A proposal of the simple guide regarding the conversion ratio from epoetin to darbepoetin alpha in treating haemodialysis patients with renal anaemia.

Sir,

Darbepoetin alpha (darbepoetin), which has the longest half-time of all the erythropoiesis-stimulating agents (ESAs), is now used world-wide with many advantages for both the patient and the healthcare worker [1,2]. Several recent observations have suggested that in treating renal anaemia the conversion ratio from epoetin to darbepoetin according to the theoretically calculated ‘1 μg darbepoetin = 200 U epoetin’ rule (1:200 rule) leads to an overestimate of the required darbepoetin dose [1]. In particular, in a large-scale multicentre prospective study of 100 haemodialysis (HD) patients, Bock et al. concluded that, although the 1:200 rule is appropriate for lower epoetin doses (<5000 IU/week), a 1:250 to 1:350 conversion rule could be applied to the darbepoetin dose for patients converting from ≥5000 IU of epoetin per week [1]. I almost agree with their conclusion. But I think that a simpler guide regarding the conversion ratio according to the proceeding epoetin dose could be obtained from my experience of treating HD patients with darbepoetin for over 7 months in our clinic and I will attempt to propose the guide here.

In our clinic, 32 chronic HD patients underwent HD treatment two to three times a week in September 2007 and I took charge of all the patients at that time and remained in charge of them thereafter. Out of these patients 26 had been treated with between 750 and 9000 IU of epoetin alpha (epoetin) weekly for renal anaemia. I changed all these patients to darbepoetin from October, the 40th week in 2007. I estimated adequate initial dose of darbepoetin according to the 1:200 rule and 10, 15, 20, 30 or 40 μg of darbepoetin was given once a week or every two weeks to these patients. My policy to treat renal anaemia is basically by the combination of ESAs and iron repletion without other medication, and the target level of haemoglobin (Hb) of the patients is almost between 10 and 11 g/dL according to the guidelines in 2004 of the Japanese Society for Dialysis Therapy [3]. Though several changes in the doses were required in many patients during about the first 12 weeks, almost adequate doses of darbepoetin needed to keep Hb stable could be obtained after that.

Those HD patients who developed anaemia from other causes than renal failure, such as intestinal bleeding, during the previous 12 weeks, were excluded for the evaluation.

Finally, 23 out of the 26 patients were eligible for this inquiry. I reviewed their clinical records and found the total epoetin doses of each individual patient from the 4 weeks between week 32 and 35 in 2007 as well as the Hb levels from weeks 32 and 36. In the same way, I got the total darbepoetin doses from the 13th to the 16th week in 2008 and got Hbs at the 15th and the 17th week. From these data, I calculated individual patient's weekly doses of epoetin per 1.0 g/dL of Hb during the former 4 weeks and also calculated weekly darbepoetin doses per 1.0 g/dL of Hb during the latter 4 weeks. Then, I compared the doses of epoetin with the ones of darbepoetin for 1.0 g/dL of Hb in each individual patient to get the darbepoetin:epoetin conversion ratio.

Only one patient belonging to the epoetin > 6000 IU/ week group showed darbepoetin:epoetin = 1:631, five patients in the 6000 IU/week ≥ epoetin > 4500 IU/week group showed a mean ratio of 1:303 (1:401, 318, 289, 282, 227), nine patients in the 4500 IU ≥ epoetin > 3000 IU group showed 1:251 (1:379, 356, 274, 260, 248, 243, 209, 151, 139) and eight patients in the 3000 IU ≥ epoetin group showed 1:169 (1:305, 265, 211, 146, 133, 113, 97, 81).

From these results, I think the individual difference in the adequate conversion ratio is very noticeable in the lower epoetin doses (≤3000 IU) group and we should take this fact into consideration at the change of the ESAs. Though I admit that in this inquiry the number of subjects is too small to reach a definite conclusion, I believe the results show a similar, but partially more remarkable, tendency to the one by Bock et al. [1]. And I should apply their conclusion to my original guide mentioned below, particularly in the higher epoetin doses group (>6000 IU/week) because of insufficient number of subjects.

I would like to propose a simple guide regarding the initial conversion ratio from epoetin to darbepoetin according to the proceeding epoetin dose in treating haemodialysis patients with renal anaemia. The ratios from epoetin to darbepoetin are 1:350 in proceeding epoetin doses > 6000 IU/week, 1:300 in 6000 IU/week ≥ epoetin > 4500 IU/week, 1:250 in 4500 IU/week ≥ epoetin > 3000 IU/week and 1:200 in epoetin ≤3000 IU/week. Of course, after the conversion, we should continue to control darbepoetin doses carefully, at least for several months, until a stable target Hb can be kept.

Conflict of interest statement. None declared.