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Intradialytic Creatine Supplementation in Hemodialysis

By the CreatineIQ Research Desk
Last reviewed
New Research
Renal
Clinical Trial

Patients undergoing hemodialysis are particularly vulnerable to creatine deficiency. This is caused by a combination of impaired endogenous synthesis by the kidneys and the continuous loss of creatine during the dialysis process itself. This deficiency is associated with a lower health-related quality of life and a higher risk of mortality.

A 2026 double-blind, randomized, placebo-controlled pilot study sought to determine whether administering creatine directly into the dialysate (intradialytic supplementation) could safely and effectively raise systemic creatine levels in these patients.

Key Takeaways

  • Feasibility and Safety: Intradialytic creatine supplementation appeared feasible and was generally well tolerated in this small pilot, with no serious adverse events.
  • Dose-Dependent Increases: Higher concentrations of creatine in the dialysate produced larger increases in pre-dialytic intra-erythrocytic (within red blood cells) creatine concentrations, in what the authors describe as a pattern consistent with a dose-dependent effect.
  • Plasma Levels Less Clear-Cut: Plasma creatine showed an overall treatment effect (p = 0.002), but every individual dose group's confidence interval crossed zero — so the red-blood-cell result is much firmer than the plasma one.
  • Foundation for Future Research: This pilot provides preliminary feasibility and tolerability data for a larger trial to test whether restoring creatine levels improves mortality and quality of life in hemodialysis patients. Its secondary measures of strength, physical function and quality of life did not change, but it was not designed to detect such effects.

The Study Design

The study enrolled 19 hemodialysis patients, 16 of whom (aged 27-78) completed it; dropouts were replaced. Patients were enrolled across four sequentially initiated groups. Each group received a fixed creatine concentration in their dialysate (0.5, 1.0, 1.5, or 2.0 mmol/L). Within each group, patients were randomized in a 3:1 ratio to receive either the creatine-enriched dialysate or a standard placebo dialysate.

The intradialytic creatine was administered over a 6-week period. The primary outcomes measured were the changes in pre-dialytic intra-erythrocytic and plasma creatine concentrations. Secondary outcomes included hand grip strength, the Short Physical Performance Battery (SPPB), body composition by bioelectrical impedance, lung function (FEV1), hand dexterity and health-related quality of life (the SF-36 questionnaire).

The Findings

The study found that intradialytic supplementation raised creatine inside red blood cells, in what the authors describe as a pattern consistent with a dose-dependent effect. At 6 weeks, the three higher dose groups showed increases in pre-dialytic intra-erythrocytic creatine whose confidence intervals excluded zero: +685 µmol/L (95% CI +17 to +1352) at 1.0 mmol/L, +1146 (+431 to +1766) at 1.5 mmol/L, and +1098 (+431 to +1766) at 2.0 mmol/L. The lowest dose, 0.5 mmol/L, did not reach that bar: +399 (−269 to +1066).

The plasma results deserve more caution than the headline suggests. While the overall treatment effect was statistically significant (p = 0.002), not one of the four individual dose groups produced a plasma increase whose confidence interval excluded zero — the changes were −16, +21, +119 and +163 µmol/L, every one spanning zero. The evidence that this method loads creatine into red blood cells is considerably stronger than the evidence that it raises circulating plasma creatine.

None of the secondary outcomes changed: the authors report no effect of the intervention on grip strength, SPPB, body composition, FEV1, hand dexterity or SF-36 quality of life. They note the study was not designed to detect changes in these measures and that six weeks is likely too short, and no formal power calculation was performed — so this is an absence of evidence rather than evidence of no effect.

On safety, no serious adverse events occurred, though one patient in the 1.5 mmol/L group dropped out due to a potential side effect.

Analyzing the Study: Strengths & Limitations

Strengths and Reputability

The study addresses a highly specific and clinically significant problem (creatine loss during dialysis) using a robust double-blind, placebo-controlled design. By measuring creatine levels both in plasma and inside red blood cells, the researchers obtained two complementary readouts. The authors use red-blood-cell creatine as a minimally invasive marker of tissue uptake, because red blood cells, like muscle cells, carry creatine transporters — though it remains an indirect marker, and red-cell creatine also varies with the age of the cells.

Limitations

As a pilot study, the sample size was very small (16 completers) and no formal power calculation was performed, which limits the statistical power and generalizability of the findings. Furthermore, while the study showed that intra-erythrocytic creatine can be raised this way, it cannot say whether that translates into functional benefits. Grip strength, physical performance, body composition, lung function, dexterity and quality of life were measured as secondary outcomes and did not change, but a six-week pilot of this size was neither designed nor powered to detect such effects.

Conflicts of Interest

The study's funding statement names one funder, Crearene AG: the University Medical Center Groningen received financial support from the Swiss company for this study. According to the paper, Crearene had no role in the initial study design or in writing the protocol, but reviewed and approved the final protocol, without requesting changes, before the study began; it had no role in the conduct of the study, data collection, analysis, interpretation or manuscript preparation. One of the authors (Theo Wallimann) is a member of the Advisory Board of Crearene. The remaining authors declared no conflicts of interest.

Conclusion

This 2026 pilot study does what a pilot study is supposed to do: it shows that delivering creatine through the dialysate is feasible, well tolerated, and capable of raising intra-erythrocytic creatine, in a pattern consistent with a dose-dependent effect. That is a real contribution to a patient group with few good options.

Its impact should be sized honestly, though. With 16 patients spread across four dose groups, roughly four patients per arm, this is a dosing and safety exercise rather than a test of benefit. Its secondary measures of strength, physical performance, body composition and quality of life showed no effect, but a six-week pilot of this size was not built to detect one, and it did not assess survival at all — the outcomes that would actually change care. The plasma findings are weaker than the red-blood-cell findings. The value here is that it clears the way for the larger randomised trial the authors call for, which is where the clinically meaningful question will be answered.

References

  1. Doorenbos CSE, van der Veen Y, Post A, et al. Feasibility, safety and tolerability of intradialytic creatine supplementation in hemodialysis: A double-blind, randomized, placebo-controlled pilot study. PLoS One. 2026;21(8):e0354883. doi:10.1371/journal.pone.0354883.