A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD

Sharlene A Greenwood; Benjamin A Oliveira; Elham Asgari; Salma Ayis; Luke A Baker; Nicholas Beckley-Hoelscher; Aicha Goubar; Debasish Banerjee; Sunil Bhandari; Joseph Chilcot; James O Burton; Philip A Kalra; Courtney J Lightfoot; Iain C Macdougall; Kieran McCafferty; Thomas H Mercer; Darlington O Okonko; Chante Reid; Fiona Reid; Alice C Smith; Pauline A Swift; Anastasios Mangelis; Emma Watson; David C Wheeler; Thomas J Wilkinson; Kate Bramham

doi:10.1016/j.ekir.2023.05.002

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD

Kidney Int Rep. 2023 May 9;8(8):1496-1505. doi: 10.1016/j.ekir.2023.05.002. eCollection 2023 Aug.

Authors

Sharlene A Greenwood^{1

2}, Benjamin A Oliveira², Elham Asgari³, Salma Ayis², Luke A Baker⁴, Nicholas Beckley-Hoelscher², Aicha Goubar², Debasish Banerjee⁵, Sunil Bhandari⁶, Joseph Chilcot², James O Burton⁴, Philip A Kalra⁷, Courtney J Lightfoot^{4

8}, Iain C Macdougall^{1

2}, Kieran McCafferty⁹, Thomas H Mercer¹⁰, Darlington O Okonko², Chante Reid¹, Fiona Reid², Alice C Smith^{4

8}, Pauline A Swift¹¹, Anastasios Mangelis², Emma Watson⁴, David C Wheeler¹², Thomas J Wilkinson^{4

13}, Kate Bramham^{1

2}

Affiliations

¹ King's College Hospital NHS Trust, London, UK.
² King's College London, London, UK.
³ Guy's and St Thomas' NHS Trust, London, UK.
⁴ University of Leicester, Leicester, UK.
⁵ St George's University Hospitals NHS Foundation Trust, London, UK.
⁶ Hull University Teaching Hospitals NHS Trust, UK.
⁷ Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK.
⁸ National Institute of Health Research Leicester Biomedical Research Center, Leicester, UK.
⁹ Barts Hospitals NHS Trust, London, UK.
¹⁰ Queen Margaret University, Edinburgh, UK.
¹¹ Epsom and St Helier University Hospitals NHS Trust, London, UK.
¹² University College London, London, UK.
¹³ National Institute of Health Research, Applied Research Collaboration East Midlands, Leicester, UK.

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 of nonanemic patients with CKD who have iron-deficiency.

Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models.

Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m²], 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 [95] vs. 469 [142] meters) 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 did not 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 nondialysis patients with CKD who are iron-deficient.

Keywords: Iron; chronic kidney disease; exercise; fatigue; muscle metabolism; physical activity.