Iron deficiency, with and without anaemia, across strata of kidney function in kidney transplant recipients

Ayerdem, Gizem; Hassel, Gaston van; Vinke, Joanna Sophia J; Kremer, Daan; Gaillard, Carlo A. J. M.; Borst, Martin H. de; Bakker, Stephan J. L.; Eisenga, Michele F.

doi:10.1093/ndt/gfab173

Cited by 3 publications

(2 citation statements)

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“…Open access after transplantation. [5][6][7][8][9] ID has been associated with an increased risk of mortality in KTRs, independent of coexisting anaemia. 5 Iron is involved in oxygen transport as a component of haemoglobin.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 98%

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Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

Vinke

Eisenga²,

Sanders³

et al. 2023

BMJ Open

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IntroductionIron deficiency (ID) is common and has been associated with an excess mortality risk in kidney transplant recipients (KTRs). In patients with chronic heart failure and ID, intravenous iron improves exercise capacity and quality of life. Whether these beneficial effects also occur in KTRs is unknown. The main objective of this trial is to address whether intravenous iron improves exercise tolerance in iron-deficient KTRs.Methods and analysisThe Effect of Ferric Carboxymaltose on Exercise Capacity after Kidney Transplantation study is a multicentre, double-blind, randomised, placebo-controlled clinical trial that will include 158 iron-deficient KTRs. ID is defined as plasma ferritin <100 µg/L or plasma ferritin 100–299 µg/L with transferrin saturation <20%. Patients are randomised to receive 10 mL of ferric carboxymaltose (50 mg Fe3+/mL, intravenously) or placebo (0.9% sodium chloride solution) every 6 weeks, four dosages in total. The primary endpoint is change in exercise capacity, as quantified by the 6 min walk test, between the first study visit and the end of follow-up, 24 weeks later. Secondary endpoints include changes in haemoglobin levels and iron status, quality of life, systolic and diastolic heart function, skeletal muscle strength, bone and mineral parameters, neurocognitive function and safety endpoints. Tertiary (explorative) outcomes are changes in gut microbiota and lymphocyte proliferation and function.Ethics and disseminationThe protocol of this study has been approved by the medical ethical committee of the University Medical Centre Groningen (METc 2018/482;) and is being conducted in accordance with the principles of the Declaration of Helsinki, the Standard Protocol Items: Recommendations for Interventional Trials checklist and the Good Clinical Practice guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Study results will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numberNCT03769441.

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Section: Strengths and Limitations Of This Studymentioning

confidence: 98%

“…Iron deficiency (ID) is common after kidney transplantation, with reported prevalences ranging between 11% and 47%, depending on the definition and time after transplantation 5–9. ID has been associated with an increased risk of mortality in KTRs, independent of coexisting anaemia 5.…”

Section: Introductionmentioning

confidence: 99%

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

Vinke

Eisenga²,

Sanders³

et al. 2023

BMJ Open

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Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity

van Hassel,

Rivrud,

Timmerman

et al. 2024

Open Heart

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BackgroundIron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population.Methods and resultsBlood count and haematological parameters were determined in plasma of 61 Fontan patients (51% female, mean age 29±9 years). ID was defined as transferrin saturation (TSAT) ≤19.8%. The prevalence of ID was 36% (22/61 patients). Especially among women, the diagnosis of ID was highly prevalent (52%) despite normal haemoglobin levels (153.7±18.4 g/L). Mean ferritin levels were 98±80 µg/L and mean TSAT levels were 22%±12%. Cardiopulmonary exercise testing was performed in 46 patients (75%). Patients with ID had a lower peak oxygen uptake (V̇O2peak) (1397±477 vs 1692±530 mL/min; p=0.039), although this relationship was confounded by sex. The presence of ID increased the likelihood of not achieving a respiratory exchange ratio (RER) ≥1.1 by 5-fold (p=0.035).ConclusionID is highly prevalent among patients with a Fontan circulation. V̇O2peak is lower in patients with ID. Fontan patients with ID are less likely to achieve an RER≥1.1 during cardiopulmonary exercise testing.

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A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents

Chienwichai,

Phirom,

Wuttiputhanun

et al. 2024

Syst Rev

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Background The effects of various risk and associated factors on post-kidney transplant anemia (PTA) have not been fully compared and estimated. This meta-analysis aims to elucidate factors contributing to PTA and determine the influence of erythropoietin-stimulating agents (ESAs) on renal outcomes, thus offering potential pathways for enhanced management strategies post-transplant. Methods A systematic review was conducted in electronical database. Studies reporting on risk factors (with cause-effect relationships) and associated factors (without definite cause-effect relationships) of PTA, and the effects of ESAs on post-kidney transplant outcomes, were included. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were analyzed using random-effects models. Results This systematic review encompassed 38,233 patients from 85 studies. Factors increased PTA risk included African American, older donor age, human antigen leukocyte mismatches, and low pre-transplant hemoglobin levels. Poor allograft function, high interleukine-6, Cytomegalovirus , delayed graft function, allograft rejections, immunosuppressive medications, and renin-angiotensin system blockades were associated with PTA. Native autosomal dominant polycystic kidney disease was a protective factor against PTA. Administration of ESAs with the aim of normalizing hemoglobin levels in patients with chronic allograft dysfunction slowed the decline in eGFR and reduce the risk of death, with a pooled OR of 0.36 (95% CI : 0.14 to 0.89; p = 0.040). Conclusions The risks and associated factors for PTA have been elucidated, underscoring the need for individualized treatment approaches. Late ESA therapy, aimed at hemoglobin normalization, suggests a renal-protective effect and reduced mortality, which should be considered in the management of PTA. Systematic review registration PROSPERO CRD42024545330. Supplementary Information The online version contains supplementary material available at 10.1186/s13643-024-02709-8.

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Iron deficiency, with and without anaemia, across strata of kidney function in kidney transplant recipients

Cited by 3 publications

References 14 publications

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity

A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents

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