In a healthy 44‑year‑old man with a very muscular build, how much lower is the creatinine‑based estimated glomerular filtration rate (eGFR) expected to be, especially if he is taking a creatine supplement?

Impact of High Muscle Mass and Creatine Supplementation on eGFR

In a very muscular 44-year-old man taking creatine supplements, creatinine-based eGFR will be falsely reduced by approximately 6 mL/min per 10 kg of excess lean muscle mass, potentially underestimating true kidney function by 10–30% or more depending on the degree of muscularity. 1, 2

Mechanism of eGFR Underestimation in Muscular Individuals

• Creatinine generation increases proportionally with muscle mass because creatinine is a breakdown product of creatine phosphate in skeletal muscle, causing serum creatinine to rise independent of kidney function. 1

• Standard eGFR equations (CKD-EPI, MDRD) systematically underestimate true GFR in highly muscular individuals because these formulas assume average muscle mass for a given age, sex, and race—they cannot account for supraphysiologic muscularity. 1, 2

• The magnitude of error is quantifiable: research demonstrates that eGFR is falsely reduced by approximately −6 mL/min per 10 kg of excess lean muscle mass. 2

• Creatine supplementation compounds this effect by increasing both muscle creatine stores and creatinine production, further elevating serum creatinine without any decline in actual kidney function. 1

Quantifying the Expected Reduction

• In a very muscular individual with 10–20 kg more lean mass than average, expect eGFR to underestimate true GFR by roughly 6–12 mL/min from muscle mass alone. 2

• Creatine supplementation (typical dose 3–5 g/day) can raise serum creatinine by an additional 0.1–0.3 mg/dL, which translates to a further 5–15 mL/min reduction in calculated eGFR depending on baseline creatinine and age. 1

• Combined effect: a highly muscular 44-year-old man on creatine may have an eGFR that is 10–30 mL/min lower than his true GFR, potentially misclassifying normal kidney function (true GFR ~100–120 mL/min) as Stage 2 CKD (eGFR 60–89 mL/min). 1, 2

Diagnostic Performance in Muscular Patients

• Specificity of creatinine-based eGFR drops to 47% in the highest muscle-mass quartile, meaning more than half of muscular individuals with normal kidney function will be incorrectly flagged as having reduced GFR. 2

• Positive predictive value for detecting true CKD Stage 3 falls to 55% in highly muscular patients, making creatinine-based eGFR unreliable for both screening and clinical decision-making in this population. 2

When to Use Alternative Assessment Methods

• Measure cystatin C and calculate eGFRcr-cys (combined creatinine-cystatin C equation) when extreme muscle mass is present, as cystatin C is independent of muscle mass and provides more accurate GFR estimates. 1, 3

• Consider direct measured GFR using exogenous filtration markers (iothalamate, iohexol) if precise kidney function is required for critical decisions such as nephrotoxic drug dosing or pre-operative risk assessment. 1

• Do not use 24-hour urine creatinine clearance as an alternative, because it overestimates true GFR by 10–40% (creatinine is both filtered and secreted) and the error worsens with higher muscle mass. 4

Clinical Algorithm for Muscular Patients

1. Recognize the clinical context: very muscular build, bodybuilding, creatine supplementation, high-protein diet. 1

2. Calculate standard eGFRcr using the 2021 race-free CKD-EPI equation as the initial screen. 1

3. If eGFRcr is 45–89 mL/min/1.73 m² in a muscular patient, measure serum cystatin C and compute eGFRcr-cys to confirm whether kidney function is truly reduced or if the low eGFR is artifact from high muscle mass. 1, 3

4. If eGFRcr-cys remains discordant or clinical suspicion for normal kidney function is high, arrange measured GFR with exogenous markers to establish true baseline renal function. 1

Critical Pitfalls to Avoid

• Never rely on serum creatinine or eGFRcr alone in muscular individuals—doing so will systematically underestimate kidney function and may lead to unnecessary nephrology referrals, inappropriate medication dose reductions, or unwarranted exclusion from clinical trials. 1, 2

• Do not assume "normal" eGFR rules out the muscle-mass effect—even an eGFR of 90 mL/min may represent a true GFR of 110–120 mL/min in a highly muscular person. 2

• Recognize that creatine supplementation is a modifiable factor—if precise GFR assessment is needed, consider discontinuing creatine for 1–2 weeks and remeasuring creatinine, though this is rarely necessary if cystatin C or measured GFR is available. 1