A Study of Ferric Citrate to Improve Inflammation and Lipid Levels

In patients with end stage renal disease (ESRD) receiving dialysis, the risk of
cardiovascular death has been estimated to be 10-100 times higher than the general
population without renal disease. This is due in part to high levels of inflammation and
vascular calcification (large deposits of calcium in arteries) found in these patients.
Chronic inflammation is particularly common in patients with ESRD. Parenteral iron therapy,
which is common in patients on dialysis, may contribute to this inflammation and also a
higher cardiovascular risk. Phosphate binders, particularly non-calcium based phosphate
binders, may decrease cardiovascular risk by decreasing inflammation and vascular
calcification. In a study of 10,044 hemodialysis patients, treatment with a phosphate binder
was associated with improved survival. Ferric citrate a non-calcium based phosphate binder
with approximately 210 mg of ferric iron has recently been approved for patients on
hemodialysis. It has been shown to improve serum phosphorus levels and decrease intravenous
iron requirements for patients on hemodialysis. The effect of this phosphate binder on
inflammation and lipid levels is unknown but investigators hypothesize that ferric citrate
has the potential to improve inflammation and lipid levels in patients on hemodialysis by
decreasing intravenous iron requirements and by improving lipid metabolism.

Ferric citrate has the potential to decrease cardiovascular risk through multiple
mechanisms:

1. acting as a non-calcium based binder to decrease serum phosphorus levels and vascular
calcification,

2. decreasing intravenous iron requirements which in turn may decrease inflammation,

3. binding endotoxin (a harmful substance produced by microorganisms) in the gut and

4. improving lipid metabolism.

The purpose of this study is to examine the effect of ferric citrate on inflammatory markers
and lipid levels.

Inclusion Criteria:

- Hemodialysis treatment for ≥ 6 months

- Phosphate binder treatment for ≥ to 1 month

- Maintenance iron therapy with no more than 125mg IV iron weekly≥ to 1 month

- Serum phosphorus levels between 2.5 and 8 at screening

- Serum phosphorus ≥ to 6.0 mg/dL after a 2 week washout period.

- Serum ferritin ≥ 200 and < 600ng/ml after a 2 week washout period

- Serum calcium levels within normal range

- Predicted survival greater than 6 months

Exclusion Criteria:

- Intact PTH< 70 pg/ml or > 1,000 pg/ml

- Oral iron use

- Vitamin C supplement use

- Parathyroidectomy

- Active malignancy

- Hemodialysis via an intravenous catheter or arteriovenous (AV) graft

- Received > 250mg of IV iron over the two weeks prior to screening

- Whole blood transfusion within 3 months prior to screening

- Active bleeding other than from the dialysis access

- Hospitalization within one month prior to screening

- current infection

- Ongoing or uncontrolled inflammatory disorder

- Liver cirrhosis

- Likelihood of imminent renal transplantation