{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:51:16Z","timestamp":1786373476669,"version":"build-2736575974"},"reference-count":138,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>Maintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last half-century of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.<\/jats:p>","DOI":"10.2215\/cjn.11901115","type":"journal-article","created":{"date-parts":[[2016,2,11]],"date-time":"2016-02-11T15:27:21Z","timestamp":1455204441000},"page":"1088-1100","source":"Crossref","is-referenced-by-count":129,"title":["Phosphate Toxicity in CKD: The Killer among Us"],"prefix":"10.2215","volume":"11","author":[{"given":"Cynthia S.","family":"Ritter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Slatopolsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,2,10]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.nutr.25.050304.092642","article-title":"Regulation of phosphorus homeostasis by the type iia na\/phosphate cotransporter","volume":"25","author":"Tenenhouse","year":"2005","journal-title":"Annu Rev Nutr"},{"key":"B2-20230813","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1053\/j.ajkd.2013.03.042","article-title":"Phosphate homeostasis in CKD: Report of a scientific symposium sponsored by the National Kidney Foundation","volume":"62","author":"Block","year":"2013","journal-title":"Am J Kidney Dis"},{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1006\/bbrc.2001.5084","article-title":"FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate","volume":"284","author":"Bowe","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/sdi.12411","article-title":"Pathophysiology of calcium, phosphorus, and magnesium dysregulation in chronic kidney disease","volume":"28","author":"Felsenfeld","year":"2015","journal-title":"Semin Dial"},{"key":"B5-20230813","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1172\/JCI36479","article-title":"Endocrine functions of bone in mineral metabolism regulation","volume":"118","author":"Quarles","year":"2008","journal-title":"J Clin Invest"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1523-1755.2004.00355.x","article-title":"The phosphatonin pathway: New insights in phosphate homeostasis","volume":"65","author":"Schiavi","year":"2004","journal-title":"Kidney Int"},{"key":"B7-20230813","first-page":"4003","article-title":"The parathyroid is a target organ for FGF23 in rats","volume":"117","author":"Ben-Dov","year":"2007","journal-title":"J Clin Invest"},{"key":"B8-20230813","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1677\/JOE-07-0267","article-title":"Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells","volume":"195","author":"Krajisnik","year":"2007","journal-title":"J Endocrinol"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1161\/CIRCULATIONAHA.105.553198","article-title":"Relation between serum phosphate level and cardiovascular event rate in people with coronary disease","volume":"112","author":"Tonelli","year":"2005","journal-title":"Circulation"},{"key":"B10-20230813","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1097\/01.ASN.0000133041.27682.A2","article-title":"Mineral metabolism, mortality, and morbidity in maintenance hemodialysis","volume":"15","author":"Block","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.2215\/CJN.00810110","article-title":"Serum phosphate and mortality in patients with chronic kidney disease","volume":"5","author":"Eddington","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B12-20230813","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0002-9343(60)90225-4","article-title":"The pathologic physiology of chronic Bright\u2019s disease. An exposition of the \u201cintact nephron hypothesis\u201d","volume":"28","author":"Bricker","year":"1960","journal-title":"Am J Med"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1056\/NEJM197205182862009","article-title":"On the pathogenesis of the uremic state. An exposition of the \u201ctrade-off hypothesis\u201d","volume":"286","author":"Bricker","year":"1972","journal-title":"N Engl J Med"},{"key":"B14-20230813","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.2215\/CJN.02640310","article-title":"Fibroblast growth factor 23 and disordered vitamin D metabolism in chronic kidney disease: Updating the \u201ctrade-off\u201d hypothesis","volume":"5","author":"Guti\u00e9rrez","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B15-20230813","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1172\/JCI105877","article-title":"Control of phosphate excretion in uremic man","volume":"47","author":"Slatopolsky","year":"1968","journal-title":"J Clin Invest"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1172\/JCI106517","article-title":"On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog","volume":"50","author":"Slatopolsky","year":"1971","journal-title":"J Clin Invest"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/ki.1972.84","article-title":"On the prevention of secondary hyperparathyroidism in experimental chronic renal disease using \u201cproportional reduction\u201d of dietary phosphorus intake","volume":"2","author":"Slatopolsky","year":"1972","journal-title":"Kidney Int"},{"key":"B18-20230813","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1172\/JCI111365","article-title":"Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency","volume":"73","author":"Portale","year":"1984","journal-title":"J Clin Invest"},{"key":"B19-20230813","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1172\/JCI112666","article-title":"Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure","volume":"78","author":"Lopez-Hilker","year":"1986","journal-title":"J Clin Invest"},{"key":"B20-20230813","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1172\/JCI118701","article-title":"Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro","volume":"97","author":"Slatopolsky","year":"1996","journal-title":"J Clin Invest"},{"key":"B21-20230813","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1002\/jbmr.5650110714","article-title":"Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro","volume":"11","author":"Almaden","year":"1996","journal-title":"J Bone Miner Res"},{"key":"B22-20230813","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/oxfordjournals.ndt.a027665","article-title":"A direct effect in vitro of phosphate on PTH release from bovine parathyroid tissue slices but not from dispersed parathyroid cells","volume":"11","author":"Nielsen","year":"1996","journal-title":"Nephrol Dial Transplant"},{"key":"B23-20230813","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ki.1997.41","article-title":"Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism","volume":"51","author":"Gogusev","year":"1997","journal-title":"Kidney Int"},{"key":"B24-20230813","first-page":"1598","article-title":"Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism","volume":"81","author":"Kifor","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"B25-20230813","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1111\/j.1523-1755.2000.00370.x","article-title":"Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism","volume":"58","author":"Yano","year":"2000","journal-title":"Kidney Int"},{"key":"B26-20230813","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1359\/jbmr.2002.17.12.2206","article-title":"Reversal of secondary hyperparathyroidism by phosphate restriction restores parathyroid calcium-sensing receptor expression and function","volume":"17","author":"Ritter","year":"2002","journal-title":"J Bone Miner Res"},{"key":"B27-20230813","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1046\/j.1523-1755.1999.00386.x","article-title":"Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: Role of dietary phosphate","volume":"55","author":"Brown","year":"1999","journal-title":"Kidney Int"},{"key":"B28-20230813","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1046\/j.1523-1755.2001.00027.x","article-title":"Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor","volume":"60","author":"Ritter","year":"2001","journal-title":"Kidney Int"},{"key":"B29-20230813","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/ki.2012.403","article-title":"Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease","volume":"83","author":"Hill","year":"2013","journal-title":"Kidney Int"},{"key":"B30-20230813","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/ki.2010.313","article-title":"Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease","volume":"78","author":"Hasegawa","year":"2010","journal-title":"Kidney Int"},{"key":"B31-20230813","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1038\/ki.2011.47","article-title":"Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease","volume":"79","author":"Isakova","year":"2011","journal-title":"Kidney Int"},{"key":"B32-20230813","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1093\/ndt\/gfu063","article-title":"Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the elderly","volume":"29","author":"Chudek","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"B33-20230813","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.2215\/CJN.08241109","article-title":"Fibroblast growth factor-23 in early chronic kidney disease: Additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism","volume":"5","author":"Evenepoel","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B34-20230813","doi-asserted-by":"crossref","first-page":"F882","DOI":"10.1152\/ajprenal.00360.2010","article-title":"PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: A bone parathyroid feedback loop","volume":"299","author":"Lavi-Moshayoff","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"B35-20230813","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/ki.2011.107","article-title":"Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo","volume":"80","author":"L\u00f3pez","year":"2011","journal-title":"Kidney Int"},{"key":"B36-20230813","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1038\/ki.2014.215","article-title":"Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription","volume":"86","author":"Meir","year":"2014","journal-title":"Kidney Int"},{"key":"B37-20230813","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/ndt\/gfr384","article-title":"Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism","volume":"27","author":"Koizumi","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"B38-20230813","doi-asserted-by":"crossref","first-page":"F1315","DOI":"10.1152\/ajprenal.00552.2009","article-title":"Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease","volume":"298","author":"Finch","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"B39-20230813","doi-asserted-by":"crossref","first-page":"5358","DOI":"10.1210\/en.2005-0777","article-title":"Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice","volume":"146","author":"Perwad","year":"2005","journal-title":"Endocrinology"},{"key":"B40-20230813","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2215\/CJN.04730510","article-title":"Effects of dietary phosphate and calcium intake on fibroblast growth factor-23","volume":"6","author":"Vervloet","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B41-20230813","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3177\/jnsv.60.140","article-title":"Oral phosphorus supplementation secondarily increases circulating fibroblast growth factor 23 levels at least partially via stimulation of parathyroid hormone secretion","volume":"60","author":"Takasugi","year":"2014","journal-title":"J Nutr Sci Vitaminol (Tokyo)"},{"key":"B42-20230813","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1002\/jbmr.465","article-title":"Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in vitro and accelerates bone formation in vivo","volume":"26","author":"Woo","year":"2011","journal-title":"J Bone Miner Res"},{"key":"B43-20230813","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jsbmb.2012.09.029","article-title":"Extracellular phosphate modulates the effect of 1\u03b1,25-dihydroxy vitamin D3 (1,25D) on osteocyte like cells","volume":"136","author":"Ito","year":"2013","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B44-20230813","doi-asserted-by":"crossref","first-page":"E1101","DOI":"10.1152\/ajpendo.00502.2004","article-title":"Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells","volume":"288","author":"Ito","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B45-20230813","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1677\/JOE-10-0058","article-title":"1alpha,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro","volume":"206","author":"Yamamoto","year":"2010","journal-title":"J Endocrinol"},{"key":"B46-20230813","article-title":"Phosphate enhances Fgf23 expression through reactive oxygen species in UMR-106 cells [published online ahead of print March 21, 2015]","author":"Hori","journal-title":"J Bone Miner Metab"},{"key":"B47-20230813","article-title":"Inflammation and functional iron deficiency regulate fibroblast growth factor 23 production [published online ahead of print November 4, 2015]","author":"David","journal-title":"Kidney Int"},{"key":"B48-20230813","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1159\/000327019","article-title":"Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients","volume":"33","author":"Takeda","year":"2011","journal-title":"Am J Nephrol"},{"key":"B49-20230813","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1210\/en.2013-1627","article-title":"Calcium regulates FGF-23 expression in bone","volume":"154","author":"David","year":"2013","journal-title":"Endocrinology"},{"key":"B50-20230813","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.semnephrol.2012.12.014","article-title":"A systems biology preview of the relationships between mineral and metabolic complications in chronic kidney disease","volume":"33","author":"Quarles","year":"2013","journal-title":"Semin Nephrol"},{"key":"B51-20230813","doi-asserted-by":"crossref","first-page":"F431","DOI":"10.1152\/ajprenal.00199.2012","article-title":"Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone","volume":"303","author":"Krieger","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"B52-20230813","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1210\/jc.2009-1603","article-title":"Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active","volume":"95","author":"Shimada","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B53-20230813","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone Klotho","volume":"309","author":"Kurosu","year":"2005","journal-title":"Science"},{"key":"B54-20230813","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1096\/fj.10-154765","article-title":"Klotho: A novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule","volume":"24","author":"Hu","year":"2010","journal-title":"FASEB J"},{"key":"B55-20230813","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.transproceed.2012.07.150","article-title":"The impact of nephrectomy and renal transplantation on serum levels of soluble Klotho protein","volume":"45","author":"Akimoto","year":"2013","journal-title":"Transplant Proc"},{"key":"B56-20230813","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"Kuro-o","year":"1997","journal-title":"Nature"},{"key":"B57-20230813","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/ki.2015.22","article-title":"Differential expression and regulation of Klotho by paricalcitol in the kidney, parathyroid, and aorta of uremic rats","volume":"87","author":"Ritter","year":"2015","journal-title":"Kidney Int"},{"key":"B58-20230813","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ki.2013.271","article-title":"Early chronic kidney disease-mineral bone disorder stimulates vascular calcification","volume":"85","author":"Fang","year":"2014","journal-title":"Kidney Int"},{"key":"B59-20230813","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1161\/CIRCULATIONAHA.111.053405","article-title":"Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23","volume":"125","author":"Lim","year":"2012","journal-title":"Circulation"},{"key":"B60-20230813","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1136\/heartjnl-2013-304746","article-title":"Reduced Klotho is associated with the presence and severity of coronary artery disease","volume":"100","author":"Navarro-Gonz\u00e1lez","year":"2014","journal-title":"Heart"},{"key":"B61-20230813","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/ki.2012.322","article-title":"Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet","volume":"82","author":"Lau","year":"2012","journal-title":"Kidney Int"},{"key":"B62-20230813","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/ki.2013.3","article-title":"Fibroblast growth factor 23 is not associated with and does not induce arterial calcification","volume":"83","author":"Scialla","year":"2013","journal-title":"Kidney Int"},{"key":"B63-20230813","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/cvr\/cvv187","article-title":"Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue","volume":"108","author":"Mencke","year":"2015","journal-title":"Cardiovasc Res"},{"key":"B64-20230813","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ki.2015.80","article-title":"The vascular secret of Klotho","volume":"87","author":"Lewin","year":"2015","journal-title":"Kidney Int"},{"key":"B65-20230813","doi-asserted-by":"crossref","first-page":"E1308","DOI":"10.1210\/jc.2015-1800","article-title":"-Klotho expression in human tissues","volume":"100","author":"Lim","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B66-20230813","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ki.2010.328","article-title":"Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective","volume":"78","author":"Hu","year":"2010","journal-title":"Kidney Int"},{"key":"B67-20230813","first-page":"7351","article-title":"Klotho: A novel and early biomarker of acute kidney injury after cardiac valve replacement surgery in adults","volume":"8","author":"Liu","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B68-20230813","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3904\/kjim.2015.30.4.489","article-title":"Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury","volume":"30","author":"Seo","year":"2015","journal-title":"Korean J Intern Med"},{"key":"B69-20230813","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/ndt\/gfs460","article-title":"Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: A sequence suggested from a cross-sectional study","volume":"28","author":"Pavik","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"B70-20230813","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev-physiol-030212-183727","article-title":"Fibroblast growth factor 23 and Klotho: Physiology and pathophysiology of an endocrine network of mineral metabolism","volume":"75","author":"Hu","year":"2013","journal-title":"Annu Rev Physiol"},{"key":"B71-20230813","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/ki.2009.464","article-title":"Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease","volume":"77","author":"Galitzer","year":"2010","journal-title":"Kidney Int"},{"key":"B72-20230813","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1681\/ASN.2009121311","article-title":"Klotho deficiency causes vascular calcification in chronic kidney disease","volume":"22","author":"Hu","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B73-20230813","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1006\/bbrc.2000.4226","article-title":"Severely reduced production of klotho in human chronic renal failure kidney","volume":"280","author":"Koh","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"B74-20230813","doi-asserted-by":"crossref","first-page":"e86301","DOI":"10.1371\/journal.pone.0086301","article-title":"Reduced renal \u03b1-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism","volume":"9","author":"Sakan","year":"2014","journal-title":"PLoS One"},{"key":"B75-20230813","doi-asserted-by":"crossref","first-page":"e56695","DOI":"10.1371\/journal.pone.0056695","article-title":"A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease","volume":"8","author":"Kitagawa","year":"2013","journal-title":"PLoS One"},{"key":"B76-20230813","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1053\/j.ajkd.2013.01.024","article-title":"Circulating \u03b1-klotho levels in CKD and relationship to progression","volume":"61","author":"Kim","year":"2013","journal-title":"Am J Kidney Dis"},{"key":"B77-20230813","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/ndt\/gfu291","article-title":"The demonstration of \u03b1Klotho deficiency in human chronic kidney disease with a novel synthetic antibody","volume":"30","author":"Barker","year":"2015","journal-title":"Nephrol Dial Transplant"},{"issue":"Suppl 3","key":"B78-20230813","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1053\/ajkd.1998.v32.pm9820470","article-title":"Clinical epidemiology of cardiovascular disease in chronic renal disease","volume":"32","author":"Foley","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"B79-20230813","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/ckj\/sfu017","article-title":"Cardiovascular risk markers associated with arterial calcification in patients with chronic kidney disease Stages 3 and 4","volume":"7","author":"Kiu Weber","year":"2014","journal-title":"Clin Kidney J"},{"key":"B80-20230813","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1160\/TH09-12-0814","article-title":"Phosphate and vascular calcification: Emerging role of the sodium-dependent phosphate co-transporter PiT-1","volume":"104","author":"Lau","year":"2010","journal-title":"Thromb Haemost"},{"key":"B81-20230813","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1681\/ASN.2009060640","article-title":"Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification","volume":"21","author":"Shroff","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B82-20230813","doi-asserted-by":"crossref","first-page":"e72663","DOI":"10.1371\/journal.pone.0072663","article-title":"Elevated levels of procoagulant plasma microvesicles in dialysis patients","volume":"8","author":"Burton","year":"2013","journal-title":"PLoS One"},{"key":"B83-20230813","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/01.CIR.101.8.841","article-title":"Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes","volume":"101","author":"Mallat","year":"2000","journal-title":"Circulation"},{"key":"B84-20230813","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1093\/ndt\/gfp066","article-title":"The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease","volume":"24","author":"Dursun","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B85-20230813","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1681\/ASN.2014070642","article-title":"Hyperphosphatemia, phosphoprotein phosphatases, and microparticle release in vascular endothelial cells","volume":"26","author":"Abbasian","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B86-20230813","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1681\/ASN.2008040349","article-title":"Association of serum phosphate with vascular and valvular calcification in moderate CKD","volume":"20","author":"Adeney","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B87-20230813","doi-asserted-by":"crossref","first-page":"e36883","DOI":"10.1371\/journal.pone.0036883","article-title":"Phosphorus is associated with coronary artery disease in patients with preserved renal function","volume":"7","author":"Cancela","year":"2012","journal-title":"PLoS One"},{"key":"B88-20230813","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12882-015-0103-8","article-title":"Hyperphosphatemia as an independent risk factor for coronary artery calcification progression in peritoneal dialysis patients","volume":"16","author":"Shang","year":"2015","journal-title":"BMC Nephrol"},{"key":"B89-20230813","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/ki.2013.213","article-title":"Phosphate restriction significantly reduces mortality in uremic rats with established vascular calcification","volume":"84","author":"Finch","year":"2013","journal-title":"Kidney Int"},{"key":"B90-20230813","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1681\/ASN.2006121385","article-title":"Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice","volume":"18","author":"Stubbs","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B91-20230813","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1093\/ndt\/gfu324","article-title":"Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: A fibroblast growth factor 23 mutation identified by exome sequencing","volume":"29","author":"Shah","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"B92-20230813","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1681\/ASN.2010121224","article-title":"FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis","volume":"22","author":"Kendrick","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B93-20230813","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1001\/jama.2011.826","article-title":"Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease","volume":"305","author":"Isakova","year":"2011","journal-title":"JAMA"},{"key":"B94-20230813","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/j.1365-2265.2007.03074.x","article-title":"Relation between plasma fibroblast growth factor-23, serum fetuin-A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function","volume":"68","author":"Roos","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B95-20230813","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1471-2369-14-22","article-title":"Fibroblast growth factor 23 is associated with carotid artery calcification in chronic kidney disease patients not undergoing dialysis: A cross-sectional study","volume":"14","author":"Nakayama","year":"2013","journal-title":"BMC Nephrol"},{"key":"B96-20230813","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/ndt\/gfn571","article-title":"Peripheral vascular calcification in long-haemodialysis patients: Associated factors and survival consequences","volume":"24","author":"Jean","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B98-20230813","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1161\/CIRCULATIONAHA.108.844506","article-title":"Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease","volume":"119","author":"Guti\u00e9rrez","year":"2009","journal-title":"Circulation"},{"key":"B99-20230813","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest"},{"key":"B100-20230813","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.2215\/CJN.04430415","article-title":"Mineral (mal)adaptation to kidney disease--Young Investigator Award Address: American Society of Nephrology Kidney Week 2014","volume":"10","author":"Wolf","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B101-20230813","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bbrc.2010.11.045","article-title":"Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke","volume":"403","author":"Majumdar","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B102-20230813","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1159\/000381937","article-title":"Serum soluble klotho level is associated with abdominal aortic calcification in patients on maintenance hemodialysis","volume":"40","author":"Cai","year":"2015","journal-title":"Blood Purif"},{"key":"B103-20230813","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1681\/ASN.2014050465","article-title":"Klotho and phosphate are modulators of pathologic uremic cardiac remodeling","volume":"26","author":"Hu","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B104-20230813","first-page":"191","article-title":"Medial artery calcification of uremic patients: A histological, histochemical and ultrastructural study","volume":"26","author":"Ballanti","year":"2011","journal-title":"Histol Histopathol"},{"key":"B105-20230813","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1172\/JCI24140","article-title":"Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals","volume":"115","author":"Shao","year":"2005","journal-title":"J Clin Invest"},{"key":"B106-20230813","doi-asserted-by":"crossref","first-page":"440","DOI":"10.2215\/CJN.05130610","article-title":"Prevention and control of phosphate retention\/hyperphosphatemia in CKD-MBD: What is normal, when to start, and how to treat?","volume":"6","author":"Martin","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B107-20230813","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1172\/JCI108781","article-title":"Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog","volume":"60","author":"Rutherford","year":"1977","journal-title":"J Clin Invest"},{"key":"B108-20230813","first-page":"89","article-title":"Organic and inorganic dietary phosphorus and its management in chronic kidney disease","volume":"4","author":"Noori","year":"2010","journal-title":"Iran J Kidney Dis"},{"key":"B109-20230813","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/kisup.2013.96","article-title":"Hyperphosphatemia is a combined function of high serum PTH and high dietary protein intake in dialysis patients","volume":"3","author":"Streja","year":"2013","journal-title":"Kidney Int Suppl (2011)"},{"key":"B110-20230813","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2215\/CJN.05040610","article-title":"Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease","volume":"6","author":"Moe","year":"2011","journal-title":"Clin J Am Soc Nephrol"},{"key":"B112-20230813","first-page":"109","article-title":"Nutritional problems in adult patients with stage 5 chronic kidney disease on dialysis (both haemodialysis and peritoneal dialysis)","volume":"3","author":"Heng","year":"2010","journal-title":"NDT Plus"},{"key":"B113-20230813","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.semnephrol.2008.10.008","article-title":"Assessment of body protein: Energy status in chronic kidney disease","volume":"29","author":"Cano","year":"2009","journal-title":"Semin Nephrol"},{"key":"B114-20230813","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3945\/ajcn.2008.26665","article-title":"Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease?","volume":"88","author":"Shinaberger","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"B115-20230813","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/ndt\/gfq419","article-title":"Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease","volume":"26","author":"Isakova","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"B116-20230813","article-title":"Relationship of dietary phosphate intake with risk of end-stage renal disease and mortality in chronic kidney disease stages 3-5: The Modification of Diet in Renal Disease Study [published online ahead of print September 30, 2015]","author":"Selamet","journal-title":"Kidney Int"},{"key":"B118-20230813","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1056\/NEJMra0912522","article-title":"Oral phosphate binders in patients with kidney failure","volume":"362","author":"Tonelli","year":"2010","journal-title":"N Engl J Med"},{"key":"B119-20230813","doi-asserted-by":"crossref","first-page":"286","DOI":"10.2215\/CJN.05420709","article-title":"Early control of PTH and FGF23 in normophosphatemic CKD patients: A new target in CKD-MBD therapy?","volume":"5","author":"Oliveira","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B120-20230813","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/MNH.0b013e32836214d4","article-title":"Use of phosphate binders in chronic kidney disease","volume":"22","author":"Ketteler","year":"2013","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B121-20230813","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1681\/ASN.2011121213","article-title":"Npt2b deletion attenuates hyperphosphatemia associated with CKD","volume":"23","author":"Schiavi","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B122-20230813","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1681\/ASN.2012030223","article-title":"Effects of phosphate binders in moderate CKD","volume":"23","author":"Block","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B123-20230813","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1681\/ASN.2015020117","article-title":"Rationale and approaches to phosphate and fibroblast growth factor 23 reduction in CKD","volume":"26","author":"Isakova","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B124-20230813","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.2215\/CJN.04211007","article-title":"A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients","volume":"3","author":"Cheng","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"B125-20230813","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1681\/ASN.2009050559","article-title":"Intestinal npt2b plays a major role in phosphate absorption and homeostasis","volume":"20","author":"Sabbagh","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B126-20230813","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1681\/ASN.2013060569","article-title":"Hepatectomy-related hypophosphatemia: A novel phosphaturic factor in the liver-kidney axis","volume":"25","author":"Nomura","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B127-20230813","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.3382\/ps\/pev085","article-title":"Oral peptide specific egg antibody to intestinal sodium-dependent phosphate co-transporter-2b is effective at altering phosphate transport in vitro and in vivo","volume":"94","author":"Bobeck","year":"2015","journal-title":"Poult Sci"},{"key":"B128-20230813","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1172\/JCI61405","article-title":"FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality","volume":"122","author":"Shalhoub","year":"2012","journal-title":"J Clin Invest"},{"key":"B129-20230813","doi-asserted-by":"crossref","first-page":"110","DOI":"10.2215\/CJN.03630509","article-title":"Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD","volume":"5","author":"Wetmore","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B130-20230813","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1056\/NEJMoa1205624","article-title":"Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis","volume":"367","author":"Chertow","year":"2012","journal-title":"N Engl J Med"},{"key":"B131-20230813","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1172\/JCI64184","article-title":"Fibroblast growth factor 23: Friend or foe in uremia?","volume":"122","author":"Moe","year":"2012","journal-title":"J Clin Invest"},{"key":"B132-20230813","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/ndt\/gfi165","article-title":"Klotho reduces apoptosis in experimental ischaemic acute renal failure","volume":"20","author":"Sugiura","year":"2005","journal-title":"Nephrol Dial Transplant"},{"key":"B133-20230813","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/ncomms2240","article-title":"Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart","volume":"3","author":"Xie","year":"2012","journal-title":"Nat Commun"},{"key":"B134-20230813","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1681\/ASN.2014040325","article-title":"Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate","volume":"26","author":"Xie","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B135-20230813","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejphar.2012.09.032","article-title":"The secreted Klotho protein restores phosphate retention and suppresses accelerated aging in Klotho mutant mice","volume":"698","author":"Chen","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"B136-20230813","article-title":"Xeno-Klotho inhibits parathyroid hormone signaling [published online ahead of print August 19, 2015]","author":"Takenaka","journal-title":"J Bone Miner Res"},{"key":"B137-20230813","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1056\/NEJMoa031633","article-title":"Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis","volume":"350","author":"Block","year":"2004","journal-title":"N Engl J Med"},{"key":"B138-20230813","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1681\/ASN.2004060512","article-title":"Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: A randomized, double-blind, multicenter study","volume":"16","author":"Lindberg","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B139-20230813","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1053\/j.ajkd.2008.09.021","article-title":"A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis","volume":"53","author":"Chonchol","year":"2009","journal-title":"Am J Kidney Dis"},{"key":"B140-20230813","doi-asserted-by":"crossref","first-page":"864012","DOI":"10.1155\/2013\/864012","article-title":"Which vitamin D in CKD-MBD? The time of burning questions","volume":"2013","author":"Galassi","year":"2013","journal-title":"BioMed Res Int"},{"key":"B141-20230813","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/ckj\/sfu135","article-title":"The beneficial impact of vitamin D treatment in CKD patients: What\u2019s next?","volume":"8","author":"Morrone","year":"2015","journal-title":"Clin Kidney J"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201606000-00021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:46:10Z","timestamp":1786369570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201606000-00021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,10]]},"references-count":138,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.11901115","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,10]]}}}