Meanwhile, several clinical problems have been reported, including elevated blood pressure [7], pro-anemic effects caused by concomitant drugs, especially angiotensin-converting enzyme inhibitors [8], anti-rHuEPO effects [9], production of anti-EPO antibodies [10,11], hemoglobin cycling caused by intermittent administration of injectable formulations [12], and ESA-refractory anemia [13]. This evidence concerns the gene EPO and anemia (phenotype).