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PA21, a Novel Phosphate Binder, Improves Renal Osteodystrophy in Rats with Chronic Renal Failure
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modified on 2017-06-22, 19:02 The
effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on
hyperphosphatemia and its accompanying bone abnormality in chronic kidney
disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with
adenine-induced chronic renal failure (CRF) were prepared by feeding them an
adenine-containing diet for four weeks. They were also freely fed a diet that
contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or
lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical
parameters were measured and bone histomorphometry was performed for femurs, which
were isolated after drug treatment. Serum phosphorus and parathyroid hormone
(PTH) levels were higher in the CRF rats. Administration of phosphate binders
for four weeks decreased serum phosphorus and PTH levels in a dose-dependent
manner and there were significant decreases in the AUC0-28 day of
these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate
hydrate groups compared with that in the CRF control group. Moreover, osteoid
volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical
porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2%
lanthanum carbonate hydrate groups. These results suggest that PA21 is
effective against hyperphosphatemia, secondary hyperparathyroidism, and bone
abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate
hydrate are, and that PA21 is a new potential alternative to phosphate binders.
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Keywords
CKD-MBDHyperphosphatemiahyperparathyroidismrenal osteodystrophybone abnormalitiesChronic Renal Failure Ratsserum urea nitrogenserum phosphorus levelsBone histomorphometry analysishyperphosphatemia treatmentPhosphate BindersSucroferric oxyhydroxidelanthanum carbonateSevelamer hydrochlorideMedical Biochemistry: Inorganic Elements and CompoundsBasic PharmacologyMedicinePharmacology