Abstract: TH-PO486

Iron Therapy Modifies Oxidative Stress in Uraemic Cardiomyopathy

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular


  • Nuhu, Faisal, University of Hull, HULL, United Kingdom
  • Sturmey, Roger G, Hull York Medical School , Hull, United Kingdom
  • Seymour, Anne-Marie L, University of Hull, HULL, United Kingdom
  • Bhandari, Sunil, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, East Yorkshire, Hull, United Kingdom

Uraemic cardiomyopathy (UCM) is characterised by cardiac hypertrophy (LVH), metabolic remodelling and mitochondrial dysfunction, key factors in the development of heart failure (HF). Anaemia and oxidative stress are closely associated with LVH. Thus, the co-existence of both factors in chronic kidney disease (CKD) may aggravate progression to HF and increase the risk of sudden cardiac death. The aim of this study was to characterise oxidant status and iron deficiency (ID) anaemia in animal model of UCM; and determine the impact of intravenous (IV) iron therapy.


Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy, parenteral iron injected intravenously at week 6 (10mg/Kg body weight) and studies conducted 12 weeks post-surgery. Oxidative stress was evaluated through pro-oxidant enzyme activities and anti-oxidant capacities and levels of thiobarbituric acid-reactive substances (TBARS) in UCM. The extent of uraemia, anaemia and iron status was determined by serum biochemistry. Cardiac, renal and skeletal iron content was measured by inductively coupled plasma atomic emission spectroscopy.


The induction of uraemia resulted in LVH (HW/TL ratio (g/cm): 0.38 ± 0.01 vs 0.34 ± 0.01; p < 0.05); ID (serum iron (µM): 31.11 ± 1.80 vs 46.38 ± 1.44; p < 0.01), low total iron binding capacity (TIBC (µM): 26.43 ± 0.72 vs 29.46 ± 0.83; p < 0.05) and anaemia (haematocrit (%): 42.5 ± 3 vs 55.0 ± 3; p < 0.05); reduced systemic glutathione peroxidase (GPx) activity ((U/ml): 1.12 ± 0.11 vs 1.48 ± 0.12; p < 0.05). Oxidative stress in UCM was further evidenced by elevated cardiac GSSG/GSH ratio, TBARS and activities of pro-oxidant enzymes. IV iron therapy had little effect on LVH but caused repletion of hepatic iron stores, improved anaemia and systemic GPx activity. In turn, iron supplementation ameliorated oxidative stress in the heart by enhancing anti-oxidant defence system without any significant impact on the kidney. Therapy also improved oxidant status in both skeletal and hepatic tissues.


Iron therapy improved the anti-oxidant defence system and consequently oxidant status of cardiac and skeletal muscles. These data highlighted the benefits of managing ID anaemia in the early stages of CKD to reduce vulnerability to oxidative stress and may lessen associated adverse cardiovascular outcomes.


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