Proceedings of The Physiological Society
University College London 2006 (2006) Proc Physiol Soc 3, PC7
Adaptation of iron absorption in the 5/6 nephrectomy animal model reflects the pathological features of chronic renal failure in humans
Nita Solanky1, Joanne Marks1, Robert J Unwin1, Edward S Debnam1, Surjit K Srai1
1. Epithelial Transport and Cell Biology Group, Departments of Physiology, Nephrology and Biochemistry, Royal Free & University College Medical School, London, United Kingdom.
Anaemia is present in the majority of patients with chronic renal failure (CRF) and is caused predominately by the lack of adequate erythropoietin (EPO) secretion. Patients treated with erythropoietin often require iron supplementation; however, oral iron therapy is not always effective, indicative of inadequate iron absorption in CRF. This present study investigated the effect of renal failure and EPO treatment on intestinal iron absorption in vivo, using the 5/6 nephrectomy model. Male Sprague-Dawley rats (240g) underwent a 2-stage, 5/6 nephrectomy or sham operation under halothane anesthesia (2-3% halothane in 100% oxygen). Analgesic (Rimadyl, 5mg/kg s.c.) was administered immediately after surgery and after a further 6 hours and the well being of the animals monitored daily. Animals were administered 100 i.u./kg recombinant human EPO or saline i.p. twice per week. After 5 weeks, animals were anaesthetised with pentobarbitone sodium (50mg/kg i.p.) and the femoral artery cannulated. Segments of duodenum (5cm beginning 1cm from the stomach) were selected and flushed with warm 0.9% saline, followed by air. Uptake buffer (250µl) containing 200µM iron labelled with 59Fe was instilled into the lumen and the segment was tied off. Blood (0.3ml) was collected at 5, 10, 15 and 30 min intervals and iron absorption calculated from the 59Fe activity of the uptake buffer and blood. Induction of renal failure was established by measurement of packed cell volume (PCV) and plasma urea and creatinine concentration. Animals that had undergone a 5/6 nephrectomy had a reduced PCV and increased plasma urea and creatinine concentration compared to sham operated animals, confirming induction of CRF. Intestinal iron absorption was significantly decreased in nephrectomised animals. EPO treatment normalized PCV, although, iron absorption was only partially restored (Fig. 1). These results suggest that changes in intestinal iron absorption in the 5/6 nephrectomy model reflect those occurring in patients with CRF, demonstrating this to be an appropriate model for investigating the underlying mechanisms of iron homeostasis in CRF.
Where applicable, experiments conform with Society ethical requirements