Association of Urinary EGF with Kidney Outcomes and Effects of Sodium-Glucose Cotransporter 2 Inhibition.
Erik Moedt, Akihiko Koshino, Niels Jongs et al.
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In 30 seconds
This analysis of stored urine samples from participants in three randomized clinical trials examined urinary EGF-to-creatinine ratio (uEGF/Cr) as a marker of tubular health and kidney risk across CKD populations, with and without type 2 diabetes. Higher baseline uEGF/Cr was associated with lower risk of a composite kidney outcome; in CANVAS and CREDENCE, the hazard ratio per two-fold higher uEGF/Cr was 0.87 (95% confidence interval, 0.80 to 0.94). Compared with placebo, SGLT2 inhibition attenuated the 1-year decline in uEGF/Cr by 6.7% (95% confidence interval, 2.5 to 10.8).
Key findings
- In CANVAS and CREDENCE participants with type 2 diabetes, each two-fold higher baseline uEGF/Cr was associated with lower composite kidney-outcome risk (hazard ratio, 0.87; 95% confidence interval, 0.80 to 0.94).
- SGLT2 inhibitors attenuated the 1-year uEGF/Cr decline versus placebo by 6.7% (95% confidence interval, 2.5 to 10.8).
- A 1-year increase in uEGF/Cr was associated with lower kidney-outcome risk independently of changes in albuminuria, eGFR, and other clinical variables.
- DAPA-CKD replication analyses showed similar findings in participants with and without diabetes.
Why it matters
The findings support uEGF/Cr as a marker of tubular health that is associated with kidney risk across varied CKD populations. Its association with outcomes beyond changes in albuminuria and eGFR suggests it may provide complementary prognostic information. The observed response to SGLT2 inhibition also links treatment exposure with preservation of this biomarker, although the results do not establish that biomarker changes mediate clinical benefit.
What to keep in mind
The analyses used stored urine samples from existing trials, and the reported biomarker associations do not establish that changes in uEGF/Cr cause changes in kidney outcomes.