Thrice-Weekly Iron Pills Match Daily Dosing in Dialysis Patients, 18-Year Audit Finds

People with kidney failure who rely on peritoneal dialysis often struggle with anemia, and the iron pills prescribed to correct it can pile up into a daily pill burden that many patients find hard to tolerate. A retrospective study from a single Dutch dialysis center found that hemoglobin and iron status trajectories over six months were similar in patients taking oral iron three times a week and those taking it once daily, though the authors note the modest sample size and observational design limit how far the findings can be generalized.

Using linear mixed-effects models to handle the irregular, real-world timing of laboratory measurements, the researchers found that hemoglobin trajectories in the three-times-weekly group were statistically indistinguishable from those in the once-daily group, with a P value of 0.30 for the group-by-time interaction. Ferritin, a marker of stored iron, and transferrin saturation, a measure of iron available for red blood cell production, also followed similar paths in both groups. The authors suggest that less frequent dosing may reduce treatment burden without compromising hematologic outcomes, while cautioning that the study did not directly measure iron delivery.

The rationale for less frequent dosing comes from hepcidin physiology. When oral iron is absorbed, the liver rapidly produces hepcidin, a hormone that blocks further iron uptake from the gut and traps iron inside storage sites.

Interestingly, the twice-daily regimen told a different story. Patients on twice-daily dosing started with significantly lower baseline hemoglobin levels, about 1.22 grams per deciliter below the once-daily group, but their hemoglobin rose more steeply over time, gaining an additional 0.013 grams per deciliter per day compared with once-daily dosing, a difference that was highly statistically significant. They caution that without direct hepcidin measurements, any mechanistic explanation remains speculative.

The three-times-daily regimen, prescribed mainly between 2012 and 2016 to only seven patients, showed no significant differences from once-daily dosing in any of the measured parameters. The small size of this group, like the seven-patient three-times-weekly group, limits the statistical power of the comparisons, and the authors emphasize that the findings cannot be directly generalized to clinical decision-making without larger, randomized studies.

The first sensitivity analysis, which adjusted for age, sex, erythropoiesis-stimulating agent dose, and inflammation, yielded results comparable to the primary analyses, while a second analysis restricted to incident iron users was exploratory and underpowered. When the researchers adjusted for age, sex, erythropoiesis-stimulating agent dose, and inflammation, using leukocyte count as a proxy because C-reactive protein data were sparse, the estimated differences between regimens remained essentially unchanged. A second sensitivity analysis restricted to patients who started iron supplementation only after beginning peritoneal dialysis produced more variable results, but the group sizes in that analysis were so small, ranging from two to five patients per regimen, that the authors describe those findings as exploratory and underpowered.

Beyond comparing regimens, the audit uncovered a striking gap in care. Among 30 peritoneal dialysis patients who received no iron supplementation at all during their dialysis period, nine, or 30 percent, met the contemporaneous Dutch guideline criteria that would have recommended a trial of iron therapy. Fourteen of these untreated patients had previously been on hemodialysis, and eight of them had received iron during that earlier period but were never restarted after switching to peritoneal dialysis.

The descriptive data also hinted at different patterns of iron handling between regimens. The three-times-weekly group showed rising hemoglobin alongside a marked increase in transferrin saturation and only modest ferritin gains, a pattern the authors interpret as iron being preferentially channeled into red blood cell production rather than storage. The once-daily group, by contrast, showed pronounced ferritin increases with smaller transferrin saturation changes and no corresponding hemoglobin rise, suggesting more iron was being deposited in stores. The authors urge caution in over-reading these descriptive comparisons, since they did not account for treatment switches and the groups were small.

The authors note that reduced dosing frequency lowers pill burden and may improve tolerability, though they emphasize that these observational findings cannot be directly applied to clinical decision-making. Oral iron therapy frequently causes gastrointestinal side effects, and in peritoneal dialysis patients constipation is a particular concern because it can impair dialysis function. The authors call for an expert consensus process, such as a Delphi exercise, to address the evidence gaps and better define optimal iron supplementation strategies for this population, incorporating inflammatory markers, hepcidin measurements, and patient-reported outcomes.

Subject of Research: Comparison of oral ferrous fumarate dosing regimens for anemia management in peritoneal dialysis patients

Article Title: Oral ferrous fumarate dosing regimens in peritoneal dialysis: a single-center retrospective audit

Article References: Tijs, A. M., Rawee, P., Yang, Y., Manson, N. A., Hazenberg, I. T., Westerhuis, R., Abrahams, A. C., Nolte, I. M., & Eisenga, M. F. (2026). Oral ferrous fumarate dosing regimens in peritoneal dialysis: a single-center retrospective audit. Frontiers in Nephrology, 6, Article 1989068. https://doi.org/10.3389/fneph.2026.1989068

Image Credits: AI Generated

DOI: 10.3389/fneph.2026.1989068

Keywords: peritoneal dialysis, oral iron supplementation, ferrous fumarate, anemia, hemoglobin, ferritin, transferrin saturation, hepcidin, chronic kidney disease, retrospective cohort study, dosing frequency, iron deficiency