Intravenous ferric carboxymaltose and exercise capacity in iron-deficient kidney transplant recipients: a randomised, placebo-controlled trial in the Netherlands.

Background: Whether correction of iron deficiency improves functional outcomes after kidney transplantation is unknown. We evaluated intravenous ferric carboxymaltose for improving exercise capacity in iron-deficient kidney transplant recipients. Methods: In this multicentre, double-blind, randomised, placebo-controlled trial, adult kidney transplant recipients with iron deficiency (ferritin <100 μg/L or 100-299 μg/L with transferrin saturation <20%) at least six months post-transplantation were recruited at two Dutch university hospitals between 7 October 2019 and 16 February 2024. Participants were assigned (1:1) to four intravenous doses of 500 mg ferric carboxymaltose or placebo at six-week intervals. The primary outcome was the between-group difference in 24-week change in 6-min walk test distance. Secondary outcomes included cardiac, kidney, muscle and cognitive function and quality of life. Efficacy was analysed by assigned treatment in 148 participants, with a per-protocol sensitivity analysis; safety analyses included 154 dosed participants. The trial was registered at ClinicalTrials.gov (NCT03769441). Findings: Of 155 participants randomised, seven were withdrawn under a prespecified COVID-19 amendment, leaving 148 participants for analysis (ferric carboxymaltose, n = 75; placebo, n = 73). Baseline 6-min walk test distance was 515 ± 91 m and 510 ± 114 m, respectively. Ferric carboxymaltose did not improve 6-min walk test distance versus placebo (adjusted mean difference +9 m [95% CI -10 to +28]). Ferric carboxymaltose corrected iron deficiency and increased haemoglobin, but did not improve cardiac function, muscle mass or strength, cognitive performance, or quality of life. Exploratory between-group differences occurred in estimated glomerular filtration rate and fibroblast growth factor 23. Infections and other clinically relevant adverse events did not differ between groups. Interpretation: Ferric carboxymaltose did not improve exercise capacity or most secondary outcomes, arguing against routine supplementation to improve functional capacity. Future studies should investigate observed differences in kidney function and fibroblast growth factor 23 concentrations and long-term clinical outcomes. Funding: Dutch Kidney Foundation, Dutch Heart Foundation, CSL Vifor.