Published in the Journal of Nephropathology in 2012, Iranian nephrologists reported a case of a previously healthy 32-year-old man with no pre-existing kidney disease who developed interstitial nephritis (inflammation of kidney tissue) two weeks after beginning creatine monohydrate supplementation for bodybuilding.

The patient presented with elevated creatinine and reduced kidney function. Kidney biopsy confirmed interstitial nephritis. His kidney function improved after discontinuing creatine and beginning corticosteroid treatment. No other causes of the nephritis were identified, and the temporal relationship strongly suggested creatine as the trigger.

While case reports cannot prove causation and are the weakest form of evidence, they document that kidney injury associated with creatine use does occur in some individuals. This case is particularly concerning because the patient had no known risk factors and was taking creatine at commonly recommended doses.

Published in Pediatric Nephrology in 2025, Canadian nephrologists reported a 17-year-old male who developed acute kidney injury with cast nephropathy following a standard 6-day high-dose creatine loading regimen.

The patient presented with bilateral flank pain and kidney enlargement. Importantly, he was well-hydrated and showed no markers of rhabdomyolysis (muscle breakdown), which is the mechanism typically blamed for creatine-related kidney problems. Kidney biopsy confirmed cast nephropathy, a condition where protein deposits block kidney tubules.

This was the first reported case of creatine-induced cast nephropathy in a well-hydrated adolescent, representing a novel injury mechanism that cannot be prevented by the standard advice to "drink plenty of water." The case raises questions about whether adolescent kidneys may respond differently to creatine loading than adult kidneys, and highlights that novel injury mechanisms may still be discovered despite decades of research.

Published in Frontiers in Nutrition in 2018, sports science researchers Andrew Jagim and Chad Kerksick conducted a review specifically examining the evidence base for creatine safety in active adolescents and youth.

They found that no published study has been designed with a primary objective to examine creatine safety in adolescents. All safety data for this age group comes from studies with other primary endpoints or from extrapolation of adult data. Despite this evidence gap, 21% of boys aged 14-18 report using creatine supplements.

Product labels commonly warn that those under 18 should not use creatine, but this warning lacks scientific basis and exists purely as a legal precaution. The effects of creatine-induced increases in intramuscular water and muscle volume during the critical puberty growth period (when bones, tendons, and joints are developing) are not understood. The authors called for dedicated safety trials in adolescent populations.

Published in Food Chemistry in 2011, Italian researchers analyzed 33 commercially available creatine supplement products for contaminants, comparing them to EFSA safety limits.

Of the 33 products tested, 44% exceeded 100 mg/kg of creatinine contamination. Approximately 15% exceeded EFSA limits for dihydrotriazine (>4.5 mg/kg) and dicyandiamide (>50 mg/kg). Dihydrotriazines are structurally related to known carcinogenic compounds, though their specific toxicity in humans has not been established. Mercury was detected in some product samples.

This study demonstrates that not all creatine products on the market meet the safety specifications assumed in clinical research. Most safety studies use pharmaceutical-grade creatine (like Creapure, 99%+ purity), but consumers often purchase cheaper products with unknown purity. The gap between studied products and marketed products means that real-world safety may be lower than what clinical trials suggest.

In 2004, the European Food Safety Authority''s Scientific Panel on Food Additives issued an opinion on creatine monohydrate for use in foods for particular nutritional uses. While accepting creatine for use, they raised several safety concerns about contaminants.

EFSA noted that dicyandiamide (a common manufacturing contaminant in creatine) may be converted to hydrogen cyanide by stomach acid. They also noted that dihydrotriazines (another class of contaminants) are structurally related to known carcinogenic compounds, though specific human toxicity data are lacking. EFSA set maximum limits for these contaminants but acknowledged the data gaps.

Critically, EFSA has not established a safe upper daily intake limit for creatine supplementation. This is unusual for a substance with such widespread use and contrasts with other nutrients and supplements where upper limits are defined. The absence of an upper limit reflects not that any amount is safe, but that EFSA deemed the available data insufficient to determine one.

Published in BMJ Case Reports in 2014, clinicians documented a case where creatine ethyl ester supplementation elevated serum creatinine levels sufficiently to produce a clinical picture mimicking chronic kidney disease on standard laboratory tests.

The elevated creatinine triggered the estimated GFR calculation to indicate kidney impairment, despite the patient having completely normal actual kidney function. The abnormalities reversed upon discontinuation of creatine supplementation, confirming they were artifactual rather than pathological.

This diagnostic confounding problem has practical safety implications: creatine users who undergo routine blood work may be misdiagnosed with kidney disease, leading to unnecessary anxiety, additional invasive testing (kidney biopsies), or withholding of medications that are cleared through the kidneys. The authors warned clinicians to always ask about supplement use before interpreting elevated creatinine results, but this advice is inconsistently followed in practice.

Published in the Journal of the American Board of Family Medicine in 2006, physicians reviewed case reports linking creatine supplementation to rhabdomyolysis (severe muscle breakdown that can cause kidney failure).

Six cases were documented where individuals developed rhabdomyolysis while using creatine. In one case, a college football player taking 10 g/day developed rhabdomyolysis after surgery, with creatine kinase (CK) levels peaking at 194,000 U/L (normal is under 200 U/L). While the role of creatine versus exercise, surgery, or dehydration as the primary cause remained unclear in most cases, the review concluded that creatine may be a contributing factor.

The review recommended that creatine supplementation is contraindicated in individuals with pre-existing renal disease or those taking nephrotoxic medications. It also noted that creatine users who engage in intense exercise in hot environments may face elevated rhabdomyolysis risk compared to non-users, as creatine increases intramuscular water retention and may alter muscle cell vulnerability under extreme stress.

Published in the Journal of the American Society of Nephrology in 2006, Mayo Clinic physicians reported a healthy 24-year-old male weight lifter who developed acute renal failure with proteinuria while taking creatine monohydrate alongside multiple other bodybuilding supplements.

Kidney biopsy showed acute interstitial nephritis. While the specific causal contribution of creatine versus the other supplements could not be determined, the case illustrates an important gap in the safety literature: clinical trials test creatine in isolation under controlled conditions, but real-world users frequently "stack" multiple supplements simultaneously.

The safety of creatine in combination with pre-workouts, protein powders, BCAAs, testosterone boosters, and other common bodybuilding supplements has not been systematically studied. Given that approximately 50% of gym-goers take multiple supplements simultaneously, the clinical trial evidence may underestimate real-world risks by studying a context that does not match actual consumer behavior.