Quantitative Mass Transfer of SFP-iron From Dialysate to Blood in CKD-HD Patients

• A total of 12 subjects on standard 3X/week hemodialysis will be studied in 2 groups (6 subjects per group)
• 2 primary dialyzer membranes will be studied.:

• Polyamide Membrane (Gambro Polyflux series: 17R and 21R)
• Cellulose Triacetate (Baxter CT series: CT-190)
• Each 1-week treatment cycle will include 3 haemodialysis (HD) sessions per subject, including 2 study treatment-HD sessions and 1 non-treatment-HD session per subject. Treatment-HD sessions will be conducted midweek and end-of-week (i.e. Dialysis days 3 and 5 of each week with a 1 day interdialytic interval) to avoid excessive fluid shifts due to the increased UF needed during the non-treatment HD session (conducted at beginning of the week; HD day 1).
• Within each group, each subject will be randomized to 1 of 6 treatment sequences. The treatments to be investigated are: Control; new dialyzer, reused dialyzer, low blood flow/dialysate flow, Low bicarbonate concentration and a different synthetic dialyzer membrane (PAES)
• Blood for a complete serum iron profile over time will be obtained during the new dialyzer (SFP/standard bicarbonate/new dialyzer/ high Qb and Qd) for all subjects. This will necessitate approximately a 24-hour inpatient confinement to obtain blood at specified time intervals after dialysis is completed. Blood for a partial iron profile will be collected during the dialysis sessions at all other dialysis sessions.
• Each of the 6 enrolled subjects per dialyzer membrane type will be assigned to a different sequence of treatments to help ensure that the treatment sequence does not affect the analysis (Note: the first dialysis sessions of each of the 3 study weeks, i.e. HD1, HD4 and HD7, are non-study related sessions during which no study procedures are performed except for adverse event collection.
• Patients should not be receiving any of the following medications from screening through the end of the study:

• Oral iron preparations, including multivitamin supplements containing iron
• Intravenous iron preparations
• Doses of ESA's should not be changed from screening to the end of the study.

Inclusion criteria

• Adult subject ≥ 18 years of age undergoing chronic hemodialysis for chronic kidney disease (CKD) for at least 3 months, expected to remain on hemodialysis and be able to complete the study.
• Screening Hgb ≥ 9.5 g/dL.
• Screening transferrin saturation % (TSAT) ≥ 15% to ≤ 45%.
• Screening serum ferritin ≥ 200 to ≤ 1200 µg/L.
• Subject's standard dialyzer membrane is one of the 2 types, i.e. Baxter CT-190 or Gambro 17R or 21R.
• The subject uses a reprocessed dialyzer for standard HD treatments.
• Prescribed dialysis 3X/week.
• Minimally adequate measured dialysis dose defined as URR (urea reduction ratio) ≥ 65%, or single-pool Kt/V (dialyzer clearance of urea multiplied by dialysis time, divided by patient's total body water) ≥ 1.2, or KIDt/V (online dialyzer clearance measured using ionic dialysance multiplied by dialysis time, divided by patients total body water) ≥ 1.2.
• Stable dialyzer blood flow rate that is generally ≥ 350 mL/min and acceptable to the Investigator.
• Stable dialysate flow rate that is generally ≥ 600 mL/min and acceptable to the Investigator.
• Vascular access for dialysis that will be used upon enrollment with stable function in the judgment of the Investigator.
• Female subjects must be either amenorrheic for ≥ 1 year or agree to not become pregnant by continuous use of an effective birth control method acceptable to the Investigator for the duration of their participation in the study.
• Must be willing and able to provide written informed consent directly or through their authorized representative.

Exclusion criteria

• Subject has a living kidney donor identified or living-donor kidney transplant scheduled during study participation. (Note: Patients awaiting deceased-donor transplant need not be excluded.)
• Vascular access for hemodialysis is a femoral catheter.
• Known active bleeding from any site other than AV fistula or graft (e.g., gastrointestinal, hemorrhoidal, nasal, pulmonary, etc.).
• Scheduled surgery during the study.
• RBC or whole blood transfusion within 4 weeks prior to Screening.
• Hospitalization in the month prior to Screening (except for vascular access surgery) that, in the opinion of the Investigator, confers a significant risk of hospitalization during the course of this study.
• Evidence of current malignancy involving a site other than skin (except any melanoma, which renders the patient non-eligible).
• History of drug or alcohol abuse within the last 6 months.
• Regularly requiring hemodialysis more than three times per week.
• Noncompliance with dialysis regimen in the opinion of the Investigator.
• Pregnancy or intention to become pregnant before completing all study drug treatment.
• Known ongoing inflammatory disorder (other than CKD), such as systemic lupus erythematosus, rheumatoid arthritis, or other collagen-vascular disease undergoing a disease flare.
• Any current febrile illness (e.g., oral temperature > 100.4°F, 38°C). (The patient may subsequently become eligible at least 1 week after resolution of the illness).
• Known active bacterial, tuberculosis, fungal, viral, or parasitic infection requiring anti-microbial therapy or anticipated to require anti-microbial therapy during the patient's participation in this study.
• Occult tuberculosis requiring prophylactic treatment with anti-tubercular drug(s) that overlaps with the patient's participation in this study.
• Known positive status for hepatitis B surface antigen (hepatitis B testing is not required as part of this protocol).
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this protocol).
• Cirrhosis of the liver based on histological criteria or clinical criteria (i.e., presence of ascites, esophageal varices, multiple spider nevi, or history of hepatic encephalopathy).
• Active hepatitis with ALT and/or AST levels consistently greater than twice the upper limit of normal at any time during the two months prior to enrollment.
• Participation in a study of an investigational drug or device within 30 days prior to randomization in this study.