Three things on a laboratory report share most of a name. One is a waste product, one is an enzyme, one is the supplement — and only the first is on an ordinary panel. Reading any of them as the others is the single most common source of alarm about creatine, and it is a naming problem before it is a physiology problem. This is research journalism and contains no usage guidance, per our editorial standards.
The three entities, separated
| On the report | What it is | What it is used for |
|---|---|---|
| Creatinine | The waste product creatine degrades into | Estimating kidney filtration (eGFR) |
| Creatine kinase (CK) | An enzyme that moves a phosphate between phosphocreatine and ADP | A marker of muscle cell turnover or damage |
| Creatine | The compound itself, stored in muscle | Rarely measured; specialist assays for inherited creatine metabolism disorders |
They are not variants of one measurement. Creatinine is a molecule the kidneys clear; creatine kinase is a protein that leaks out of muscle cells; creatine is the substrate. A person who supplements creatine and then reads a routine panel is looking almost exclusively at the first row.
Creatinine: the marker that moves for a reason unrelated to the kidney
About 1 to 2% of the intramuscular creatine pool is converted to creatinine every day and excreted in urine. That steady relationship is precisely what makes serum creatinine useful as a filtration estimate — and precisely why raising the size of the muscle store changes the number. More stored creatine means more daily creatinine, independent of how well the kidney is filtering it.
The pooled evidence says the movement is small. A 2025 systematic review and meta-analysis of 21 studies, with 12 eligible for quantitative pooling (177 participants supplemented, 263 control), found:
- a small statistically significant increase in serum creatinine, mean difference 0.07 µmol/L (95% CI 0.01 to 0.12, p = 0.03);
- no statistically significant difference in glomerular filtration rate.
Its subgroup analysis by duration is oddly shaped and worth recording as published: significant at a follow-up of one week or less (MD 0.12, 95% CI 0.03 to 0.21), not significant between one and twelve weeks (MD 0.04, 95% CI −0.09 to 0.17), then significant again beyond twelve weeks. The authors' conclusion is that the rise is "likely due to metabolic turnover rather than renal impairment" (Naeini et al., BMC Nephrol 2025;26(1):622, PMID 41199218; doi:10.1186/s12882-025-04558-6).
One note on the printed unit, because it changes how the figure reads. Serum creatinine in adults is typically reported in the region of 60 to 110 µmol/L. A mean difference of 0.07 µmol/L, as printed, is a change of roughly a tenth of one per cent of a typical value. We report the figure exactly as the paper gives it and flag the scale rather than assume a conversion.
A discrepancy in an earlier meta-analysis, stated plainly
The 2019 meta-analysis in the Journal of Renal Nutrition is widely cited for the conclusion that creatine does not harm the kidney. Its abstract reads: creatine supplementation "did not significantly alter serum creatinine levels (standardized mean difference = 0.48, 95% confidence interval 0.24-0.73, P = .001...)" (de Souza e Silva et al., J Ren Nutr 2019;29(6):480–9, PMID 31375416).
A confidence interval that excludes zero with p = 0.001 is a statistically significant difference. The wording and the statistics in that sentence do not agree, and the same pattern repeats in the adjacent sentence about plasma urea. We are not asserting which side is the error; we are recording that the sentence is self-contradictory as printed, that it is checkable by anyone who opens the abstract, and that the 2025 meta-analysis above is both more recent and internally consistent. The broader kidney literature, including the trials that measured filtration directly rather than estimating it, is on creatine and the kidneys.
Creatine kinase: a different molecule, and a reference range built on the wrong people
Creatine kinase turns up on muscle and cardiac panels and is the one most often mistaken for a creatine measurement. It is an enzyme. Its appearance in serum reflects muscle cell membrane turnover — which training produces in abundance.
A 2018 study measured it in 27 professional male footballers in the Football League Championship and compared them with a published control group of military personnel:
| Group | Median CK |
|---|---|
| Professional footballers | 284 U/L |
| Military control group | 124 U/L |
The difference was significant at p < 0.001, and the authors proposed a 95% reference interval for professional footballers of 64.9 to 1971.7 U/L (Mahmutyazicioglu et al., BMJ Open Sport Exerc Med 2018;4(1):e000282, PMID 29387443).
Against a general-population upper limit in the low hundreds, an upper bound near 1,972 U/L is a different world. A trained person tested after hard sessions can sit far above a printed reference range and be entirely typical for their population. That is a property of who the range was built on, not of the person being tested — and it is a separate question from creatine supplementation entirely, since creatine kinase responds to training load rather than to intake.
Cystatin C: the second opinion, and why it often disagrees
Because creatinine production scales with muscle mass, a second filtration marker that does not come from muscle — cystatin C — is sometimes used alongside it. The two estimates frequently diverge, and the divergence is itself associated with poor outcomes, which has made it an active research question rather than a settled tiebreak.
A 2026 review in Current Opinion in Nephrology and Hypertension reports that models incorporating measured filtration by iothalamate, objective measures of muscle mass, obesity, inflammation and shrunken pore syndrome "have explained only a minority of the variation" in the difference between the two estimates, and that adjusting for those factors does not remove the association with outcomes. Its recommendation is that until it becomes possible to predict which estimate is more accurate for a given patient, the combined equation should be favoured (McCoy IE, PMID 41816809).
The useful implication for this page is narrow and honest: "get a cystatin C instead" is often offered as a clean answer to the creatinine confusion, and the nephrology literature does not treat it as one.
The honest summary
- A routine panel shows creatinine, not creatine. Creatine itself is seldom measured outside specialist testing.
- Creatine kinase is an unrelated enzyme reporting muscle turnover; its reference ranges were not built on trained populations, and a proposed footballer interval runs to 1,971.7 U/L.
- Supplementation is associated with a small rise in serum creatinine and no significant change in the filtration estimate across pooled trials, attributed by the authors to turnover rather than damage.
- A widely cited 2019 meta-analysis states a non-significant conclusion alongside statistics that are significant; the discrepancy is in the published abstract.
- Cystatin C is not a clean tiebreak — the causes of its disagreement with creatinine remain poorly understood.
Related pages on this site: what creatine is for the store and turnover figures behind the creatinine relationship, creatine and the kidneys for the trials that measured filtration directly, and creatine side effects for the two evidence streams on safety.
This page describes what laboratory markers represent. It is not diagnostic guidance, it interprets no individual's results, and any blood test result belongs with the clinician who ordered it.
Sources
- Naeini EK, Eskandari M, Mortazavi M, Gholaminejad A, Karevan N. Effect of creatine supplementation on kidney function: a systematic review and meta-analysis. BMC Nephrol 2025;26(1):622 — PMID 41199218 · doi:10.1186/s12882-025-04558-6
- de Souza e Silva A, Pertille A, Reis Barbosa CG, et al. Effects of creatine supplementation on renal function: a systematic review and meta-analysis. J Ren Nutr 2019;29(6):480–9 — PMID 31375416
- Mahmutyazicioglu J, Nash J, Cleves A, Nokes L. Is it necessary to adjust current creatine kinase reference ranges to reflect levels found in professional footballers? BMJ Open Sport Exerc Med 2018;4(1):e000282 — PMID 29387443
- McCoy IE. Implications of the cystatin C/creatinine discordance. Curr Opin Nephrol Hypertens 2026;35(3):323–8 — PMID 41816809
- Kreider RB, Kalman DS, Antonio J, et al. ISSN position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 2017;14:18 — PMID 28615996 — source for the 1–2% daily degradation figure
All sources retrieved 2026-09-16. Digital object identifiers verified by content negotiation on the same date.