Creatinine-based eGFR is shaped by how much creatinine a person makes, not only by how well their kidneys clear it. This editorial highlights a newly identified African-ancestry-specific variant at the GATM locus, which encodes glycine amidinotransferase in the creatine synthesis pathway.

The variant increases creatine synthesis and therefore serum creatinine, without affecting directly measured kidney function. In carriers, that means creatinine-based eGFR reads lower than the true GFR, providing a concrete biological explanation for part of the residual bias long observed in creatinine-based estimates among people of African ancestry, and reinforcing why race coefficients were the wrong fix.

The practical message is to treat a modestly reduced creatinine-based eGFR with appropriate caution where non-renal determinants of creatinine may be at play, and to confirm with a cystatin C-based estimate or measured GFR before labelling CKD or adjusting drug doses on creatinine alone.

Creatinine-based eGFR depends on creatinine production, not only renal clearance.
An African-ancestry-specific GATM variant raises creatine synthesis and serum creatinine.
It does not affect directly measured kidney function, so eGFR reads falsely low in carriers.
This explains part of the long-observed bias in creatinine-based eGFR.
Confirm with cystatin C or measured GFR before labelling CKD on creatinine alone.

Why it matters

It gives a biological reason creatinine eGFR can mislabel kidney function, and underlines why cystatin C, not a race coefficient, is the fix.

Don't overread it

This is an editorial on a biological mechanism, not a management trial; it explains part of the bias, and does not quantify how often it changes a clinical decision.