AUTHORS
Annabel Biruete, Corinne E Metzger, Neal X Chen, Elizabeth A Swallow, Curtis Vrabec, Erica L Clinkenbeard, Alexander J Stacy, Shruthi Srinivasan, Kalisha O'Neill, Keith G Avin, Matthew R Allen, Sharon M Moe
ABSTRACT
Background
Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) vs. IV iron on CKD-MBD and iron homeostasis in moderate CKD.
Methods
We tested the effects of 10 weeks of 2% FC vs. IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis, and oxidative stress.
Results
CKD rats had azotemia, elevated phosphorus, PTH, and FGF23. Compared to untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23, and a trend (p = 0.07) towards lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared to NL animals, CKD animals had higher bone turnover, lower trabecular volume, and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased transferrin saturation rate compared to untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD.
Conclusions
Oral FC improved phosphorus homeostasis, some iron-related parameters, and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-to advanced CKD.