Creatine and the Kidneys: Why Creatinine May Be Elevated, But It Doesn't Necessarily Mean Kidney Damage

Creatine and creatinine are related substances, but they are not the same thing. Creatine is involved in the rapid energy recovery system in cells, while creatinine is formed during its spontaneous breakdown and is excreted by the kidneys. This is why the level of creatinine in the blood is often used as an indirect marker of kidney function.

The problem arises when creatinine is interpreted as a direct indicator of kidney damage. While creatine supplementation may increase its concentration slightly, it does not prove that glomerular filtration rate has deteriorated or that the kidneys have been damaged. To understand this difference, it is necessary to separate three things: the formation of creatinine, its concentration in the blood, and the actual filtration function of the kidneys.

How creatine is related to creatinine

Some of the creatine and phosphocreatine are converted non-enzymatically to creatinine every day. Creatinine then enters the blood and is mainly excreted by the kidneys. Therefore, its level depends not only on how well the kidneys filter the blood, but also on how much creatinine is produced.

This is especially important when taking creatine. As the total creatine pool in the body increases, the amount of substrate from which creatinine is formed may also increase. That is, an increase in serum creatinine can theoretically occur without structural damage to the kidneys.

We separately analyzed the basic biochemistry of creatine, phosphocreatine, and their role in cellular energetics in the material on what creatine monohydrate is and how it works.

Why high creatinine doesn't equal kidney damage

Creatinine is a convenient, inexpensive, and widely available laboratory marker, but it is not a direct measure of kidney tissue damage. Its concentration can be affected by muscle mass, nutrition, hydration, exercise, some medications, and the individual rate of creatinine formation.

Most standard eGFR formulas also use serum creatinine. This means that if creatinine is elevated for a reason unrelated to decreased filtration, the calculated eGFR may automatically appear lower. The formula does not “see” the cause of the elevation—it merely converts creatinine concentration and other variables into a mathematical estimate.

That is why methods that do not depend on creatinine are especially valuable in creatine studies: direct measurement of GFR by exogenous markers, cystatin C, as well as indicators of albuminuria, proteinuria, and markers of renal tubular damage.

What do the 2025–2026 meta-analyses show?

A systematic review and meta-analysis by Naeini et al. (2025) included 21 studies of creatine supplementation. The authors found a small statistically significant increase in serum creatinine but no statistically significant deterioration in GFR. Their conclusion was cautious: the change in creatinine may reflect metabolic turnover of creatine rather than a decline in renal function.

In 2026, Tsiaras et al. analyzed 19 randomized controlled trials and one randomized crossover trial. Serum creatinine was on average 0.13 mg/dL higher in the creatine groups, but there was no statistically significant difference in urea concentration or eGFR between the groups. The authors specifically emphasized that RCTs of more than one year are needed to confidently assess long-term renal safety.

Another meta-analysis in 2026, by de Souza Almeida et al., included 26 studies and 1036 participants. Serum creatinine was approximately 0.14 mg/dL higher, and GFR estimated by creatinine-dependent methods appeared to be lower. However, no statistically significant difference was found in GFR estimated by Cr-EDTA. There were also no significant differences in serum urea, albuminuria, or proteinuria.

This discrepancy is fundamental. If a creatinine-based indicator changes and a more direct method of assessing filtration does not confirm this, this supports the hypothesis that the marker itself is changing, and not necessarily that kidney function is deteriorating.

What do markers that do not rely solely on creatinine show?

One way to check whether creatinine is misleading is to look at other markers. In a randomized, double-blind study by Vilar Neto et al. (2020), 36 healthy, physically active men were given either placebo, 3 g of creatine per day, or 5 g per day for 35 days. The researchers assessed not only creatinine and eGFR, but also KIM-1 and MCP-1, biomarkers associated with kidney damage, as well as albuminuria and proteinuria.

There were no statistically significant differences in these parameters between the groups after 35 days. At the same time, in the intragroup comparison in the creatine groups, serum creatinine increased, and the calculated eGFR decreased, remaining within the reference range. This picture clearly demonstrates why a change in creatinine-based eGFR should not be automatically interpreted as damage.

Another approach is cystatin C. In a study by Gualano et al. (2008), 18 healthy men were given approximately 10 g of creatine per day or placebo for three months while doing aerobic exercise. Cystatin C showed no evidence of deterioration in renal function in the creatine group.

Cystatin C is also not a perfect marker and has its own influencing factors, but it is not formed from creatine. Therefore, in situations where a creatinine-based assessment is questionable, a creatine-independent marker can provide additional context.

Of particular importance are studies where GFR was not calculated from creatinine but measured by the clearance of an exogenous marker. In Lugaresi et al. (2013), participants who were strength training and consuming a high-protein diet received 20 g of creatine per day for the first 5 days and then 5 g per day for the remainder of the 12-week period.

GFR was measured by 51Cr-EDTA clearance. There was no statistically significant difference between creatine and placebo. Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria also remained unchanged.

Such data are important not because a single experiment can prove universal safety, but because it separates creatinine itself from the actual filtration capacity of the kidneys. This is the central problem in interpreting creatine background tests.

What to know for people with kidney disease

Most controlled studies have been conducted in healthy individuals or in selected clinical groups without severe renal impairment. Therefore, the conclusion that “a small increase in creatinine does not necessarily mean damage” cannot be translated into the statement that “creatine is safe for all kidney disease.”

The meta-analysis by de Souza Almeida et al. (2026) included both healthy participants and selected groups with chronic kidney disease, but the amount of data for CKD is significantly smaller than for people without established kidney disease. In addition, disease stage, comorbidities, medications, and methods of assessing kidney function may vary significantly.

In the presence of established kidney disease, persistently altered laboratory values, or drug therapy, interpretation of creatinine, eGFR, and other markers should be performed by a physician taking into account the full clinical context.

How to interpret tests if a person takes creatine

The first principle is not to hide your creatine intake from your doctor or the lab technician who interprets the results. This does not mean that any increase in creatinine should be automatically attributed to the supplement. On the contrary, information about creatine helps to avoid two opposite mistakes: unreasonably considering a change as a sign of damage or, conversely, ignoring a real problem.

The second principle is to look at the picture, not just one number. The dynamics of indicators, accompanying symptoms, blood pressure, urinalysis, albuminuria or proteinuria, previous results, muscle mass, level of physical activity, and other factors may be more important than a single creatinine value.

The third principle is to understand the limitations of eGFR. If the formula uses creatinine, it inherits all of its weaknesses. If necessary, the doctor can use additional assessment methods, such as cystatin C or more direct methods of measuring filtration. Which test is needed for a particular person depends on the clinical situation.

Where does the available data end?

Current meta-analyses generally do not show that small increases in serum creatinine during creatine supplementation are accompanied by concomitant deterioration in other measures of renal function. But this does not amount to proof of absolute safety for any individual, at any dose, or for any duration.

A significant proportion of RCTs are relatively short in duration, with fewer long-term studies lasting more than one year. Individual clinical groups are represented by small sample sizes. In addition, different studies use different doses, protocols, populations, and methods of assessing renal function.

Therefore, the most accurate conclusion is that in studies, mainly involving people without established renal pathology, creatine can slightly increase serum creatinine without a corresponding deterioration in direct or creatinine-independent indicators of renal function. Elevated creatinine alone does not allow us to establish the cause of the change.

Frequently asked questions

Can creatine increase blood creatinine?
Yes. Meta-analyses from 2025–2026 found a small mean increase in serum creatinine with creatine supplementation. This may be due to increased creatine turnover, not necessarily to decreased kidney function.

Does elevated creatinine mean that the kidneys are damaged?
No, not automatically. Creatinine is an indirect marker and does not depend solely on glomerular filtration. The cause of the change is assessed in the context of other tests and clinical data.

Why might eGFR decrease after starting creatine?
Many eGFR formulas use serum creatinine. If creatinine is elevated for reasons unrelated to decreased filtration, the mathematically calculated eGFR may also be lower.

What is cystatin C and why is it tested when taking creatine?
Cystatin C is another marker used to assess kidney function that is not derived from creatine and may be useful as an additional source of information when creatinine-based assessment is equivocal.

Have you examined albuminuria and proteinuria against the background of creatine?
Yes. Controlled trials and a 2026 meta-analysis found no statistically significant increases in albuminuria or proteinuria overall, although the results should not be extrapolated to all clinical situations.

Are the findings the same for healthy people and people with kidney disease?
No. Most of the data is in people without established kidney disease. For CKD, the evidence base is smaller and more heterogeneous, so individual medical evaluation is required.

One indicator does not give a complete picture. If necessary, the doctor takes into account the dynamics, urinalysis, albuminuria or proteinuria, cystatin C, concomitant conditions and other methods of assessing kidney function.

Sources

• Naeini EK and others. (2025). Effect of creatine supplementation on kidney function: a systematic review and meta-analysis. BMC Nephrology. PubMed
• Tsiaras V. and others. (2026). The effect of creatine supplementation on kidney function: a systematic review and meta-analysis of randomized controlled trials. Journal of Renal Nutrition. PubMed
• de Souza Almeida and others (2026). Impact of creatine supplementation on kidney health: a systematic review and meta-analysis. International Urology and Nephrology. PubMed
• Vilar Neto JO and others. (2020). Novel renal biomarkers show that creatine supplementation is safe: a double-blind, placebo-controlled randomized clinical trial. Toxicology Research. PubMed
• Lugaresi R. and others. (2013). Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? Journal of the International Society of Sports Nutrition. PubMed
• Gualano B. and others. (2008). Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial. European Journal of Applied Physiology. PubMed

Dietary supplement. Not a medicine. Consult a doctor before use.