Association between haemoglobin and neopterin concentrations in haemodialysis patients treated with erythropoietin

To the Editor: Recombinant human erythropoietin (rHuEPO) is well established for treating anaemia in patients with renal failure. Erythropoietin (EPO) deficiency is a major mechanism of this type of anaemia because normally 90 % of EPO is produced in the kidney and EPO secretion is blunted when renal disease develops (1). In fact, rHuEPO treatment is capable of increasing haematocrit and haemoglobin levels in the majority of patients with chronic renal failure. Nevertheless, not all patients respond to rHuEPO nor respond to the same degree. In these cases, other or additional causes of anaemia such as infections or serum inhibitors have been implicated (2, 3). We have studied 34 patients (19 males, 15 females) mean age of 46 yr (range: 23-76) with chronic renal failure and on regular dialysis treatment with cuprophan membranes three times a week, for a time span of 4 h, during a mean of 31 months (range: 5-119). Except for 3 patients, all had haemoglobin levels below 120 g/l. Fifteen patients, who had haemoglobin lower than 80 g/1 before therapy, were treated with rHuEPO 2-3 times a week and with doses of 25-50 Ujkg each time. The median period of treatment was 4.5 months (range: 2-11). No patient was on therapy with immunosuppressive drugs and none had evidence of infectious disease at the time of study. Blood samples were obtained immediately before and after dialysis. rHuEPO was injected intravenously 15 min before the end of the dialysis. Serum EPO and neopterin concentrations were determined by radioimmunoassays (EPOTrac, Incstar Corp., Stillwater, MN, USA, and Henning, Berlin, GFR). Concentrations of serum iron were established by absorption at 562 nm wavelength of Fe-11-ferrozine-complex. Serum ferritin concentrations were quantified by Elisa (Boehringer, Mannheim, GFR). Comparison of groups was done by Mann Whitney U-test, Wilcoxon paired ranked test and Spearman rank correlation coefficients. In the whole group of 34 dialysis patients, haemoglobin concentration ranged from 64 to 136 g/l; 16 of 34 patients had levels above lOOg/l. Serum iron was 3.6-24.3 pmol/l (median: 11.2) and ferritin levels were 5-1372 pg/l (median: 110). EPO levels before dialysis ranged from 4 to 98 U/l (9 patients had EPO above the upper limit of normal which was found to be 31 U/l using the same assay; Ref. 4). Serum neopterin levels ranged from 15 to 634 nmol/l (upper limit of normal: 8.7) before dialysis. Mean ferritin levels (447 2 321 mg/l) were higher in patients treated with rHuEPO than in untreated patients (1 56 f 188). Haemoglobin levels of the EPO-treated patients (99 14 g/l) were higher (U = 3.38, p < 0.001) when compared to their pretreatment levels (69 +_ 9.2 g/l). In the patients, neopterin levels after dialysis were inversely correlated to haemoglobin (r, = 0.355, p < 0.05) and serum iron concentrations (r, = 0.384, ~ ~ 0 . 0 5 ) . In the group of rHuEPOtreated patients (n = 15) haemoglobin was inversely related to EPO (r, = 0.694, ~ ~ 0 . 0 1 ) and neopterin levels (r, = 0.544, ~ ~ 0 . 0 5 ) after dialysis. When patients from the EPO-treated group were split into two subgroups one with EPO levels after dialysis more than twice as high as compared to levels before dialysis (n = 9; EPO: 338 147 Ujl) and the other with lower EPO levels ( n = 6 ; EPO: 21 +_ 8 Ujl) significant differences of haemoglobin and neopterin levels after dialysis were observed (Fig. 1). Serum neopterin concentrations have previously been shown to be inversely correlated with haemoglobin in other types of anaemias, e.g., in patients with haematological and gynaecological malignancies (4, 5 , 6) and in human immunodeficiency virus infection (7). In addition, neopterin closely correlated to changes of iron metabolism in anaemia of these chronic disorders (4, 6, 7) , in which iron appears to be transferred from the circulation to storage sites. In these situations anaemia is related to