Novel haematological parameters in patients receiving recombinant human erythropoietin and undergoing haemodialysis

Abstract

Recombinant Human Erythropoietin (EPO) replacement therapy effectively treats the chronic anaemic associated with end stage renal disease. However due to an increase in demand, a functional iron deficiency state may arise which is characterised by an inability to supply iron and subsequent EPO resistance. Indicators of iron status are potentially misleading in this situation. Red cell ferritin (RCFer) and reticulocyte indices may be more reliable measures of functional iron deficiency. We investigated, prospectively, the value of RCFer and reticulocyte indices to detect functional iron deficiency in 11 patients, 10 male and 1 female, mean age 51 years (ranges 20-74) commencing subcutaneous EPO therapy. All patients had received oral ferrous sulphate 600 mg, total dose, daily for 6 weeks prior to starting EPO. Study subjects had a mean aluminium of 1.1 mmol/L (28.9 μg/L) and parathyroid hormone (PTH) 109 pg/L. Serum folate, vitamin B12 deficiencies and bleeding diathesis were excluded. Dialysis adequacy was maintained with a mean Kt/V (a measure of the amount of plasma cleared of urea divided by the urea distribution volume V) of 1.0 and urea reduction ratio of 64%. Haemoglobin rose from a mean value of 8.0-9.9 g/dl (p < 0.01). There was an associated significant fall in both serum ferritin (SF) (205.5-62.88 μg/l, p < 0.01) and RCFer (19.96-10.8 ag/red cell, p < 0.001). After 96 days of EPO therapy, 18% of patients had a demonstrably reduced RCFer (< 7 ag/red cell) whilst none had a reduced SF (< 15 μg/L) and 75% had a transferrin saturation (TS) < 20%. Mean SF levels remained consistently above 50 μg/L. There was no significant change in TS verifying its poor sensitivity as a marker of functional iron deficiency. Mean haemoglobin content of reticulocytes (CHr) and mean haemoglobin concentration of reticulocytes (CHCMr) fell (p < 0.001, p < 0.01 respectively) to levels suggesting iron deficiency at 3 months. These results suggest that RCFer and CHr may help detect the onset of functional iron deficiency in patients commencing EPO therapy despite oral iron. EPO therapy leads to a significant depletion of both erythroid and storage iron.