The clinical significance of aldosterone in ESRD: Part II

Sir, I would like to thank Lars Weiss for his interesting comments regarding my Editorial Comment [1] from over a year ago! However, I do have some difficulty accepting one or two of his arguments. While one cannot completely exclude the possibility of different pharmacodynamics between epoetin alfa and epoetin beta, I feel it is unlikely that a difference in intravenous (i.v.) half-life of 6.8±2.7 h for i.v. epoetin alfa and 8.8±2.2 h for i.v. epoetin beta, along with 19.4±10.7 h for subcutaneous (s.c.) epoetin alfa and 24.2±11.2 h for s.c. epoetin beta [2] can really make a substantial difference to biological activity. There may be other differences between epoetin alfa and epoetin beta previously unrecognized, but it would be surprising if such subtle differences in pharmacokinetics in a study conducted in healthy volunteers translated into an enhanced clinical efficacy. However, I do accept completely Weiss’s comment that inclusion criteria including only iron-replete and welldialysed patients should be ‘regarded as standard in trials of dialysis patients’. As I said in my Editorial Comment [1], and in a follow-up Reply Letter [3], it is always difficult to extrapolate results from scientific studies into everyday clinical practice. While one cannot criticize the inclusion criteria in either the Swedish [4] or Italian [5] studies, the experience of Jones et al. [6] and Geddes and Woo [7] testify to this. I also disagree with Weiss’s comment that a Kt/V of >1 and a ferritin level of >200mg/l are the ‘norm’ in dialysis units; I accept the unpublished data from the Swedish Society of Nephrology, but it is well known that Sweden boasts some of the best results in renal anaemia management in Europe (as reported in the ESAM survey [8]), and the experience in other countries in Europe falls far short of the results that Weiss quotes. Thus, I still feel that we should be cautious about extrapolating results from wellcontrolled clinical trials into everyday clinical practice in our dialysis units. Finally, although half-lives aren’t everything, before getting too excited about a possible difference between 19.4 and 24.2 h for s.c. administration of epoetin alfa and epoetin beta, respectively, one should not forget that the half-life for s.c. darbepoetin alfa is substantially greater at 48.8±12.7 h [9].