Creatine Supplementation and the Kidneys: The Creatinine Connection
Updated: Dec 2
In a prior blog titled “Rhabdomyolysis: Does Caffeine or Creatine Increase Your Risk?”, I was curious about a statement made from a physician about cases of rhabdomyolysis—the excessive breakdown of muscle cells–and how both caffeine and creatine could also cause the medical condition. Granted, the correlation with caffeine was with excessively high doses and creatine didn’t show a causative relationship. But this had me thinking about kidney health and creatine.
Does creatine supplementation negatively affect kidney function? No, and this topic has been reviewed elsewhere. See Antonio et al. (2021) and Rawson (2018). (1,2)
Yet in my experience working as a sports dietitian, there have been two incidences of athletes supplementing with creatine with slightly concerning lab values or blood pressure readings and, in both scenarios, the physician advised the athlete to immediately cease their creatine supplementation. In the former the athlete had known previous kidney damage (eGFR in the high 50s, no other flags) and the latter the athlete reported having white coat syndrome, or a higher blood pressure reading when at the doctor’s office compared to when at home.
The goals of this article include:
Kidney labs and the role of blood pressure.
How being an athlete can affect kidney labs.
A review on creatine supplementation and kidney health.
The importance of supplement safety.
A Quick Summary Up Front
Kidneys are meant to filter the blood to ensure accumulation of certain substances is kept in check. Creatinine is one of those substances: A high creatinine affects an equation estimating the filtration rate (the eGFR), thereby lowering its value, and is used alongside albumin to affect a ratio also used in evaluating kidney health (ACR). So if creatinine is high, it has a domino effect on other values.
The assumption is that a high creatinine level is because it's accumulating and not being filtered by the kidneys (a correct assumption when someone's kidneys are not filtering adequately, as is the case in chronic kidney disease).
However, athletes consuming higher protein levels, partaking in training loads enhancing muscle damage, and taking creatine supplements all independently increase the body's creatinine production. Again, affecting the GFR and ACR. However, there's no kidney damage. Creatinine on its own does not indicate kidney damage, but may prompt further inquiry by a physician.
Kidney Labs and Blood Pressure
The Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for kidney disease is updated regularly, including their most recent update in 2024. (3)
For those with chronic kidney disease (CKD), there are six stages of categorization, which is important as a stage defines the level of clinical intervention. The stages are categorized based on a patient’s glomerular filtration rate (GFR) and albuminuria (and ACR, the albumin-to-creatinine ratio).
GFR
The body excretes waste products through the lungs, sweat, feces, and urine, the latter being produced by the kidneys. Humans are born with two kidneys that constantly filter the blood and the GFR evaluates how well the kidneys are completing this function. (4)
For blood work, a true GFR is not often measured (mGFR), rather predicted by a formula to provide an estimated GFR, or eGFR. An eGFR equation often uses creatinine, which is the current recommendation from the 2021 National Kidney Foundation and the American Society of Nephrology Task Force. (4,5)
Albuminuria
This is the presence of the albumin protein in one’s urine. To collect this data point, urine needs to be tested—not blood. (6) Normally-functioning kidneys should not be releasing much protein, whereas a damaged kidney will.
The ACR is the albumin-to-creatinine ratio, which can be used alongside the AER (albumin excretion ratio). ACR evaluates albumin (in milligrams) over creatinine (in grams). (3,6) Concerning levels for kidney health would be an ACR >30 mg/g or >3 mg/mmol and/or an AER >30 mg/24 hours, either measurement consistently elevated over a three-month period. (3)
Cystatin C
This is another protein that can accumulate in the blood if the kidneys aren’t filtering adequately. Cystatin C as a blood value can also be used to calculate eGFR via the 2012 CKD-EPI cystatin C equation. (5,7) A 12-week study evaluating creatine supplementation (10 grams per day) resulted in an increased serum creatinine, but an unchanged cystatin C value. (8)
Blood Pressure
Evaluating blood pressure provides insight on the impact or stress on the artery walls, and they can only stretch so much (like a hair elastic). Blood is pumped through the heart, but its pressure is felt throughout every blood vessel in the body, including those of the kidneys, and can place additional stress on them. Blood pressure is like a water hose watering a garden of delicate flowers. Some water is good (normal blood pressure), but too much flattens the flowers (e.g., a high blood pressure or a water hose unnecessarily on full blast).
The higher the pressure is and the longer that pressure torments the blood vessels in the kidneys, the greater the likelihood of blood vessel damage. Damaged kidneys can no longer filter the blood as readily, allowing waste products that should have been removed in the urine to continue to circulate in the blood, potentially causing toxicity, and further increasing one’s blood pressure. (9)
A normalized value of under 120/80 mmHg is recommended. Both numbers evaluate the pressure the blood exerts within the artery walls when the heart beats (i.e., the top number called systolic blood pressure) and when the heart muscle rests in between beats (i.e., the bottom number called diastolic blood pressure). (10)
The Interaction of Muscles and Kidneys: Creatine vs. Creatinine
They are not the same thing, but are related.
Creatine is naturally produced in the liver (and to a smaller extent in the kidneys and pancreas), is stored in the skeletal muscles, and can be obtained from the diet, mainly from red meat and fish. (11,12) When producing energy within the muscles through the phosphagen system, phosphocreatine and ADP interact with the enzyme creatine kinase to produce creatine and ATP (energy).
Both creatine and phosphocreatine are converted into creatinine in a spontaneous and irreversible manner, at a rate of 2% per day. (12,13)
Creatinine is a waste product of dietary protein intake and skeletal muscle metabolism that is then filtered out of the body by the kidneys. Often, an athlete’s creatinine levels will be higher than the average adult, which makes sense because their turnover of muscle breakdown is expected to be higher due to their enhanced training load. A higher dietary protein intake (and therefore dietary creatine intake for omnivores) is also expected to increase serum creatinine levels, doubling in the 2-4 hours after intake. Black men have been shown to have high serum creatinine levels, again related to their muscle mass. (12)
Given “plasma creatinine concentration is equal to its rate of production divided by its rate of excretion … clinicians can often assume by default that an elevated serum creatinine indicates that the kidneys are not clearing creatinine effectively [and] it is rarely considered that the body may in fact be producing creatinine in excess.” (12)
Creatine Supplementation Does Not Negatively Affect Kidney Health
Antonio et al. (2021) acknowledged how after more than 20 years of research, when taken in recommended doses there are no concerns connecting creatine supplementation with impaired kidney health. Concerns likely stemmed from a poor understanding of creatine metabolism and case studies incorrectly linking health impacts and death to creatine supplementation. (1,2)
Consider, too, that survey data has estimated that 8-74% of athletes and other exercisers report supplementing with creatine. (14) If creatine were so damaging to the kidneys, the rate of kidney damage should be quite high in athletes.
The Importance of Supplement Safety
I harp on this frequently when writing about supplements, but the supplement industry is poorly regulated and athletes should stick with products that are third-party certified by certifiers testing every lot of a supplement that is produced (e.g., NSF Certified for Sport, Informed Sport). Besides safety, the dose is also regulated.
Keep this in mind whenever reading about supplements being connected with X condition or concern. If the supplement is not third-party certified, how can you know for sure what’s in the supplement bottle? Could other banned substances be responsible for the concern? If for a case study there is no testing of the supplement to confirm the dose and ingredients, be cautious when interpreting results.
Take-Home Messages
With any data being tracked on an athlete, it’s always good to have a baseline to compare against. In the scenario of labs, account for supplement use as one would medications. For the former, understanding the dose, frequency, and brand used would be helpful to align at the time of bloods being drawn. With follow-up labs, you have more information and context to interpret any changes in the results.
If an athlete supplementing with creatine has higher serum creatinine levels (and lower eGFR levels when the predictive equation uses creatinine), research has shown that stopping creatine supplementation should reduce serum creatinine levels. (12) So long as no other indicator of kidney damage exists (e.g., dehydration, high blood pressure, kidney transplant) and there’s a good understanding that increased creatinine production differs from accumulation. Providers need to understand what goes into evaluating serum creatinine levels and utilize additional measures of kidney health.
For those with pre-existing kidney damage, take guidance from the physician in what they’re comfortable with. Possibly starting with a lower dose of 3-5 grams daily of creatine and monitoring blood pressure, a non-creatinine eGFR equation, albuminuria (and not only ACR), plus other metrics of kidney health would be productive, acknowledging serum creatinine will rise.
Ultimately, CKD can be fatal and is the ninth leading cause of death in the United States. (15) If physicians are ever concerned about someone’s kidney labs, the role of a dietitian is to provide education and context surrounding the athlete’s supplementation and overall nutrition.
References
(1) Antonio, J., Candow, D.G., Forbes, S.C., Gualano, B., Jagim, A.R., … & Ziegenfuss, T.N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? J Int Sports Nutr,18(1):13. https://pubmed.ncbi.nlm.nih.gov/33557850/
(2) Rawson, E.S. (2018). The safety and efficacy of creatine monohydrate supplementation: what we have learned from the past 25 years of research. Sports Science Exchange,31(186):1-6. https://www.gssiweb.org/sports-science-exchange/article/the-safety-and-efficacy-of-creatine-monohydrate-supplementation-what-we-have-learned-from-the-past-25-years-of-research
(3) Kidney Disease: Improving Global Outcomes (KDOQI) CKD Work Group. (2024). KDOQI 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int,105(4S):S117-S314. https://pubmed.ncbi.nlm.nih.gov/38490803/
(4) NKF Patient Education Team. (2022, July 13). Estimated glomerular filtration rate (eGFR). National Kidney Foundation. https://www.kidney.org/kidney-topics/estimated-glomerular-filtration-rate-egfr
(5) National Kidney Foundation (n.d.). eGFR calculator. https://www.kidney.org/professionals/gfr_calculator
(6) National Kidney Foundation (n.d.). ACR. https://www.kidney.org/kidney-health/kidneydisease/siemens_hcp_acr
(7) NKF Patient Education Team. (2023, July 26). Cystatin C. National Kidney Foundation. https://www.kidney.org/kidney-topics/cystatin-c
(8) Gualano, B., Ugrinowitsch, C., Novaes, R.B., Artioli, G.G., Shimizu, M.H., … & Lancha, Jr., A.H. (2008). Effects of creatine supplementation on renal function: a randomized, double-blind, placebo controlled clinical trial. Eur J Appl Physiol,103(1):33-40. https://pubmed.ncbi.nlm.nih.gov/18188581/
(9) National Institute of Diabetes and Digestive and Kidney Diseases. (2020, March). High blood pressure & kidney disease. https://www.niddk.nih.gov/health-information/kidney-disease/high-blood-pressure
(10) American Heart Association. (2024, May 17). Understanding blood pressure readings. https://www.heart.org/en/health-topics/high-blood-pressure/understanding-blood-pressure-readings
(11) Jeukendrup, A., & Gleeson, M. (2024). Sport Nutrition, fourth edition. Human Kinetics.
(12) Williamson, L., & New, D. (2014). How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology. BMJ Case Rep,2014(2014):1-4. https://pmc.ncbi.nlm.nih.gov/articles/PMC4170516/
(13) Longobardi, I., Gualano, B., Seguro, A.C., & Roschel, H. (2023). Is it time for a requiem for creatine supplementation-induced kidney failure? A narrative review. Nutrients,15(6):1466. https://pmc.ncbi.nlm.nih.gov/articles/PMC10054094/
(14) Rawson, E.S., Clarkson, P.M., & Tarnopolsky, M.A. (2017). Perspectives on exertional rhabdomyolysis. Sports Med,47(Suppl 1):33-49. https://pubmed.ncbi.nlm.nih.gov/28332112/
(15) CDC National Center for Health Statistics. (2024, April 28). Kidney disease. https://www.cdc.gov/nchs/fastats/kidney-disease.htm
