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Intradialytic Creatine Supplementation in Hemodialysis

By the CreatineIQ Research Desk
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 strongly 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 is a safe and feasible method of administration, generally well-tolerated by patients.
  • Dose-Dependent Increases: Higher concentrations of creatine in the dialysate led to significantly larger increases in pre-dialytic intra-erythrocytic (within red blood cells) creatine concentrations.
  • 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 study establishes the safety profile necessary for larger trials to test if restoring creatine levels improves mortality and quality of life in hemodialysis patients.

The Study Design

The study included 16 hemodialysis patients (aged 27-78) 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.

The Findings

The study demonstrated that intradialytic supplementation raises creatine inside red blood cells in a dose-dependent way. 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.

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 a highly accurate picture of systemic cellular uptake.

Limitations

As a pilot study, the sample size was very small (16 patients), which limits the statistical power and generalizability of the findings. Furthermore, while the study proved that creatine levels can be restored, it did not measure whether this restoration actually translated into functional benefits (like improved muscle strength or quality of life).

Conflicts of Interest

One of the authors (Theo Wallimann) is a member of the Advisory Board of Crearene. The remaining authors declared no conflicts of interest, and the funder had no role in the conduct of the trial.

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 dose-dependent way. 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. It measured whether creatine levels could be raised, not whether raising them makes patients feel better or live longer — 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.