TY - JOUR
T1 - Phosphate Balance and CKD–Mineral Bone Disease
AU - Sprague, Stuart M.
AU - Martin, Kevin J.
AU - Coyne, Daniel W.
N1 - Funding Information:
Dr. Sprague reports grants and personal fees from Ardelyx, grants from Amgen, grants and personal fees from Opko Pharm, grants and personal fees from Vifor, grants, and personal fees from Reata, outside of submitted work. Dr. Coyne reports personal fees from FBC-Renal Therapies Group, personal fees from Ardelyx, outside the submitted work. Dr. Martin reports grants from Ardelyx, Inc., other fees from Ardelyx, Inc, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/8
Y1 - 2021/8
N2 - Chronic kidney disease–mineral bone disorder (CKD-MBD) is a common comorbidity in patients with CKD. Characterized by laboratory abnormalities, bone abnormality, and vascular calcification, CKD-MBD encompasses a group of mineral and hormone disturbances that are strongly associated with increased cardiovascular (CV) morbidity and mortality. Abnormal serum phosphate concentrations are an independent risk factor for CV morbidity and mortality, and overall mortality. Phosphate retention plays a central role in initiating and driving many other disturbances in CKD-MBD (e.g., increased parathyroid hormone and fibroblast growth factor 23 concentrations, hypocalcemia, low vitamin D) that are also linked to increased CV risk. Thus, effective phosphate control is a logical therapeutic target for CKD-MBD treatment. Current phosphate management strategies (dietary restrictions, dialysis, phosphate binders) are insufficient to consistently achieve and maintain target phosphate concentrations in patients on dialysis. Phosphate binders reduce available phosphate for intestinal absorption but do not impair the dominant phosphate absorption pathway. Novel therapies that consider new mechanistic understandings of intestinal phosphate absorption are needed. One such therapy is tenapanor, a targeted sodium-hydrogen exchanger isoform 3 inhibitor that has been shown to reduce serum phosphate concentrations in multiple clinical trials. Tenapanor has a novel mechanism of action that reduces intestinal phosphate absorption in the primary paracellular phosphate absorption pathway.
AB - Chronic kidney disease–mineral bone disorder (CKD-MBD) is a common comorbidity in patients with CKD. Characterized by laboratory abnormalities, bone abnormality, and vascular calcification, CKD-MBD encompasses a group of mineral and hormone disturbances that are strongly associated with increased cardiovascular (CV) morbidity and mortality. Abnormal serum phosphate concentrations are an independent risk factor for CV morbidity and mortality, and overall mortality. Phosphate retention plays a central role in initiating and driving many other disturbances in CKD-MBD (e.g., increased parathyroid hormone and fibroblast growth factor 23 concentrations, hypocalcemia, low vitamin D) that are also linked to increased CV risk. Thus, effective phosphate control is a logical therapeutic target for CKD-MBD treatment. Current phosphate management strategies (dietary restrictions, dialysis, phosphate binders) are insufficient to consistently achieve and maintain target phosphate concentrations in patients on dialysis. Phosphate binders reduce available phosphate for intestinal absorption but do not impair the dominant phosphate absorption pathway. Novel therapies that consider new mechanistic understandings of intestinal phosphate absorption are needed. One such therapy is tenapanor, a targeted sodium-hydrogen exchanger isoform 3 inhibitor that has been shown to reduce serum phosphate concentrations in multiple clinical trials. Tenapanor has a novel mechanism of action that reduces intestinal phosphate absorption in the primary paracellular phosphate absorption pathway.
KW - chronic kidney disease mineral bone disorder
KW - fibroblast growth factor 23
KW - hyperphosphatemia
KW - parathyroid hormone
KW - phosphate absorption
KW - vascular calcification
UR - http://www.scopus.com/inward/record.url?scp=85111021907&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2021.05.012
DO - 10.1016/j.ekir.2021.05.012
M3 - Review article
C2 - 34386654
AN - SCOPUS:85111021907
SN - 2468-0249
VL - 6
SP - 2049
EP - 2058
JO - Kidney International Reports
JF - Kidney International Reports
IS - 8
ER -