Serum creatinine comes from muscle, so a creatinine-based eGFR is a filtration estimate wearing a body-composition disguise. In most patients that does not matter. In the patients where it does, it matters a great deal, and the error runs in the direction most likely to cause harm.
The eGFR is overestimated, meaning true function is worse than the number suggests, in anyone with low muscle: the frail older patient, the person with cirrhosis, sarcopenia, malnutrition, spinal cord injury or an amputation, and many patients with advanced cancer. A creatinine of 70 micromol/L in a 45 kg woman of 82 is not reassuring. The eGFR is underestimated, meaning function is better than it looks, in the muscular young man, the bodybuilder, and after a large meat meal or creatine supplementation.
When the number and the patient disagree, the answer is cystatin C, which is produced by all nucleated cells and is not muscle-dependent. A combined creatinine-cystatin C equation is more accurate than either alone. Reach for it before making a decision that turns on the number: dosing a drug with a narrow margin, deciding on contrast, judging transplant candidacy, or telling someone they have chronic kidney disease. Also check the obvious confounders first, since trimethoprim and cimetidine raise creatinine by blocking its tubular secretion without any change in filtration at all.
- Suspect an overestimated eGFR in the frail, cirrhotic, sarcopenic, amputee or spinal-injured patient
- Suspect an underestimated eGFR in a heavily muscled young adult, or after a large meat meal or creatine supplements
- Order cystatin C, ideally with a combined equation, when the eGFR and the patient do not match
- Rule out trimethoprim and cimetidine before investigating an isolated creatinine rise
- Use a measured or cystatin-based estimate before decisions that turn on the exact number, such as narrow-margin drug dosing or transplant assessment
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