Creatinine in Athletes: When Kidney Function Tests Mislead
Table of Contents
Introduction
Athletes represent a distinct population in whom creatinine measurements are frequently influenced by factors such as greater muscle mass, training load, and supplementation. As a result, values may differ from general population expectations without necessarily indicating kidney dysfunction.
Standard laboratory reference ranges for creatinine, as well as the equations used to estimate kidney function, were developed for the general population and may not accurately reflect individuals with substantially higher muscle mass. This can lead to misleading interpretations, unnecessary concern, and additional testing. Understanding why this happens, and what to do about it, is essential knowledge for anyone preparing for blood tests as an athlete or interpreting results for one.
In clinical practice, creatinine levels should always be interpreted in the context of the patient’s current condition, muscle mass, and level of athletic activity.
Why Creatinine in Athletes Is Higher: The Muscle Mass Mechanism
Creatinine is a metabolic waste product formed through the breakdown of creatine and phosphocreatine in skeletal muscle. Because total muscle mass is the primary determinant of the body’s creatine pool size, more muscle means more creatinine production—irrespective of how well the kidneys are functioning [1].
This relationship has been documented consistently in elite sports populations. In a study of 151 professional athletes across five sports—rugby, soccer, alpine skiing, sailing, and cycling—researchers found a significant positive correlation between serum creatinine and body mass index (r = 0.48, p<0.001) [1]. Rugby players, who carried the highest BMI (mean 28.83 ± 2.41 kg/m²), showed the highest creatinine concentrations at 1.31 ± 0.12 mg/dL, while cyclists showed values of only 0.91 ± 0.07 mg/dL [1].
The practical implication is clear: applying sedentary-population reference ranges (typically 0.7–1.3 mg/dL for men) to athletes may flag elevated values in muscular individuals for reasons unrelated to kidney disease, because those ranges were not calibrated for athletic body compositions. This is one of the most consistent patterns seen across which blood tests athletes actually need—standard ranges often don’t translate.
In clinical practice, I often see that athletic patients have greater muscle mass than sedentary individuals, which can influence serum creatinine levels. For this reason, I don’t interpret creatinine in isolation, but always in the context of the patient’s overall clinical picture. I also take into account that athletes may present with transient dehydration—especially if testing is done after recent training—which can further affect creatinine measurements.
The eGFR Problem: Why Estimated Kidney Function Is Unreliable in Athletes
Estimated glomerular filtration rate (eGFR) is intended to correct for the limitations of raw creatinine values, factoring in age, sex, and—depending on the equation—body weight. The most widely used formulas include the CKD-EPI and MDRD equations. In athletes, however, these calculations introduce systematic error.
Because eGFR equations are derived from and validated in general population samples, they may not account for the disproportionate muscle mass that drives creatinine production in athletes. A review specifically examining this issue concluded that serum creatinine in athletes is related to BMI, and therefore the use of general population reference ranges should not be recommended in sports medicine [2]. The same review noted that prediction of GFR in athletes using creatinine-based equations is questionable due to the anthropometric characteristics of athletic populations—particularly elevated BMI driven by muscle rather than fat [2].
Research in 490 Olympic athletes confirmed formula-dependent discrepancies in practice. When the same creatinine values were fed into different eGFR formulas, the Cockcroft-Gault equation produced significantly lower eGFR estimates for endurance athletes (113.6 ± 27 mL/min/1.73 m²) compared to skills athletes (122.6 ± 30.8, p = 0.008), while CKD-EPI showed no significant difference between groups—illustrating how formula choice can materially affect the interpretation of kidney function in athletic populations [3].
A study of 130 male athletes found that serum creatinine levels and eGFR calculated from creatinine (eGFRcre) correlated significantly with muscle mass, raising concern that creatinine-based assessments may be biased in athletes [4].
Patients often become concerned when their eGFR appears reduced, which is commonly driven by a relatively higher creatinine level. It is important to remember that commonly used eGFR equations are based on serum creatinine along with factors such as age and sex, and do not fully account for differences in muscle mass or body composition. As a result, in individuals with higher muscle mass—such as athletes—eGFR values may fall outside the reference range and appear lower than expected, even when true kidney function is normal. For this reason, clinical context remains essential when interpreting these results.
Cystatin C: A More Reliable Marker for Athletic Populations
Cystatin C is a small protein produced by every nucleated cell in the body. It is generally considered less dependent on muscle mass than creatinine, which makes it a more useful filtration marker in populations where muscle mass varies widely [5].
However, cystatin C is not entirely independent of body composition. The same study of 130 male athletes found that cystatin C and eGFR calculated from cystatin C (eGFRcys) were also significantly correlated with muscle mass [4]. Despite this, cystatin C can be useful as a complementary marker when creatinine results are ambiguous in muscular individuals.
In athletes who use creatine supplements (which further elevates serum creatinine, as discussed below), cystatin C-based assessment provides a more muscle-independent estimate of filtration capacity. Clinical guidance supports considering cystatin C when creatinine may be unreliable due to abnormal muscle mass, diet, or supplement use [5].
In many cases where elevated creatinine raises concern for possible kidney dysfunction, or where this needs to be ruled out, the situation is often further assessed using cystatin C and cystatin C–based eGFR. This can help clarify whether the finding reflects true impairment or is influenced by factors such as muscle mass. In practice, this approach often also helps reassure patients when results are consistent with normal kidney function.
This difference is expected, as cystatin C is generally less influenced by muscle mass than creatinine, making it useful for distinguishing between physiological and pathological causes of elevated creatinine. However, cystatin C is not as widely used in routine clinical practice as creatinine, and it is not always included in standard laboratory panels. In many settings, it requires a separate clinical decision and specific laboratory request.
Creatine Supplementation: Elevating Creatinine Without Impairing Kidneys
Creatine monohydrate supplementation is among the most widely used ergogenic aids in sport. It directly increases skeletal muscle creatine and phosphocreatine stores, which in turn increases the rate at which creatinine is produced as a breakdown product. The result is a predictable rise in serum creatinine that can be misread as evidence of declining kidney function.
A 2025 systematic review and meta-analysis of 21 studies found that creatine supplementation was associated with a small but statistically significant increase in serum creatinine (MD: 0.07 µmol/L; 95% CI: 0.01 to 0.12; p = 0.03) [6]. No significant changes were observed in GFR across these studies, indicating that the creatinine elevation reflects metabolic turnover rather than actual renal impairment [6].
Earlier research reached consistent conclusions. Short- and long-term creatine supplementation across a range of doses (5 g/day to 30 g/day) and durations (5 days to 5 years) had no known significant effects on studied indices of kidney function—including GFR—in healthy athletes and bodybuilders without pre-existing kidney disease [7]. In a randomized, double-blind, placebo-controlled trial in healthy sedentary males undergoing aerobic training, high-dose creatine supplementation (~10 g/day) over 3 months did not cause renal dysfunction; cystatin C levels decreased over time in both the creatine and placebo groups (PRE CR: 0.82 ± 0.09 vs. POST 12 CR: 0.71 ± 0.06 mg/L, P = 0.0001) [8].
In a healthy athlete using creatine, elevated serum creatinine may reflect metabolic turnover rather than kidney damage. Cystatin C measurement is the appropriate tool when clinical reassurance is needed.
This is particularly important to keep in mind in weightlifters and strength athletes, who more commonly use creatine supplementation. While creatine use is not limited to these groups, it is especially prevalent among individuals aiming to improve performance in resistance training. Even recreational athletes without a competitive background may use creatine for this purpose.
In these individuals, serum creatinine is often elevated, reflecting increased creatine turnover rather than impaired kidney function. In clinical practice, it can be reasonable to pause creatine supplementation for a short period—such as about a week—and then repeat testing, to help clarify whether the elevation is related to supplementation rather than underlying renal dysfunction.
Dehydration and Acute Kidney Injury: When Creatinine Elevation Is Real
Not all elevated creatinine in athletes reflects muscle mass or supplement use. Dehydration—particularly during prolonged or high-intensity exercise—can cause genuine, if typically transient, reduction in kidney function. This distinction matters clinically.
During sustained exercise, cardiac output is redirected toward working muscles, reducing renal blood flow. Simultaneously, dehydration concentrates waste products in the blood, including creatinine, producing a rise that may reflect reduced filtration rather than simply higher production. Research has shown that AKI incidence following prolonged endurance events—diagnosed by changes in serum creatinine—has been reported at anywhere from 4% to 85%, with hypohydration identified as a contributing factor [9]. The wide range reflects differences in race conditions, distance, temperature, and hydration strategy across studies. Notably, maintaining euhydration with water ingestion during physical work in the heat has been shown to attenuate rises in AKI biomarkers [9]. Research in healthy adult males further confirmed that prolonged exercise until ~3% hypohydration was associated with a significant decline in eGFR and increases in kidney injury biomarkers, while acute exercise with low-level dehydration had minimal effect [10].
The practical implication: creatinine drawn immediately post-race in a dehydrated athlete requires different interpretation than creatinine measured in the same athlete 24–48 hours post-race after full rehydration. This timing question is central to interpreting any post-marathon blood work—transient elevations that normalise with rehydration support a functional mechanism; persistent elevation warrants further investigation.
From a clinical perspective, particular caution is warranted in athletes at risk of significant muscle breakdown, such as rhabdomyolysis. This condition can markedly increase the risk of dehydration and acute kidney injury. It may occur, for example, in endurance athletes such as marathon runners, especially under conditions of prolonged exertion, heat, or inadequate fluid intake.
Patients should be advised to monitor warning signs. Severe muscle pain, weakness, and dark-colored urine may indicate more than simple dehydration and raise suspicion for rhabdomyolysis. In such cases, kidney function markers can rise substantially.
If rhabdomyolysis is suspected, urgent medical evaluation is required. Early management typically includes prompt intravenous fluid therapy to support renal perfusion and reduce the risk of acute kidney injury.
NSAIDs and Kidney Risk in Runners: A Cause for Concern
Perhaps the most clinically relevant kidney risk facing endurance athletes is the combination of dehydration and non-steroidal anti-inflammatory drug (NSAID) use. NSAIDs—including ibuprofen and naproxen—are consumed by a large proportion of endurance athletes, often during events where dehydration risk is highest.
A scoping review of 30 studies examining NSAID use in marathon and ultraendurance running found NSAID prevalence rates as high as 84% in triathletes and 88% of recreational runners consuming some form of the drug within a 12-month period [11]. While the same review noted that clear statistically significant links between NSAID use and adverse renal outcomes in ultraendurance running remain limited, it identified AKI as one of the key areas of concern warranting further study [11].
Data from a separate systematic review of severe AKI cases in endurance athletes found that 18 of 27 case report individuals (67%) with renal failure requiring hospital treatment following an endurance event had taken an NSAID [12].
The mechanism is well-established: NSAIDs inhibit cyclooxygenase, reducing renal prostaglandin synthesis and disrupting the compensatory vasodilation response that maintains glomerular blood flow when overall renal perfusion is reduced [13]. During exercise, when renal blood flow is already reduced, this protective mechanism becomes particularly important. NSAID-induced inhibition can precipitate hemodynamically-mediated AKI or, less commonly, acute interstitial nephritis [13].
In my clinical practice, I am generally cautious about recommending NSAID use in endurance athletes, particularly in situations involving prolonged exercise or potential dehydration. When analgesia is necessary, I tend to prefer paracetamol (acetaminophen), as it does not have the same effects on renal blood flow as NSAIDs.
Conclusion
In summary, interpreting kidney function in athletes requires a fundamentally different approach than in the general population. Elevated creatinine and reduced eGFR values are often driven by physiological factors such as increased muscle mass, training load, supplementation, or transient dehydration rather than true renal impairment. This makes isolated laboratory values potentially misleading if taken out of context.
A structured, clinically grounded interpretation—taking into account baseline values, timing of exercise, hydration status, and supplement use—is essential. When uncertainty remains, cystatin C can serve as a useful complementary marker, helping to distinguish between physiological variation and genuine pathology. At the same time, clinicians must remain vigilant for true red flags, such as persistent abnormalities, rhabdomyolysis, or the combined effects of dehydration and NSAID use.
Ultimately, the goal is not to dismiss abnormal results, but to interpret them appropriately. In athletic populations, this means balancing biochemical data with clinical context to avoid both overdiagnosis and missed pathology.
References
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC2579448/
[2] https://pubmed.ncbi.nlm.nih.gov/19317520/
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC12072620/
[5] https://www.ccjm.org/content/92/9/546
[6] https://pmc.ncbi.nlm.nih.gov/articles/PMC12590749/
[7] https://pubmed.ncbi.nlm.nih.gov/30367015/
[8] https://pubmed.ncbi.nlm.nih.gov/18188581/
[9] https://pubmed.ncbi.nlm.nih.gov/33774615/
[10] https://pmc.ncbi.nlm.nih.gov/articles/PMC5995308/
[11] https://pmc.ncbi.nlm.nih.gov/articles/PMC10840051/
