The impact of creatine supplementation on the development of kidney disease – literature review
DOI:
https://doi.org/10.12775/QS.2025.38.57864Keywords
creatine, supplementation, kidney, kidney disease, sportAbstract
Introduction: Creatine, a widely studied dietary supplement, is known for enhancing athletic performance and muscle strength. Concerns persist regarding its impact on kidney health, as it raises serum creatinine levels, potentially confounding renal function assessments. This review examines creatine’s role in sports and clinical contexts, emphasizing safety and kidney health implications.
Aim of the study: To assess the effects of creatine supplementation on kidney function by summarizing evidence from case studies, clinical trials, and long-term research, addressing safety concerns in healthy and at-risk individuals.
State of knowledge: Research supports creatine’s efficacy in improving athletic performance, recovery, and muscle strength, with therapeutic benefits in neurodegenerative diseases, type 2 diabetes, aging, and chronic conditions. Robust trials show no adverse renal effects in healthy individuals, even with long-term or high-dose use. However, case reports highlight potential risks for individuals with pre-existing kidney conditions, especially without monitoring. Elevated serum creatinine levels caused by creatine can mislead eGFR-based renal function tests, warranting cautious interpretation.
Conclusions: When used as recommended, creatine is safe and effective for improving athletic and clinical outcomes in healthy individuals. While no direct renal impairment has been observed, caution is essential for those with kidney conditions. Pre-supplementation renal assessments, individualized dosing, and regular monitoring are advised to minimize risks. Creatine remains a valuable supplement, and further research is needed to confirm its long-term safety across various populations.
References
1. Longobardi I, Gualano B, Seguro AC, Roschel H. Is It Time for a Requiem for Creatine Supplementation-Induced Kidney Failure? A Narrative Review. Nutrients. 2023; 15(6):1466. https://doi.org/10.3390/nu15061466
2. Kreider, R.B., Kalman, D.S., Antonio, J. et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14, 18 (2017). https://doi.org/10.1186/s12970-017-0173-z
3. Pritchard, N.R.; Kalra, P.A. Renal dysfunction accompanying oral creatine supplements. Lancet 1998, 351, 1252–1253.
4. Barisic, N.; Bernert, G.; Ipsiroglu, O.; Stromberger, C.; Muller, T.; Gruber, S.; Prayer, D.; Moser, E.; Bittner, R.E.; Stockler-Ipsiroglu, S. Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy. Neuropediatrics 2002, 33, 157–161.
5. Koshy, K.M.; Griswold, E.; Schneeberger, E.E. Interstitial nephritis in a patient taking creatine. N. Engl. J. Med. 1999, 340, 814–815.
6. Robinson, S.J. Acute quadriceps compartment syndrome and rhabdomyolysis in a weight lifter using high-dose creatine supplementation. J. Am. Board Fam. Pract. 2000, 13, 134–137.
7. Revai, T.; Sapi, Z.; Benedek, S.; Kovacs, A.; Kaszas, I.; Viranyi, M.; Winkler, G. Severe nephrotic syndrome in a young man taking anabolic steroid and creatine long term. Orv. Hetil. 2003, 144, 2425–2427.
8. Taner, B.; Aysim, O.; Abdulkadir, U. The effects of the recommended dose of creatine monohydrate on kidney function. NDT Plus 2011, 4, 23–24.
9. Thorsteinsdottir, B.; Grande, J.P.; Garovic, V.D. Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate. J. Ren. Nutr. 2006, 16, 341–345.
10. Gimenez I, Hugo C, Todorov VT. Editorial: Recent advances on renoprotection and kidney regeneration. Front Physiol. 2023;14:1204789. doi: https://10.3389/fphys.2023.1204789.
11. Silverthorn DU. Human Physiology: An Integrated Approach. 8th ed. Pearson Education; 2019.
12. Ross CR, Holohan PD. Transport of Organic Anions and Cations in Isolated Renal Plasma Membranes. Annual Review of Pharmacology and Toxicology. 1983;23(1):65-85. doi: https://doi.org/10.1146/annurev.pa.23.040183.000433
13. WEINER IM, MUDGE GH. RENAL TUBULAR MECHANISMS FOR EXCRETION OF ORGANIC ACIDS AND BASES. Am J Med. 1964;36:743-762. doi: https://doi.org/10.1016/0002-9343(64)90183-4
14. Hayslett JP. Functional adaptation to reduction in renal mass. Physiol Rev. 1979;59(1):137-164. doi: https://doi.org/10.1152/physrev.1979.59.1.137
15. Zsom L, Zsom M, Salim SA, Fülöp T. Estimated Glomerular Filtration Rate in Chronic Kidney Disease: A Critical Review of Estimate-Based Predictions of Individual Outcomes in Kidney Disease. Toxins. 2022;14(2):127. doi: https://doi.org/10.3390/toxins14020127.
16. Levey AS, Coresh J, Tighiouart H, Greene T, Inker LA. Measured and estimated glomerular filtration rate: current status and future directions. Nat Rev Nephrol. 2020;16(1):51-64. doi: https://doi.org/10.1038/s41581-019-0191-y
17. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med. 2006;354(23):2473-2483. doi: https://doi.org/10.1056/NEJMra054415
18. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C [published correction appears in N Engl J Med. 2012 Aug 16;367(7):681] [published correction appears in N Engl J Med. 2012 Nov 22;367(21):2060]. N Engl J Med. 2012;367(1):20-29. doi: https://doi.org/10.1056/NEJMoa1114248
19. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev. 2000;80(3):1107-1213. doi: https://doi.org/10.1152/physrev.2000.80.3.1107
20. Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol. 1997;76(6):566-567. doi: https://doi.org/10.1007/s004210050291
21. Gualano B, Ferreira DC, Sapienza MT, Seguro AC, Lancha AH Jr. Effect of short-term high-dose creatine supplementation on measured GFR in a young man with a single kidney. Am J Kidney Dis. 2010;55(3):e7-e9. doi: https://doi.org/10.1053/j.ajkd.2009.10.053
22. Alves CR, Santiago BM, Lima FR, et al. Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2013;65(9):1449-1459. doi: https://doi.org/10.1002/acr.22020
23. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci (Lond). 1996;91:113-118. doi: https://doi.org/10.1042/cs0910113
24. Poortmans J, Francaux M. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;352:234. doi: https://doi.org/10.1016/S0140-6736(05)79293-1
25. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31:1108-1110. doi: https://doi.org/10.1097/00005768-199907000-00021
26. Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M. Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc. 2005;37:1717–1720. doi: https://doi.org/10.1249/01.mss.0000181670.35152.db
27. Mihic S, MacDonald JR, McKenzie S, Tarnopolsky M. Acute creatine loading increases fat-free mass but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc. 2000;32:291-296. doi: https://doi.org/10.1097/00005768-200002000-00011
28. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some hematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med. 2000;34:284-288. doi: https://doi.org/10.1136/bjsm.34.4.284
29. Mayhew DL, Mayhew JL, Ware JS. Effects of long-term creatine supplementation on liver and kidney functions in American college football players. Int J Sport Nutr Exerc Metab. 2002;12:453-460. doi: https://doi.org/10.1123/ijsnem.12.4.453
30. Brose A, Parise G, Tarnopolsky MA. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci. 2003;58:11-19. doi: https://doi.org/10.1093/gerona/58.1.B11
31. Eijnde BO, Van Leemputte M, Goris M, et al. Effects of creatine supplementation and exercise training on fitness in men 55–75 yr old. J Appl Physiol. 2003;95:818-828. doi: https://doi.org/10.1152/japplphysiol.01048.2002
32. Kreider RB, Melton C, Rasmussen CJ, et al. Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem. 2003;244:95–104. doi: https://doi.org/10.1023/A:1022466531579
33. Groeneveld GJ, Beijer C, Veldink JH, et al. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int J Sports Med. 2005;26:307–313. doi: https://doi.org/10.1055/s-2004-821209
34. Cancela P, Ohanian C, Cuitiño E, Hackney AC. Creatine supplementation does not affect clinical health markers in football players. Br J Sports Med. 2008;42:731–735. doi: https://doi.org/10.1136/bjsm.2007.038489
35. Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28:172–178. doi: https://doi.org/10.1016/j.nutres.2008.02.004
36. Gualano B, Ugrinowitsch C, Novaes RB, et al. Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial. Eur J Appl Physiol. 2008;103:33–40. doi: https://doi.org/10.1007/s00421-007-0659-0
37. Spillane M, Schoch R, Cooke M, et al. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. J Int Soc Sports Nutr. 2009;6:6. doi: https://doi.org/10.1186/1550-2783-6-6
38. Gualano B, de Salles Painelli V, Roschel H, et al. Creatine supplementation does not impair kidney function in type 2 diabetic patients: A randomized, double-blind, placebo-controlled, clinical trial. Eur J Appl Physiol. 2011;111:749–756. doi: https://doi.org/10.1007/s00421-010-1682-z
39. Neves M Jr, Gualano B, Roschel H, et al. Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women. Appl Physiol Nutr Metab. 2011;36:419–422. doi: https://doi.org/10.1139/h11-019
40. Carvalho APPF, Molina GE, Fontana KE. Creatine supplementation associated with resistance training does not alter renal and hepatic functions. Rev Bras Med Esporte. 2011;17:237–241. doi: https://doi.org/10.1590/S1517-86922011000400007
41. Lugaresi R, Leme M, de Salles Painelli V, et al. Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? J Int Soc Sports Nutr. 2013;10:26. doi: https://doi.org/10.1186/1550-2783-10-26
42. Hayashi AP, Solis MY, Sapienza MT, et al. Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: A randomized, double-blind, placebo-controlled, crossover trial. Lupus. 2014;23:1500–1511. doi: https://doi.org/10.1177/0961203314546024
43. Chilibeck PD, Candow DG, Landeryou T, Kaviani M, Paus-Jenssen L. Effects of creatine and resistance training on bone health in postmenopausal women. Med Sci Sports Exerc. 2015;47:1587–1595. doi: https://doi.org/10.1249/MSS.0000000000000576
44. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators; Kieburtz K, Tilley BC, Elm JJ, et al. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: A randomized clinical trial. JAMA. 2015;313:584–593. doi: https://doi.org/10.1001/jama.2015.120
45. Lobo DM, Tritto AC, da Silva LR, et al. Effects of long-term low-dose dietary creatine supplementation in older women. Exp Gerontol. 2015;70:97–104. doi: https://doi.org/10.1016/j.exger.2015.07.010
46. Pereira RT, Dorr FA, Pinto E, et al. Can creatine supplementation form carcinogenic heterocyclic amines in humans? J Physiol. 2015;593:3959–3971. doi: https://doi.org/10.1113/JP270229
47. Blancquaert L, Baguet A, Bex T, et al. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: A randomised trial. Br J Nutr. 2018;119:759–770. doi: https://doi.org/10.1017/S0007114518000471
48. Domingues WJR, Ritti-Dias RM, Cucato GG, et al. Does creatine supplementation affect renal function in patients with peripheral artery disease? A randomized, double-blind, placebo-controlled, clinical trial. Ann Vasc Surg. 2020;63:45–52. doi: https://doi.org/10.1016/j.avsg.2019.08.027
49. Sales LP, Pinto AJ, Rodrigues SF, et al. Creatine supplementation (3 g/d) and bone health in older women: A 2-year, randomized, placebo-controlled trial. J Gerontol A Biol Sci Med Sci. 2020;75:931–938. doi: https://doi.org/10.1093/gerona/glz177
50. Roschel H, Hayashi AP, Fernandes AL, et al. Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial. Clin Nutr. 2021;40:4849–4858. doi: https://doi.org/10.1016/j.clnu.2021.07.006
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Copyright (c) 2025 Mateusz Matczak, Karol Jasiński, Aleksandra Broda, Kacper Hoksa, Krzysztof Jodłowski, Ewa Dubniewicz, Paula Majewska, Alicja Staszek, Wiktoria Łoskot, Jan Szwech
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