Discussion
CKD, myotoxicity, fatigue, cardiomyocite damage, pain, kidney dysfunction, Phosphaturia
CARDIOVASCULAR DISEASE, KIDNEY DYSFUNCTION, IRON DEFICIENCY, OXIDATIVE STRESS, SECONDARY, IRON DEFICIENCY ANEMIA, HEART FAILURE, PHOSPHATURIA
The “Iron and Phosphaturia – ExplorIRON-CKD” study has demonstrated a trend for improvement in quality of life and functional status following administration of intravenous iron. A significant improvement in the whole cohort was seen in terms of physical function, energy, emotional role limitation, and pain using the results of the SF-36, alongside a significant improvement in functional status and fatigue as delineated by 1-min-sit-to-stand test and FSS visual analogue scale respectively. Intravenous iron did not lead to any detrimental effect on surrogate markers of cardiac strain and cardiomyocite damage, whilst some beneficial result was noted on vascular function/arterial stiffness.As suggested by Strauss and Auerbach, fatigue resolution is best monitored through a combination that allows the investigation of a continuum between vitality and fatigueFunctional status improved as indicated through the 1-min-sit-to-stand test scores. Similar to quality of life, the baseline scores achieved were lower than the ones previously reported in literature relevant to CKD, potentially noting the effect of iron deficiency anemiaCardiovascular markers including NT-proBNP and Troponin T remained stable throughout the trial and was similar in both groups. Previous studies related to ND-CKD and iron deficiency have noted a non-significant decrease in NT-proBNP following intravenous iron administration (1000 mg FDI) (baseline: 422.5 (881.9) pg/mL to 1-month: 242.5 (209.1) pg/mL)The results of the present trial are also in agreement with previously published evidence pertaining to vascular function following administration of intravenous iron in patients with ND-CKD. Such trends highlight a potential mechanistic safety despite concerns regarding oxidative stress and endothelial damage. A previous pooled analysis has noted no worsening in PWV(cf) or Augmentation Index following administration of 1000 mg FDI in ND-CKDThis trial had several limitations including a small number of participants with no ethnic minority groups and therefore generalizability of the results is not possible. In addition, the possibility of errors upon completion of the questionnaires provided cannot be excluded. The small numbers may represent the reason behind the lack of any differential effect noted. In addition, certain differences between the two groups at baseline may account for the lack of significant findings of the DASI scores or the differential effect in terms of FSS scores. Indeed participants in the FCM arm were significantly older with prolonged QRS complexes and greater incidence of heart failure. It is also possible that detection of significance within the FCM group was hindered by its small size. Moreover, the trial took place throughout the COVID-19 pandemic which was characterized by higher psychological stress in patients with CKDNevertheless, the “Iron and Phosphaturia – ExplorIRON-CKD” was a double-blind randomized controlled trial, providing valuable results for direct future research. The results are suggestive of improvement in functional status and quality of life following intravenous iron infusion. To our knowledge, this is the first trial to have provided evidence supporting the notion of intravenous iron administration leading to 1-min-sit-to-stand test improvement in patients with ND-CKD and iron deficiency anemia. In addition, this exploratory study is the first to compare to two modern intravenous iron in patients with advanced kidney dysfunction (median eGFR 18 mL/min/1.73 mAs part of the secondary outcome analysis of the current trial, no significant differential effect was noted in quality of life measures, functional status and cardiovascular biomarkers. An improvement was witnessed in most domains of the Short-Form (36) questionnaire, fatigue status, and 1-min-sit-to-stand ability increased significantly by the end of the trial in whole population. These results provide further evidence on the neutrality of modern intravenous iron compounds in terms of cardio and myotoxicity and potential benefit in terms of functional status. This is important clinically, as CKD and iron deficiency anemia are considered risk factors to cardiovascular disease, with prior concerns rending iron as a pro-oxidant substance. These concerns may explain previous publication results suggesting persistent under-dosing in patients with CKD requiring intravenous iron, therefore potentially limiting the benefit that could be obtained by accurate supplementation