Response of patients with sickle cell anaemia and end-stage renal disease to erythropoietin treatment.

Sir,

Generally, end-stage renal disease (ESRD) due to sickle cell anaemia (SCA) occurs in <1% of patients receiving renal replacement treatment. For this reason, data about this patient group are very limited and controversial. Both the unresponsiveness of erythropoietin (Epo) treatments and their positive effects for extending the blood transfusion intervals of such patients were previously reported in studies with only one to three patients [1-3]. In this study, the responses of eight patients with concurrent SCA and ESRD to Epo treatment were retrospectively investigated.

A total of eight patients (four males, four females; mean age, 42 ± 11.7 years) with ESRD and SCA who were followed up between May 2001 and October 2009 were studied, including one pre-dialysis (Stage 4–5), two peritoneal dialysis and five haemodialysis patients. During the study period, one patient died and one patient was transferred to another centre after renal transplantation. The data of the patients were obtained from the patient records and routine monthly dialysis recordings. Unscheduled haemoglobin measurements recorded in the emergency room during painful episodes and control haemoglobin levels measured after transfusions were recorded but not included in the calculations. The means of the haemoglobin and ferritin levels, transferrin saturation indices, blood transfusion requirements and hospitalizations were recorded before and after Epo treatment over a period of 12 months. The results of pre- and post-Epo treatment were compared using the paired t-test.

In four haemodialysis patients, treatment with epoetin beta had been started after blood transfusions when haemoglobin levels rose to approximately 7–8 g/dL, with a dosage of 75 U/kg/week. Despite this therapy, haemoglobin concentrations fell to 5–5.5 g/dL in 2 months. Therefore, the epoetin beta dosage was increased to and maintained at 150 U/kg/week. The other four patients were both started and maintained on Epo therapy at the upper end of the dosage range allowed for ESRD patients, according to guidelines. Haemoglobin levels of all the patients were recorded throughout the study period while they were under the maximum maintenance Epo dosage with the following results: 0.75 μg/kg/week s.c. for darbepoetin alpha (one pre-dialysis and two peritoneal dialysis patients) and 150 U/kg/week s.c. for epoetin beta (five haemodialysis patients). No patient was receiving iron therapy and only one patient received the hydroxyurea treatment with an adjusted ESRD dose (500 mg/day) during the study period.

There was no significant difference between the means of the haemoglobin (5.6 ± 0.4 vs 5.5 ± 0.4 g/dL) and ferritin levels (>2000 vs >2000 ng/mL), transferrin saturation indices (72.6 ± 19.5 vs 76.5 ± 21.2%), numbers of hospitalizations (5.5 times per year—min. 3, max. 8 vs 6.0 times per year—min. 2, max. 9) and blood transfusion needs and rates (minimum 1–2 U/2–3 months, maximum 1–3 U/1–2 months) before and after Epo treatment. The haemoglobin levels of the patients still decreased to between 4.0 and 4.5 g/dL once or twice during the year Epo was being administered (Table 1). There was no newly developed thromboembolic event in any of the patients during Epo treatment.

Table 1

Characteristics of SCA and ESRD patients and summary of Epo response

Patient number	Patient characteristics1	Epo type and dose (s.c.)	Hb, pre-Epo (g/dl)	Hb, on Epo (g/dl)	Minimum Hb, on Epo (g/dl)2	Blood transfusion need and rate pre-Epo	Blood transfusion need and rate on Epo
1	32 years, M, HD	Epoetin beta, 3 × 5000 U/week	6.4	5.9	4.0	16 U/year, 1–3 U per 1–2 M	17 U/year, 1–3 U per 1–2 M
2	41 years, M, HD	Epoetin beta, 2 × 5000 U/week	5.7	5.6	4.2	10 U/year, 1–2 U per 1–2 M	11 U/year, 1–2 U per 1–2 M
3	33 years, M, HD	Epoetin beta, 3 × 4000 U/week	5.1	6.2	4.5	9 U/year, 1–2 U per 2 M	8 U/year, 1–2 U per 2 M
4	43 years, F, PD	Darbepoetin alpha, 50 μg/week	5.4	5.5	4.4	13 U/year, 1–2 U per 1–2 M	12 U/year, 1–2 U per 1–2 M
5	53 years, F, PD	Darbepoetin alpha, 60 μg/week	5.6	5.3	4.5	11 U/year, 1–2 U per 2 M	11 U/year, 1–2 U per 2 M
6	65 years, F, HD	Epoetin beta, 2 × 5000 U/week	6.1	5.7	4.3	14 U/year, 1–3 U per 1–2 M	15 U/year, 1–3 U per 1–2 M
7	38 years, M, HD	Epoetin beta, 3 × 5000 U/week	5.3	5.2	4.0	12 U/year, 1–3 U per 1–2 M	12 U/year, 1–3 U per 1–2 M
8	31 years, F, Stage 4–5	Darbepoetin alpha, 40 μg/week	5.6	5.2	4.5	8 U/year, 1–2 U per 2 M	9 U/year, 1–2 U per 2 M

U, units; M, months.

Age, gender (male/female), haemodialysis (HD), peritoneal dialysis (PD).

Minimum haemoglobin recorded in emergency room.

Epo treatment was continued (14 ± 2.2 months) in one pre-dialysis and two peritoneal dialysis patients and was ceased in five patients due to unresponsiveness to treatment. In one of the patients in whom Epo treatment was ceased, the treatment had been administered from May 2001 to September 2006, ceased in 2006 and the patient died in 2008. The mean time of Epo treatment in the other four patients in whom Epo had been stopped due to unresponsiveness was 18 ± 6.3 months.

In this retrospective study, the unresponsiveness of Epo treatment, resulting in target haemoglobin levels not being reached in patients with concurrent SCA and ESRD, could possibly be due to the fact that the precise cause of anaemia in this patient group is not Epo insufficiency. On the other hand, since basal endogenous Epo levels in SCA patients are shown to be higher than in the normal population, the Epo requirement may also be much higher than for other ESRD patients following the development of renal failure [4].

With regard to the variable individual response to Epo treatment, until more precise data are available, with a higher number of patients with SCA and ESRD from different centres, it would be appropriate to attempt treatment with the maximum possible dose for a period and then to stop this expensive treatment if the expected response cannot be achieved.

Conflict of interest statement. None declared.