TY - JOUR
T1 - A randomized trial of intravenous iron supplementation and exercise on exercise capacity in iron-deficient non-anemic patients with chronic kidney disease
AU - Greenwood, Sharlene A.
AU - Oliveira, Benjamin A
AU - Asgari, Elham
AU - Ayis, Salma
AU - Baker, Luke A
AU - Beckley-Hoelscher, Nick
AU - Goubar, Aicha
AU - Banerjee, Debasish
AU - Bhandari, Sunil
AU - Chilcot, Joseph
AU - Burton, James O
AU - Kalra, Philip A
AU - Lightfoot, C.J
AU - Macdougall, Iain C
AU - McCafferty, Kieran
AU - Mercer, Thomas H.
AU - Okonko, Darlington O
AU - Reid, Chante
AU - Reid, Fiona
AU - Smith, Alice C.
AU - Swift, Pauline A.
AU - Watson, Emma
AU - Wheeler, David C.
AU - Wilkinson, Thomas J
AU - Bramham, Kate
N1 - Funding Information:
This was an investigator-led multicenter double-blind randomized placebo-controlled trial of patients with stages 3 to 4 CKD and iron-deficiency, but without anemia, aged 18 or over. The study design, flow of participants through the trial and methods have previously been reported. 21 The trial was funded by Kidney Research UK and supported by an unrestricted grant from Vifor (with donation of ferric carboxymaltose for the trial). Brent Ethics Committee approved the protocol (19/LO/0128) and the study was prospectively registered (EudraCT: 2018-000144-25 on 28/01/2019).
Funding Information:
The authors acknowledge the work of the various research teams at each site. The trial was funded by Kidney Research UK and supported by an unrestricted grant from Vifor (with donation of ferric carboxymaltose for the trial). The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, Kidney Research UK, or the Department of Health. The funders had no role in the design, collection, analysis, interpretation of the data, or writing of this protocol. Findings from the study will be disseminated at national and international conferences. All baseline data generated or analyzed during this study are included in this published article. The protocol and related documents were approved by Brent Research Ethics Committee, UK (REC) 19/LO/0128, the Health Research Authority and the UK Medicines and Healthcare products Regulatory Agency (MHRA). The study was prospectively registered on 28/01/2019 (EudraCT 2018-000144-25). All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects and/or their legal guardian(s). Authorship followed ICMJE guidelines. SG, DO, NB, FR, EW, TW, AS, and ICM were responsible for the inception and design of the project and prepared the manuscript. SG, NB, EA, JC, KM, DO, AM, SB, JB, ICM, PK, CR, PS, DB, DW, CL, LB, BO, KB, FR, SA, TM, AM, AG contributed to the design of the study, provided methodological input, and wrote the manuscript text and prepared tables. All authors reviewed the manuscript.
Publisher Copyright:
© 2023 International Society of Nephrology
PY - 2023/5/9
Y1 - 2023/5/9
N2 - 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 m
2], 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.
AB - 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 m
2], 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.
UR - http://www.scopus.com/inward/record.url?scp=85162259957&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2023.05.002
DO - 10.1016/j.ekir.2023.05.002
M3 - Article
SN - 2468-0249
VL - 8
SP - 1496
EP - 1505
JO - Kidney International Reports
JF - Kidney International Reports
IS - 8
ER -