A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease

Intravenous iron is commonly utilized and is likely a mechanism of renal injury in patients
with CKD. This proposal will provide translational data on the role of intravenous iron to
progression of kidney disease in patients with CKD. Comparison of IV iron with oral iron
will allow testing the hypothesis that IVIR will generate an inflammatory response and
albuminuria in the short-term, that will directly lead to a greater rate of fall in GFR, in
the long-term, compared to oral iron. We hypothesize that after administration of one gram
of IV iron over a course of 8 weeks, renal injury as documented by albuminuria (and fall in
GFR) will be increased with IV iron sucrose therapy compared to those randomized to oral
iron therapy. A randomized, parallel group, controlled trial will be performed. GFR will
be measures every 6 months for two years in 200 participants by iothalamate clearances.

Inclusion Criteria:

- Age greater than 18 years

- Calculated GFR by MDRD formula < or = 60ml/min/1.73m2. We will use the MDRD formula
that incorporates serum creatinine, age, race and sex, but not albumin, and blood
urea nitrogen.

- Presence of anemia and iron deficiency. Anemia will be defined as blood hemoglobin
concentration <12g/dL and iron deficiency will be defined using National Kidney
Foundation/Kidney Disease Outcome Quality Initiative (NFK-K/DOQI) Guidelines as serum
ferritin concentration of <100ng/mL or serum transferrin saturation of <25%.

Exclusion Criteria:

- Pregnant or breastfeeding women or women who are planning to become pregnant or those
not using a reliable form of contraception (oral contraceptives, condoms, and
diaphragms will be considered reliable).

- Known hypersensitivity to iron sucrose (Venofer), iothalamate meglumine (Conray 60,
Mallinckrodt) or iodine.

- Anemia that requires RBD transfusion (Hgb <8g/dL) or may potentially need transfusion
(active gastrointestinal bleeding). It would be unsafe to withdraw 150 mL blood over
the study in such anemic patients.

- Presence of acute renal failure defined as an increase in the baseline serum
creatinine concentration of 0.5 mg/dl over 48 hours. This would produce oxidative
stress by itself, may give unreliable rate of decline in renal function and may
confound results.

- History of IVIR use within 1 month of the study (may confound results of the study if
the baseline oxidative stress is increased).

- Evidence of iron overload (serum ferritin >800ng/nl or transferrin saturation >50%)

- Anemia not caused by iron deficiency eg. sickle cell anemia.

- Surgery or systemic or urinary tract infection within 1 month.

- Organ transplant recipient or therapy with immunosuppressive agents. Nasal or
inhaled corticosteroids will be permitted.