Estimated GFR from creatinine assumes the patient generates creatinine at the rate the equation's development population did. That assumption fails predictably in three directions: the patient with very low muscle mass — elderly, malnourished, cirrhotic, amputee, or on long-term steroids — will have a creatinine that looks reassuring while their true filtration is substantially worse; the heavily muscled patient or the one taking creatine supplements will look worse than they are; and the patient whose muscle mass is actively changing will appear to have a kidney trajectory that is really a body-composition trajectory.
The failure mode that causes harm is the first one. A frail 78-year-old with a creatinine of 90 micromol/L can have a measured GFR well below what that number suggests, and the drugs dosed on the estimate — metformin, direct oral anticoagulants, gabapentin, many antibiotics — will be dosed for a kidney they do not have.
Cystatin C is the practical check, because it is produced by all nucleated cells and is largely independent of muscle. Where it is unavailable, a 24-hour creatinine clearance is still better than an estimate that the patient's body habitus has invalidated.
- Request cystatin C where body habitus makes the creatinine-based estimate unreliable, before dosing a renally cleared drug
- Suspect overestimated function in the frail, cachectic, cirrhotic or amputee patient with a normal-looking creatinine
- Ask about creatine supplements in anyone with an unexplained rise in creatinine and no other features of kidney disease
- Interpret an eGFR trend alongside weight change; a falling weight can manufacture an apparently improving eGFR
- Where neither cystatin C nor measured clearance is available, dose cautiously and recheck rather than trusting the number
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