- Design
- Commentary
- Population
- People of African ancestry with a GATM variant
- Primary outcome
- Effect of the variant on serum creatinine and eGFR bias
- Effect
- Raised serum creatinine without change in measured kidney function
This Kidney International commentary discusses the identification of an African ancestry-specific variant in the glycine amidinotransferase (GATM) gene. The variant increases creatine synthesis and therefore serum creatinine, without changing measured glomerular filtration rate.
This offers a biological explanation for part of the residual bias in creatinine-based eGFR in people of African ancestry, a bias that race-based correction factors tried, imperfectly, to address before most were dropped.
The broader lesson applies everywhere: creatinine reflects muscle and creatine metabolism as well as filtration. When a creatinine-based eGFR does not fit the clinical picture, measuring cystatin C or a combined equation can help.
- Creatinine-based eGFR can underestimate true GFR when creatinine production is high for non-renal reasons.
- Use cystatin C or combined creatinine-cystatin equations when eGFR does not fit the patient.
- Genetic variants, muscle mass and diet all influence creatinine independently of the kidney.
- Consider measured GFR when precise function matters, such as for drug dosing or kidney donation.
Why it matters
A mislabelled CKD stage affects drug dosing, eligibility for treatments and patient anxiety.
Don't overread it
This is a commentary on genetic findings; it does not propose a new equation or ancestry-based correction.
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