#2938 The association between serum iron biomarkers and health-related quality of life in patients undergoing dialysis
Authors: Mahic Osman , van Lieshout Thomas Sebastiaan , Vernooij Robin Wm , Van Jaarsveld Brigit , Abrahams Alferso 
Published: May 2024

Abstract

Background and Aims
Anemia is a very common complication of chronic kidney disease, affecting most patients undergoing dialysis. Iron deficiency, one of the causes of anemia, is generally a second consideration in the management of anemia. Nephrologists mainly focus on the correction of hemoglobin, often prescribing iron therapy for this indication only. However, iron has important physiological functions besides erythropoiesis. Conversely, iron overload can lead to oxidative stress and cellular damage. Therefore, nephrologists have been cautious to prescribe iron therapy to patients with already high serum iron levels. This caution has been underscored by studies linking higher levels of iron to increased mortality. Unfortunately, evidence is lacking regarding the impact of iron on important patient-reported outcomes like health-related quality of life (HRQoL). Therefore, the aim of this study is to explore the association between serum iron biomarkers, health-related quality of life (HRQoL) and the presence of anemia-related symptoms over a one-year period in patients undergoing dialysis.

Method
Data were obtained from the multicenter, prospective, observational Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). Adult patients new to dialysis were included, and had a baseline and follow-up assessments at 3, 6 and 12 months, with measurements of serum iron biomarkers ferritin and transferrin saturation (TSAT). HRQoL, encompassing physical and mental HRQoL, was measured using the validated 12-item Short Form Health Survey (SF12, summary scores ranging from 0 to 100). The presence of anemia-related symptoms: fatigue, shortness of breath, restless legs and muscle cramps were assessed using the Dialysis Symptom Index. Patients were categorized into 4 groups depending on their ferritin levels (μg/L): &lt;200, 200–500 (reference), &gt;500–700 and &gt;700, and into 3 groups depending on their TSAT levels (%) at baseline: &lt;20, 20–39 (reference), and ≥40. Longitudinal analyses were conducted using sequential conditional mean models to adjust for time-independent and time-varying confounding. All analyses captured the overall association over a one-year follow-up.

Results
We included 1069 patients, of whom 76% started hemodialysis, the median age was 68, 66% were male, and 32% were receiving iron therapy. Over a one-year follow-up, patients with ferritin &lt;200 μg/L had similar physical HRQoL (MD=0.5 ; 95% CI –2.4 to 3.3 ) and mental HRQoL (MD=0.04 ; 95% CI -2.0 - 2.0) compared to the reference group with ferritin between 200–500 μg/L. Patients with ferritin between 501–700 μg/L also had a similar physical and mental HRQoL mental HRQoL compared to those with ferritin between 200-500 μg/L. This was also found for patients with ferritin above 700 μg/L (Fig. 1). Similarly, patients with TSAT levels below 20% and patients with TSAT levels ≥40% had comparable physical and mental HRQoL compared the reference group of patients with a TSAT between 20-39% (Fig. 2). For the secondary objectives, we found no significant differences in the anemia-related symptoms fatigue, shortness of breath, restless legs, or muscle cramps between patients with various levels of ferritin nor between the various TSAT groups.

Conclusion
We found that dialysis patients with higher or lower levels of ferritin or TSAT did not have a significantly different physical or mental HRQoL over a one year-follow up after starting dialysis. Similarly, no significant differences were found in the presence of fatigue, shortness of breath, restless legs, and muscle cramps between patients with these higher or lower levels of serum iron markers. And although iron levels do have impact on clinical outcomes such as mortality, these results suggest that they do not influence patient reported outcomes such as physical and mental HRQoL.