Reply: Comment on “Kidney Function and Incident Stroke and Dementia Using an Updated Estimated Glomerular Filtration Rate Equation Without Race: The Multi-Ethnic Study of Atherosclerosis”

To the Editor:

We appreciate Dr Williams’s commentary and the opportunity to respond. The comments focus on race-free eGFR based solely on serum creatinine (eGFRcr) level, disregarding the utility of measuring cystatin C alongside creatinine, which provides greater accuracy and equity.¹

Dr Williams suggests that Table S5 challenges the utility of race-free eGFRcr reclassification, suggesting that the race-based equation better demonstrates risk. Table S5 includes small sample sizes and a limited number of events. It is descriptive in nature and was not intended to be interpreted as conclusive evidence of eGFR equation performance. In addition, in most referred comparisons, the 95% confidence intervals overlap, limiting interpretation and comparisons.

Williams also suggests that the higher hazard ratios observed in Table 3 using the race-based eGFRcr equation might reflect its greater accuracy. The attenuation of hazard ratios are related to reclassification, not misclassification. Race-free eGFRcr reclassified 52 participants from eGFR 60-90 to <60 mL/min/1.73 m², increasing the total from 99 to 151. These additional participants are at the border of the eGFR <60 cutoff and likely carry a lower risk of events than participants who were already included in the category, considering it is not a homogeneous group with respect to risk. Reclassification adds relatively fewer events and thus results in a lower hazard ratio.²

Finally, reclassification occurred in both directions. Our study highlighted the longstanding underrecognition of kidney disease in African American individuals under the race-based eGFR formulas.³ Future research should continue investigating methods that integrate eGFR with clinical context rather than adhering to rigid thresholds.