Effects of phosphate binder therapy on vascular stiffness in early-stage chronic kidney disease.
OBJECTIVE
Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD.


METHODS
We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months.


RESULTS
There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3.


CONCLUSIONS
Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.
Division of Pediatric Nephrology, Southern Illinois University, Springfield, Ill., USA.
Michael E
ME
Seifert
Lisa
L
de las Fuentes
Marcos
M
Rothstein
Dennis J
DJ
Dietzen
Andrew J
AJ
Bierhals
Steven C
SC
Cheng
Will
W
Ross
David
D
Windus
Víctor G
VG
Dávila-Román
Keith A
KA
Hruska
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D048909:Diabetes Complications / Q000175:diagnosis; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006706:Homeostasis; D006801:Humans; D007811:Lanthanum / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000737:chemistry; D010758:Phosphorus; D016226:Phosphorus, Dietary / Q000378:metabolism; D010865:Pilot Projects; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy*; D012307:Risk Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness
D015415:Biomarkers; D010710:Phosphates; D016226:Phosphorus, Dietary; D010758:Phosphorus; C119467:lanthanum carbonate; D007811:Lanthanum