Iron Deficiency Linked to Poor Outcomes in Kidney Transplant Recipients

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Iron deficiency, independent of anemia, may be a potentially modifiable target to improve patient-reported outcomes after kidney transplantation.

Iron deficiency, independent of anemia, was strongly associated with more fatigue, worse major depressive symptoms, and lower health-related quality of life (HRQoL) scores in kidney transplant recipients, according to new research.1

These associations remained in a fully adjusted model, suggesting the clinical importance of iron deficiency for improving patient-reported outcomes (PROs) in kidney transplant recipients, independent of hemoglobin levels.

“The observed effect sizes for the associations of iron deficiency with patient-reported outcomes evoke interest, and shed light on the potential impact that iron deficiency may have in kidney transplant recipients, regardless of co-existing anemia,” wrote the investigative team led by Daan Kremer, MD, division of nephrology, department of internal medicine, University Medical Center Groningen.

Improvements in patient survival after kidney transplantation have led credence to the concept of “life after transplantation” beyond graft and patient survival. However, kidney transplant recipients experience more psychosocial symptoms, such as fatigue, depression, and anxiety symptoms, than the general population, impairing their HRQoL.

Anemia is a well-recognized cause of poor HRQoL outcomes in kidney transplant recipients, with iron deficiency being a primary cause of the condition. Iron deficiency, increasingly recognized as a potential target to safely improve patient outcomes in kidney transplant recipients, is often underrecognized in current nephrology practice.

Current guidelines do not explicitly endorse iron status assessment in the absence of anemia. A recent KDIGO statement underlined the need for further research on the connection between anemia, iron status, and HRQoL. In the current analysis, Kremer and colleagues evaluated the association of iron deficiency with patient-reported outcomes in kidney transplant recipients, accounting for the potential mediating role of anemia.

Cross-sectional data were obtained from the ongoing, single-center, prospective TransplantLines Biobank and Cohort Study. Since June 2015, all solid organ transplantation patients and living donors from the investigator’s institution have been invited to participate. This analysis included outpatient kidney transplant recipients (≥1-year post-transplantation) with available iron status parameters and HRQoL assessment.

Psychosocial factors, including individual strength attributes, well-being, anxiety, and symptoms of depression, were assessed in the analysis. HRQoL was assessed using validated forms of the Short Form 36 (SF-36) and EuroQol Five-Dimensions 3-level (EQ5D-3L) questionnaires. For the primary analysis, iron deficiency was defined according to global guidelines: TSAT <20% and ferritin <100 µg/L.

Overall, 814 kidney transplant recipients (62% male; age, 56 years) were enrolled in the study, at a median of 3 years after transplantation. Of this population, 229 (28%) kidney transplant recipients had iron deficiency and 237 (29%) were anemic; 84 (10%) patients had both iron deficiency and anemia.

Upon analysis, iron deficiency was independently associated with an increased risk of severe fatigue (odds ratio [OR], 1.66; 95% CI, 1.10 - 2.51; P = .016), being at risk for sick leave or work disability (OR, 1.62; 95% CI, 1.15 - 2.29; P = .006), anxiety symptoms (OR, 1.51; 95% CI, 1.04 - 2.18; P = .028), and major depressive symptoms (OR, 2.14; 95% CI, 1.21 - 3.77; P = .009). Iron deficiency was also independently associated with a lower ability to concentrate. These results were independent of age, sex, estimated glomerular filtration rate (eGFR), anemia, and other potential confounders.

By contrast, anemia was not associated with any of these outcomes. In the fully adjusted logistic regression model, iron deficiency was associated with an estimated 53% higher risk of severe fatigue (P = .050), a 100% higher risk of major depressive symptoms (P = .018), and a 51% higher chance of being at risk for sick leave or work disability (P = .022).

Further adjusted analyses on HRQoL revealed iron deficiency was independently associated with lower physical component scores (P = .006), mental component scores (P = .013), health status assessed using a visual analog scale (P = .004), and lower health status derived from the utility score (P = .010). Once more, investigators found no association of anemia with these outcomes.

Sensitivity analysis with hemoglobin on a continuous scale, rather than anemia, led to similar results as the primary analyses. Kremer and colleagues found the associations between iron deficiency and outcomes remained mostly unchanged after adjustment for hemoglobin instead of anemia.

“Effect modification analyses showed no interaction of hemoglobin on the associations, further supporting that iron deficiency is associated with psychosocial symptoms and lower HRQoL regardless of hemoglobin level,” investigators wrote.


  1. Kremer D, Knobbe TJ, Vinke JSJ, et al. Iron deficiency, anemia, and patient-reported outcomes in kidney transplant recipients. Am J Transplant. Published online March 15, 2024. doi:10.1016/j.ajt.2024.03.017
  2. van Sandwijk MS, Al Arashi D, van de Hare FM, et al. Fatigue, anxiety, depression and quality of life in kidney transplant recipients, haemodialysis patients, patients with a haematological malignancy and healthy controls. Nephrol Dial Transplant. 2019;34(5):833-838. doi:10.1093/ndt/gfy103
  3. Babitt JL, Eisenga MF, Haase VH, et al. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2021;99(6):1280-1295. doi:10.1016/j.kint.2021.03.020