Please select the eligibility criteria that correspond to the clinical trial below.
Title: Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome
Brief Summary: Erythropoietin (EPO) treatment in patients with the severe cardiorenal syndrome increases cardiac performance and decreases progression of renal failure by dampening the main driving forces of the cardiorenal syndrome in part via non-erythropoietic pathways.

I. Does EPO administration to patients with the severe cardiorenal syndrome increase cardiac performance and decrease progression of renal disease?

II. Does EPO treatment affect the main driving forces of the cardiorenal connection, that is, dampen the activated renin-angiotensin system (RAS), attenuate increased reactive oxygen species (ROS), normalize increased sympathetic activity, and decrease inflammation?

III. Does EPO treatment positively affect the cell function of patients with the cardiorenal syndrome:

1. are gene expression signatures of leukocytes positively influenced by EPO treatment,
2. does EPO shift the Jak/STAT pathway to a less pro-inflammatory profile in monocytes, and
3. are function and number of endothelial progenitor cells (EPCs) affected by treatment with EPO in the cardiorenal syndrome?

IV. Can the direct actions of EPO be differentiated from the effects on hemoglobin levels?


Options:
A: Inclusion Criteria:

1. Written informed consent obtained.
2. Patients age between 18 and 70 years.
3. Patients who are medically stable on hemodialysis for a minimum of 3 months.
4. Patients on Eprex® treatment for CRF related anemia and maintaining Hb level at or above 9 g/dL(90g/L) while on a stable dose (no change in dose) of Epoetin within 6 weeks preceding the screening phase of this study.
5. Patients who have a serum ferritin level greater than 100μg/L and/or transferrin saturation at least 20% within 3 months preceding the screening phase of this study.

Exclusion Criteria:

1. Pregnant or nursing woman, or women of childbearing potential without an effective method of birth control. Effective birth control methods are oral contraception, Norplant, surgical sterilization, IUD or diaphragms in conjunction with spermicidal foam and condom on the male partner.
2. Participation in any drug trial in which the patient received an Epoetin investigational drug within 30 days preceding the screening phase of this study.
3. Those persons directly involved in the conduct of the study.
4. Poorly controlled hypertension with diastolic blood pressures persistently greater than 110 mmHg at baseline observation.
5. History of seizure disorder.
6. Active acute or chronic infection or inflammatory disease.
7. Any illness that had required hospitalization within the last one month.
8. Had blood transfusion within the last three months.
9. Significant hematologic abnormalities (Evidence of hemolysis by laboratory tests, unexplained acquired microcytosis, thrombocytosis (\>500,000/mm3))
10. Severe hyperparathyroidism
11. Diagnosed to have malignant tumor or who have residual tumor after anti-cancer therapy.
B: Inclusion Criteria:

* Patients with moderate renal failure (glomerular filtration rate \[GFR\] by Cockroft formula of 20-70 ml/min)
* Patients with heart failure NYHA class II-III-IV
* Hemoglobin (Hb) between 6.4 - 7.8 mmol/L in men and between 6.0 - 7.4 mmol/L in women
* Age \> 18 years, \< 80 years
* Written informed consent must be obtained from the subject or legally accepted representative before study-specific procedures, including screening procedures, are performed.

Exclusion Criteria:

* Therapy within 1 year before randomisation or any planned erythropoietic therapy between randomisation and study day 1
* Known intolerance to EPO administration
* Previously suspected of or confirmed to have neutralizing antibodies to recombinant human erythropoietin (rHuEPO)
* Uncontrolled hypertension (RR \> 160 systolic, \>100 diastolic)
* Forms of secondary hypertension other than renal hypertension
* Uncontrolled diabetes (HbA1c \> 8.0 %)
* Primary dyslipidemia
* Kidney transplantation
* Proteinuria \> 3.5 g/L
* Acute renal failure or rapidly progressive glomerulonephritis
* Hyperparathyroidism (parathyroid hormone \[PTH\] \> 40)
* Bleeding or haemolysis as a cause of anaemia
* Deficiency of iron, folate, and/or vitamin B12
* Presence of chronic inflammatory disease or clinically significant infection
* Haematologic malignancy or solid tumour \< 5 years ago
* Chronic liver disease
* Haemoglobinopathies
* Alcohol and/or drug abuse
* Enrolment in another study
* Child bearing potential (pre-menopausal woman who is not using adequate contraceptive precautions)
* Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
C: Inclusion Criteria:

* adult patients \>=18 years of age;
* chronic renal anemia;
* on dialysis therapy for at least 12 weeks before screening;
* receiving IV epoetin for at least 8 weeks before screening.

Exclusion Criteria:

* women who are pregnant, breastfeeding or using unreliable birth control methods;
* administration of another investigational drug within 4 weeks before screening, or during the study period.
D: Inclusion Criteria:

* Chronic Kidney Disease:Glomerular filtration rate (GFR) \> 15 mL/min and \> 50 mL/min as calculated by the central lab. HB\<11 g/dL upon study enrollment. The GFR for assessment of patient eligibility will be determined using the formula derived from the Modification of Diet for Renal Disease (MDRD) Study.

Exclusion Criteria:

* Pregnant or lactating women
* Presence of uncontrolled hypertension
* Known hypersensitivity to mammalian cell-derived products or human albumin
* Active gastrointestinal bleeding
* Iron overload defined as a transferrin saturation \>70% or ferritin \>1000 ng/mL
* History of frequent blood transfusions in the past 6 months
* Unstable angina or angina pectoris at rest
* Severe chronic obstructive pulmonary disease requiring routine use of supplemental oxygen
* Severe liver dysfunction that is defined by an international normalized ratio \>2.0, not caused by an anticoagulant
* Severe malnutrition
* Active hematological disease (eg, sickle cell anemia, thalassemia)
* Active malignancy (usually defined as malignancy requiring current chemotherapy or radiotherapy)
* Patients with current seizure disorder or activity
* Patients currently receiving RRT (patient can not be on dialysis or have had a kidney transplant)
* Patients who have received Epoetin Alpha within 6 weeks prior to study entry

Answer: B