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Background: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested., Methods: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

Accumulation and proliferation of vascular smooth muscle cells are associated with atherosclerosis and hypertension. Proliferation of smooth muscle cells constitutes a major pathological event responsible for long-term failure of coronary and peripheral arterial bypass graft as well as the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The incidence of restenosis after PTCA has been reported to be as high as 40-45% within 3-6 months. Major advantages in recombinant deoxyribonucleic acid (DNA) technology and eukaryotic gene regulation allow to hypothesize gene therapy as a potential treatment for inherited and acquired diseases. Gene therapy is the introduction of genes into somatic cells to correct an inherited or acquired disorder through the synthesis of missing or defective protein. Although no disease has yet been treated by gene therapy, several gene transfer protocols have recently been undertaken. We have studied the expression of foreign DNA that has been introduced into smooth muscle cells after balloon carotid injury in a rat model of angioplasty. The effects of different degree of balloon injury on neointima formation and c-fos expression was also assessed. Our data demonstrate that site-specific gene expression can be achieved by direct gene transfer in vivo and could be applied to the treatment of restenosis after PTCA.