Can Acidosis and Hyperphosphataemia Result in Increased Erythropoietin Dosing in Haemodialysis Patients?

Aim: To evaluate whether factors such as acidosis and hyperphosphataemia that might cause an increased oxygen delivery to tissues could result in increased dosing requirements for intravenous erythropoietin (EPO) administration given to haemodialysis patients.

Methods: The clinical records of the patients seen at the Hypertension, Nephrology, Dialysis and Transplantation Clinic from December, 2004 through August, 2005 were reviewed to identify patients who had taken intravenous erythropoietin. Two-tailed, Pearson's correlation was performed to determine correlations between any of the parameters. Analysis of variance and stepwise regression for covariance were used to evaluate the relations of demographic and clinical characteristics and laboratory variables. Analysis of covariance and K means cluster analyses were also performed to examine linkage between variables. Kendall's Tau correlation was used for correlations of non-parametric data.

Results: There was a significant direct or positive correlation at the 0.01 levels between dry weight, age, intact parathyroid hormone level (PTH), and serum phosphorus and EPO dose. There was an inverse or negative correlation at that level between the serum bicarbonate and urea reduction ratio (URR) with the EPO dose at the same level while there was a weaker correlation but direct correlation between the white blood count (WBC) and EPO dose. There was significant colinearity between serum phosphorus and PTH but serum phosphorus showed a more significant correlation with EPO overall. Stepwise regression analysis for covariance revealed that phosphorus remained significantly correlated with EPO resistance after the removal of the effect of PTH while PTH lost its significance after the effect of phosphorus was removed.

Conclusion: Acidosis and hyperphosphataemia are associated with apparent increased erythropoietin dosing requirements. While this study did not evaluate the mechanism of such requirements and indeed many mechanisms might be possible, a rightward shift in the oxygen-haemoglobin dissociation curve resulting in down-regulation of erythropoietin receptors is considered consistent with the data and present knowledge.