Research Article: PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure

Date Published: July 13, 2017

Publisher: Public Library of Science

Author(s): Atsushi Yaguchi, Satoshi Tatemichi, Hiroo Takeda, Mamoru Kobayashi, Mario Cozzolino.


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.

Partial Text

A decline in kidney function due to chronic kidney disease (CKD) causes mineral disorders. It leads to systemic abnormalities such as vascular calcification and affects prognosis. All pathologies associated with CKD were unified and the concept of CKD-mineral and bone disorder (CKD-MBD) was suggested [1].

PA21, a new phosphate binder, suppressed osteoid formation, fibrosis, and porousness; decreased serum phosphorus and PTH levels; and significantly suppressed OV and Fb.V of trabecular bones and Ct.Po of cortical bones. Thus, PA21 inhibited the progression of ROD by decreasing serum phosphorus levels.