The aim of the study is to

1. To determine whether treatment with Erythropoiesis-stimulating agents (in the form of Aranesp®) affects platelet function, and how.
2. To determine whether salicylate treatment changes the effect of EPO (erythropoietin) on platelet function.

Background:

It is well known that treatment with EPO increases the risk of thrombotic complications in patients with chronic kidney disease, including cerebral thrombosis. The requited level of Hgb for sufficient treatment has therefore been set at a relatively low level (6.8-7.3 mM). One obvious potential cause of this problem is the increased thrombocytosis and platelet activation caused by EPO treatment. An old investigation has shown that low-dose acetyl salicylic acid (ASA) treatment can remove this effect. This investigation has not been performed using modern methods to investigate platelet function, and the possible prophylaxis of EPO-induced thrombosis has since received little interest.

Investigators of current study therefore propose to repeat this investigation using advanced methods for assessing thrombocyte function, as a preliminary, exploratory investigation prior to a later randomized controlled study.

Pre-treatment Washout (4 weeks, 6 weeks if treated with Mircera))

Patients who are not treated with ESA do not receive any treatment. Patients treated with ESA stop their treatment for 4 weeks. Patients treated with Mircera ® stop treatment for 6 weeks.

Patients must not take ASA as an analgesic during the whole period of the project.

At the end of the pre-treatment period, the Standard package (blood samples) is assessed.

EPO Treatment (4 weeks) The patient is treated with darbepoetin alfa (Aranesp) in equipotent doses compared to previous therapy.

After 2 weeks the Hgb is measured, and the EPO dosis adjusted if necessary at the discretion of the responsible physician.

After 4 weeks, the Standard package is assessed. If the Hgb is >8,0 mM or is rising rapidly (>1,2mM per month), the EPO dose is reduced at the discretion of the responsible physician.

EPO + ASA Treatment Aranesp treatment is supplemented with ASA (Hjertemagnyl ® 75 mg x 1 daily). After 4 weeks the Standard package is assessed.

If the patient develops gastrointestinal symptoms (abdominal pain, nausea or heartburn), and is not already being treated with pantoprazole or other PPI (proton pump inhibitors), treatment is supplemented with pantoprazole 40 mg x 1 daily.

ASA treatment withdrawal - e.g. in regard to surgery - results in discontinuation of participation in the study.

Post-treatment Washout Both Aranesp and Hjertemagnyl treatment is stopped. After 4 weeks the Standard package and is assessed.

Termination The indication for, and dose of ESA and ASA is prescribed at the discretion of the responsible physician.

Inclusion Criteria:

• Chronic hemodialysis, peritoneal dialysis or CKD 5 treated conservatively
• aged 18-85
• indication for treatment with Erythropoiesis-stimulating agents (ESA)

Exclusion Criteria:

1. Known allergy to ASA
2. Known contraindication to ASA, e.g. recent bleeding episode.
3. Known indication for ASA. If the patient is being treated with ASA, and the physician does not find any indication for this treatment, this can be stopped, and the patient included after 4 weeks.
4. Raised reticulocyte count
5. Current anticoagulant therapy, e.g. warfarin, ADP receptor inhibitor (excepting short-term anticoagulant therapy in connection with dialysis)
6. Short expected length of life
7. Inability to give informed consent
8. Expected non-compliance
9. Active cancer - except for non-melanoma skin-cancer
10. Iron deficiency (defined as a reticulocyte Hgb <1,8 fmol. Patients can be included when their iron deficiency has been cured. .
11. Change in ESA dosis >33,3% within previous 2 month
12. Fertile women. Pregnancy is excessively rare in dialysis patients. Women who are <50 years, or who are still menstruating will be excluded from the study.
13. Stable Aranesp ® dose <20 µg/week.