HEALTH EFFECTS OF FERRIC CARBOXYMALTOSE SUPPLEMENTATION IN IRON-DEFICIENT KIDNEY TRANSPLANT RECIPIENTS: RESULTS OF A RANDOMIZED CONTROLLED TRIAL

Iron deficiency (ID) affects ±30% of kidney transplant recipients (KTR). In previous observational studies in KTR, ID was independently associated with poor quality of life and cognitive functioning and a higher risk of all-cause and cardiovascular mortality. In chronic heart failure, ID correction improves exercise capacity, cardiac function and quality of life; whether these effects also occur in KTR is unknown. The main objective of this trial was to address whether intravenous ferric carboxymaltose (FCM) improves exercise capacity in iron-deficient KTR. We also evaluated the effects on a broad range of parameters of cardiac, kidney and muscle function, cognitive performance and quality of life.

We performed a 24-week, double-blind, multicenter, randomized, placebo-controlled trial evaluating the efficacy of FCM in stable KTR with ID (plasma ferritin <100 μg/L or ferritin 100-299 μg/L with transferrin saturation (TSAT) <20%). Participants were assigned to four doses of FCM (500 mg Fe3+/dose) or placebo, with six-week intervals. The primary end point was the change in six-minute-walk-test (6MWT) distance between baseline and week 24. Secondary outcomes included changes in iron status and hemoglobin, mineral metabolism, estimated GFR (combined creatinine-cystatin C 2021 CKD-EPI), muscle mass and strength (24-hour urinary creatinine excretion, Timed Up-and-Go test, handgrip strength and five-times sit to stand test), echocardiographic assessment of cardiac structure and function, cognitive performance (neuropsychological assessment) and quality of life (SF-36, EuroQol-5D-5L and other questionnaires).

We included 148 iron-deficient KTR (median age 57 (interquartile range 47-66) y, 68% male, time since transplant 2 (1-7) y, hemoglobin 13.2±1.3 g/dL, ferritin 47 (27-71) µg/L, TSAT 20±10%, eGFR 61±18 mL/min/1.73 m2). At baseline, 6MWT distance was 515±91 meters in the FCM arm and 510±114 meters in the placebo arm. The 6MWT distance improved both in the FCM (+21±53 m vs. baseline) and placebo arm (+19±50 m, P=0.42 between groups, Fig 1A); changes were not significantly different among subgroups (Fig 1B). FCM increased ferritin, TSAT and hemoglobin (Fig 1C-E) and reduced plasma total (FCM: -77±117 RU/mL; placebo: +38±185 RU/mL, P<0.001) and intact FGF23 levels (FCM: -20±87 pg/mL; placebo: +10±79 pg/mL, P=0.01). FCM also led to a small reduction in plasma phosphate levels (FCM: -0.05±0.17 mmol/L; placebo: -0.01±0.16 mmol/L, P=0.04). There was no effect on 24-hour urinary phosphate excretion, plasma or urinary calcium or parathyroid hormone levels. FCM increased eGFR (FCM: +1.7±6.3 ml/min/1.73 m2; placebo: -0.9±6.5 mL/min/1.73m2, P<0.001, Fig 1F). FCM also improved the Timed Up-and-Go test (FCM: -0.1±0.7 s; placebo: +0.1±1.2 s, P=0.02, Fig 1G), a measure of functional mobility, but not other measures of muscle mass and strength. It also did not improve cardiac structure and function, cognitive performance, or quality of life. No increased risk of infections or other relevant side effects was observed in the FCM arm.

In kidney transplant recipients, correction of iron deficiency with FCM did not improve exercise capacity or cardiac structure and function, compared with placebo. However, FCM may improve functional mobility and kidney function. FCM was well tolerated in the population under investigation.