A randomized trial of intravenous iron supplementation and exercise on exercise capacity in iron-deficient non-anemic patients with chronic kidney disease

Abstract

Introduction Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity.

Methods Prospective, multicenter double-blind randomized controlled trial of non-dialysis patients with CKD and iron deficiency but without anemia (Hemoglobin (Hb)>110 g/l). Patients assigned (1:1): intravenous (IV) iron therapy, or placebo. An 8-week exercise programme commenced at week 4. Primary outcome was mean between-group difference in six-minute walk test (6MWT) at 4 weeks. Secondary outcomes included: 6MWT at 12 weeks, Transferrin Saturation (TSAT), serum ferritin (SF), hemoglobin (Hb), renal function, muscle strength, functional capacity, quality of life and adverse events at baseline, 4, 12 weeks. Mean between-group differences were analysed using ANCOVA models.

Results Among 75 randomized patients, mean (SD) age for iron therapy (n=37) vs placebo (n=38) was 54(16) vs. 61(12) yrs; eGFR [34(12) vs. 35(11)ml/min/1.73m2], TSAT [23(12) vs. 21(6)]%; SF [57(64) vs. 62(33)]μg/L; Hb [122.4 (9.2) vs. 127 (13.2)g/L]; 6MWT [384 (195) vs. 469 (142)metres] at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (p<0.02), and Hb at 12 weeks (p=0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy.

Conclusion This trial didn’t demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in non-dialysis patients with CKD who are iron-deficient.

Trial Registration EudraCT: 2018-000144-25 Registered 28/01/2019.