Multiple daily doses of oral iron supplementation best for improving hemoglobin levels in anemia and chronic kidney disease
Presenter: Nilang G. Patel, MD, Virginia Commonwealth University, Richmond, VA
Effect of multiple doses per day vs daily vs alternate-day oral iron therapy in iron deficiency anemia with CKD. Abstract TH-O986. Presented Nov 2, 2023.
Three different oral iron supplement strategies—daily, multidose per day, and alternate-day dose—improve hemoglobin (Hgb) and iron indices in patients with iron deficiency anemia and chronic kidney disease (CKD); however, a multidose per day strategy improved indices the most at 90 and 180 days. The typical strategy employed in clinical practice is administration of oral iron two to three times per day.
“In this large cohort study of veterans with iron deficiency anemia with CKD, multiple doses per day oral iron strategy significantly improved hemoglobin compared to daily or alternate-day oral iron supplementation,” concluded the investigators, led by Nilang G. Patel, MD, Virginia Commonwealth University, Richmond, VA. “In multiple doses per day strategy, delta change in hemoglobin value from baseline were much larger than daily and alternate-day oral iron supplementation group at 90 and 180 days.”
They conducted a retrospective observational study of 24,476 veterans with iron deficiency anemia (Hgb < 12 g/dL plus either iron saturation of < 20% or ferritin < 50 µg/L), and CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2). They received the first index outpatient prescription of oral iron for 90 days with 1 additional refill within 120 days.
Some 95.4% of the study group were male, more than 90% were older than 60 years (median age: 74.57 years), three-fourths had a body mass index greater than 25 kg/m2, 50.9% to 54.5% were taking an ACE inhibitor or angiotensin-receptor blocker, and about 60% in each dosing strategy group had diabetes. The mean eGFR ranged from 42.41 (alternate-day dose group) to 43.96 mL/min/1.73 m2 (multidose per day group). About one-third in each group had chronic obstructive pulmonary disease, and 42.5% (alternate-day dose group) and 47.1% (multidose per day group) had heart failure. A Charlson Comorbidity Index greater than 3 was recorded in 57.4% (multidose per day group) and 66.4% (alternate-day dose group).
The multidose per day strategy improved indices at a fastest pace. The median number of days until a 1 g/dL increase in HgB was 92 in the daily dose group, 89 in the multidose per day group, and 92 in the alternate-day dose group (P < .001 for multidose group vs other two groups).
A linear mixed-effects model showed that Hgb improved significantly from baseline (0.006 g/dL/day, P < .001) in the daily dose group. In comparison to that group, those in the multidose per day group had greater improvements (plus 0.002 g/dl/day, P < .001); there was less improvement observed in the alternate-day dosing group (minus 0.001 g/dL/day, P = .02). Improvements in ferritin and serum iron saturation ratios were similar but did not show any statistical difference between the daily and the alternate-day dosing groups.
At 90 days, improvements in HgB levels from baseline were 0.71 g/dL (95% CI, 0.68-0.73) in the daily dose group, 0.99 g/dL (95% CI, 0.97-1.01) in the multidose per day group, and 0.63 g/dL (95% CI, 0.52-0.73) in the alternate-day dose group. At 180 days, levels improved by 1.27 g/dL (95% CI, 1.24-1.31), 1.75 g/dL (95% CI, 1.72-1.77), and 1.09 g/dL (95% CI, 0.95-1.24), respectively.
Mean improvements in ferritin levels at 90 and 180 days were as follows:
- 10.0 (95% CI, 7.04-12.96) and 19.31 ng/mL (95 CI, 14.65-23.96) in the daily dose group
- 21.24 (95% CI, 18.76-23.71) and 40.66 ng/mL (95% CI, 36.81-44.50) in the multidose per day group
- 8.67 (95% CI, minus 2.69-20.03) and 13.95 ng/mL (95% CI, minus 5.31-33.21) in the alternate-day dose group.
Mean reductions in total iron-binding capacity levels at 90 and 180 days were as follows:
- 17.20 (95% CI, 18.79-15.61) and 33.69 (95% CI, 36.36-31.01) mg/dL with daily dosing
- 31.34 (95% CI, 32.69-29.99) and 59.43 (95% CI, 61.66-57.20) mg/dL with multidoses per day
- 12.07 (95% CI, 17.89-6.24) and 22.15 (95% CI, 32.35-11.95 mg/dL) with alternate-day dosing.
Mean improvements in iron stores by serum iron saturation ratio (%) at 90 and 180 days were as follows:
- 6.36 (95% CI, 6.09-6.62) and 11.54 (95% CI, 11.07-12.00) in the daily dose group
- 7.76 (95% CI, 7.53-8.00) and 14.24 (95% CI, 13.84-14.65) in the multidose per day group
- 6.94 (95% CI, 5.99-7.89) and 12.27 (95% CI, 10.53-14.01) in the alternate-day dose group.
The difference in improvement of Hgb levels between daily and alternate-day oral iron supplementation strategy was statistically significant “but with marginal clinical significance at 90 and 180 days,” according to the investigators.
They concluded that “the choice of oral iron therapy should depend on the rapidity of response desired and patient preference due to adverse effects.”
The authors declared no relevant conflicts of interest.
https://www.asn-online.org/education/kidneyweek/2023/program-abstract.aspx?controlId=394292