eGFRcys than eGFRcr consistently associates with adverse outcomes, but whether this reflects non-GFR determinants of creatinine and cystatin C is unclear. Methods: We included 8,592 Dutch PREVEND study participants and derived eGFR using CKD-EPI and EKFC equations. Linear regression assessed associations of covariates with the difference between eGFRcr and eGFRcys (eGFRdiff). Proportional hazards models assessed associations of eGFRdiff with mortality, nonfatal cardiovascular events, and incident heart failure. Results: Higher muscle mass was associated with a greater eGFRcys relative to eGFRcr, while female sex, smoking, and higher body-mass index were associated with a lower eGFRcys relative to eGFRcr. Associations of a lower eGFRcys than eGFRcr with mortality and cardiovascular events were largely explained by cystatin C-related factors. In contrast, the association of a lower eGFRcys than eGFRcr with heart failure was largely independent of muscle mass and cystatin C-related factors (Figure). Conclusion: The association of eGFRdiff and heart failure was largely independent of non-GFR determinants. These findings support using eGFRdiff for early identification and preventive care in heart failure, providing rationale for cystatin C beyond confirmatory testing.Associations of CKD-EPI eGFRdiff with adverse outcomes. Shown are hazard ratios and 95% Bayesian credible intervals. The base model included age, sex, albuminuria, and eGFRdiff (eGFRcys – eGFRcr).

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