Erythropoiesis-stimulating agents (ESAs) have become a hallmark of anaemia 
therapy in patients with chronic kidney disease (CKD). Although different ESAs 
are available for the treatment of renal anaemia, each nephrologist should 
select a single ESA for an individual patient. Epoetin alfa and epoetin beta 
have been used 1-3 times weekly but extended-interval dosing up to every 4 weeks 
is also effective in a substantial majority of CKD patients. However, the 
epoetin dose necessary to achieve or maintain target haemoglobin (Hb) levels 
increases substantially as the dosing interval increases. Subcutaneous 
administration of short-acting ESAs is more effective than the intravenous route 
of administration. Darbepoetin alfa and the continuous erythropoietin receptor 
activator (CERA) have been developed as a treatment for anaemia with extended 
administration intervals (every 2 weeks and every 4 weeks, respectively). Dose 
requirements for these long-acting ESAs are independent of the route of 
administration. Patents of short-acting ESAs have expired, which has opened the 
field for biosimilars. Epoetin biosimilars approved by the European Medicines 
Agency (EMA) or the US Food and Drug Administration (FDA) have been shown to 
have a comparable efficacy and safety profile to their originators. An alarming 
increase in pure red cell aplasia (PRCA) in Thailand with follow-on epoetins 
manufactured in Asia (but also those manufactured in Latin America) indicates 
that stringent country-specific approval and pharmacovigilance protocols for 
ESAs manufactured in non-North American and non-EU European countries are 
urgently needed. Two PRCA cases occurring with subcutaneous HX575 (one certain, 
one likely) indicate that chances of inducing a more immunogenic product are 
unpredictable, even with a biosimilar epoetin approved under the EMA biosimilar 
approval pathway. Phase III clinical trials with peginesatide, a pegylated 
synthetic peptide-based ESA without any homology to erythropoietin raised safety 
concerns in non-dialysis CKD patients but not in dialysis patients.