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REVIEW

Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor

, , , &
Pages 151-161 | Received 21 Jan 2024, Accepted 14 May 2024, Published online: 28 May 2024

References

  • Moe S, Drüeke T, Cunningham J, et al.; Kidney Disease: Improving Global Outcomes (KDIGO). Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: improving Global Outcomes (KDIGO). Kidney Int. 2006;69(11):1945–1953. doi:10.1038/sj.ki.5000414
  • Bellasi A, Mandreoli M, Baldrati L, et al. Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction. Clin J Am Soc Nephrol. 2011;6:883–891. doi:10.2215/CJN.07810910
  • Pavik I, Jaeger P, Ebner L, et al. Secreted Klotho and fgf23 in chronic kidney disease stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant. 2013;28:352–359. doi:10.1093/ndt/gfs460
  • Bellasi A, Mangano M, Galassi A, Cozzolino M. CKD-MBD cardiovascular involvement and prognosis. Giorn Ital Nefr. 2017;34(Suppl 69):150–161.
  • Faul C, Amaral AP, Oskouei B, et al. Fgf23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393–4408.
  • Adragao T, Pires A, Lucas C, et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant. 2004;19(6):1480–1488. doi:10.1093/ndt/gfh217
  • Górriz JL, Molina P, Cerverón MJ, et al. Vascular calcification in patients with nondialysis CKD over 3 years. Clin J Am Soc Nephrol. 2015;10(4):654–666. doi:10.2215/CJN.07450714
  • Zhou L, Fu P. The interpretation of KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Chin J Evidence Based Med. 2017;17(8):869–875.
  • Thongprayoon C, Cheungpasitporn W, Mao MA, Sakhuja A, Erickson SB. Admission hyperphosphatemia increases the risk of acute kidney injury in hospitalized patients. J Nephrol. 2018;31(2):241–247. doi:10.1007/s40620-017-0442-6
  • Leaf DE, Wolf M. A physiologic-based approach to the evaluation of a patient with hyperphosphatemia. Am J Kidney Dis. 2013;61(2):330–336. doi:10.1053/j.ajkd.2012.06.026
  • Zheng WH, Yao Y, Zhou H, Xu Y, Huang HB. Hyperphosphatemia and outcomes in critically ill patients: a systematic review and meta-analysis. Front Med. 2022;9:1–11. doi:10.3389/fmed.2022.870637
  • Cernaro V, Santoro D, Lucisano S, Nicocia G, Lacquaniti A, Buemi M. The future of phosphate binders: a perspective on novel therapeutics. Expert Opin Investig Drugs. 2014;23(11):1459–1463. doi:10.1517/13543784.2014.962652
  • Prasad A, Verghese D, Vijaya Rangan S, Sunadarajan N. Spontaneous tumour lysis secondary to gastric adenocarcinoma. BMJ Case Rep. 2024;17(1):e258369. doi:10.1136/bcr-2023-258369
  • Molinaris V, Bianchetti MG, Milani GP, et al. Interferences in the measurement of circulating phosphate: a literature review. Clin Chem Lab Med. 2020;58(12):1971–1977. doi:10.1515/cclm-2020-0281
  • Ogata H, Sugawara H, Yamamoto M, Ito H. Phosphate and coronary artery disease in patients with chronic kidney disease. J Atheroscler Thromb. 2024;31(1):1–14. doi:10.5551/jat.RV22012
  • Vervloet M, Cozzolino M. Vascular calcification in chronic kidney disease: different bricks in the wall? Kidney Int. 2017;91(4):808–817. doi:10.1016/j.kint.2016.09.024
  • Cozzolino M, Gallieni M, Brancaccio D. Vascular calcification in uremic conditions: new insights into pathogenesis. Semin Nephrol. 2006;26(1):33–37. doi:10.1016/j.semnephrol.2005.06.008
  • Nikolajević J, Šabovič M. Inflammatory, metabolic, and coagulation effects on medial arterial calcification in patients with peripheral arterial disease. Int J Mol Sci. 2023;24(4):3132. doi:10.3390/ijms24043132
  • Ishimura E, Taniwaki H, Tabata T, et al. Cross-sectional association of serum phosphate with carotid intima-medial thickness in hemodialysis patients. Am J Kidney Dis. 2005;45(5):859–865. doi:10.1053/j.ajkd.2005.02.008
  • Jung J, Jeon-Slaughter H, Nguyen H, et al. Hyperphosphatemia and its relationship with blood pressure, vasoconstriction, and endothelial cell dysfunction in hypertensive hemodialysis patients. BMC Nephrol. 2022;23(1):291. doi:10.1186/s12882-022-02918-0
  • Okute Y, Shoji T, Shimomura N, et al. Serum phosphate as an independent factor associated with cholesterol metabolism in patients undergoing hemodialysis: a cross-sectional analysis of the DREAM cohort. Nephrol Dial Transplant. 2023;38(4):1002–1008. doi:10.1093/ndt/gfac222
  • Massy ZA, Merkling T, Wagner S, et al. Association of serum phosphate with efficacy of statin therapy in hemodialysis patients. Clin J Am Soc Nephrol. 2022;17(4):546–554. doi:10.2215/CJN.12620921
  • Eddington H, Hoefield R, Sinha S, et al. Serum phosphate and mortality in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010;5(12):2251–2257. doi:10.2215/CJN.00810110
  • Molina P, Molina MD, Pallardó LM, et al. Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study. J Nephrol. 2021;34(4):1189–1199. doi:10.1007/s40620-020-00916-9
  • Zhou W, Zhang M, Ni Z. Acute phosphate nephropathy leading to graft failure. Clin Exp Nephrol. 2019;23(1):144–145. doi:10.1007/s10157-018-1608-9
  • Al Harbi SA, Al-Dorzi HM, Al Meshari AM, et al. Association between phosphate disturbances and mortality among critically ill patients with sepsis or septic shock. BMC Pharmacol Toxicol. 2021;22(1):30. doi:10.1186/s40360-021-00487-w
  • Black LP, Mohseni M, Shirazi E, et al. Association of early serum phosphate levels and mortality in patients with sepsis. West J Emerg Med. 2023;24(3):416–423. doi:10.5811/WESTJEM.58959
  • Liu Z, Li T, Du Y, Li C, Chong W. Both hypophosphatemia and hyperphosphatemia are associated with increased mortality in septic patients. Front Nephrol. 2022;2:1–16. doi:10.3389/fneph.2022.935288
  • Yamada S, Tsuruya K, Taniguchi M, et al. Association between serum phosphate levels and stroke risk in patients undergoing hemodialysis: the Q-cohort study. Stroke. 2016;47(9):2189–2196. doi:10.1161/STROKEAHA.116.013195
  • Li T, Xie Y, Bowe B, Xian H, Al-Aly Z. Serum phosphorus levels and risk of incident dementia. PLoS One. 2017;12(2):e0171377.
  • Otobe Y, Hiraki K, Izawa KP, Sakurada T, Shibagaki Y. Relationship between serum inorganic phosphorus levels and cognitive decline over 2 years in older adults with pre-dialysis chronic kidney disease. Clin Exp Nephrol. 2020;24(3):286–287. doi:10.1007/s10157-019-01819-1
  • Beto J, Bhatt N, Gerbeling T, Patel C, Drayer D. Overview of the 2017 KDIGO CKD-MBD Update: practice Implications for Adult Hemodialysis Patients. J Ren Nutr. 2019;29(1):2–15. doi:10.1053/j.jrn.2018.05.006
  • D’Alessandro C, Piccoli GB, Cupisti A. The ”phosphorus pyramid”: a visual tool for dietary phosphate management in dialysis and CKD patients. BMC Nephrol. 2015;16(1):9. doi:10.1186/1471-2369-16-9
  • Hutchison AJ. Oral phosphate binders. Kidney Int. 2009;75(9):906–914. doi:10.1038/ki.2009.60
  • Cernaro V, Longhitano E, Calabrese V, et al. Progress in pharmacotherapy for the treatment of hyperphosphatemia in renal failure. Expert Opin Pharmacother. 2023;24(15):1737–1746. doi:10.1080/14656566.2023.2243817
  • Tsuchiya K, Akihisa T. The Importance of Phosphate Control in Chronic Kidney Disease. Nutrients. 2021;13(5):1670. doi:10.3390/nu13051670
  • Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2017;7(1):1–59.
  • Block GA, Wheeler DC, Persky MS, et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol. 2012;23(8):1407–1415. doi:10.1681/ASN.2012030223
  • Ogata H, Takeshima A, Ito H. An update on phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a review of safety profiles. Expert Opin Drug Saf. 2022;21(7):947–955. doi:10.1080/14740338.2022.2044472
  • Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: a review of toxic actions and effects. Interdiscip Toxicol. 2019;12(2):45–70.
  • Cernaro V, Santoro D, Lacquaniti A, et al. Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide. Int J Nephrol Renovasc Dis. 2016;9:11–19. doi:10.2147/IJNRD.S78040
  • Xu JP, Zeng RX, Liao PD, Zhang MZ. Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: a meta-analysis of randomized controlled trials. Hemodial Int. 2022;26(2):223–233. doi:10.1111/hdi.12988
  • Ogata H, Fukagawa M, Hirakata H, et al. Effect of treating hyperphosphatemia with lanthanum carbonate vs calcium carbonate on cardiovascular events in patients with chronic kidney disease undergoing hemodialysis: the LANDMARK randomized clinical trial. JAMA. 2021;325(19):1946–1954.
  • Ogata H, Fukagawa M, Hirakata H, Kagimura T, Akizawa T; LANDMARK Investigators and Committees. Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial. Clin Exp Nephrol. 2022;26(12):1223–1232. doi:10.1007/s10157-022-02270-5
  • Ruospo M, Palmer SC, Natale P, et al. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2018;8(8):CD006023. doi:10.1002/14651858.CD006023.pub3
  • Di Iorio B, Bellasi A, Russo D; INDEPENDENT Study Investigators. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol. 2012;7(3):487–493. doi:10.2215/CJN.03820411
  • Molina P, Molina MD, Carrero JJ, et al. Sevelamer use and mortality in people with chronic kidney disease stages 4 and 5 not on dialysis. J Clin Med. 2023;12(24):7631. doi:10.3390/jcm12247631
  • Basutkar RS, Varghese R, Mathew NK, Sankar Indira P, Viswanathan B, Sivasankaran P. Systematic review and meta-analysis of potential pleiotropic effects of sevelamer in chronic kidney disease: beyond phosphate control. Nephrology. 2022;27(4):337–354.
  • Vervloet MG, van Ballegooijen AJ. Prevention and treatment of hyperphosphatemia in chronic kidney disease. Kidney Int. 2018;93(5):1060–1072. doi:10.1016/j.kint.2017.11.036
  • Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1–S107. Erratum in: Am J Kidney Dis. 2021;77(2):308.
  • Lee D-Y, Han SY, Lee K, et al. Association of a low protein diet with depressive symptoms and poor health-related quality of life in CKD. J Psychiatr Res. 2023;161:282–288. doi:10.1016/j.jpsychires.2023.02.032
  • Brown-Tortorici AR, Narasaki Y, You AS, et al. The interplay between dietary phosphorous, protein intake, and mortality in a prospective hemodialysis cohort. Nutrients. 2022;14(15):3070. doi:10.3390/nu14153070
  • Li J, Wang L, Han M, et al. The role of phosphate-containing medications and low dietary phosphorus-protein ratio in reducing intestinal phosphorus load in patients with chronic kidney disease. Nutr Diabetes. 2019;9(1):14. doi:10.1038/s41387-019-0080-2
  • Calvo MS, Moshfegh AJ, Tucker KL. Assessing the health impact of phosphorus in the food supply: issues and considerations. Adv Nutr. 2014;5(1):104–113. doi:10.3945/an.113.004861
  • Zhang W, Du Q, Xiao J, et al. Modification and validation of the phosphate removal model: a multicenter study. Kidney Blood Press Res. 2021;46(1):53–62. doi:10.1159/000511375
  • Cernaro V, Calderone M, Gembillo G, et al. Phosphate control in peritoneal dialysis patients: issues, solutions, and open questions. Nutrients. 2023;15(14):3161. doi:10.3390/nu15143161
  • Guedes M, Bieber B, Dasgupta I, et al. Serum phosphorus level rises in US hemodialysis patients over the past decade: a DOPPS special report. Kidney Med. 2022;5(2):100584. doi:10.1016/j.xkme.2022.100584
  • Cozzolino M, Ketteler M, Wagner CA. An expert update on novel therapeutic targets for hyperphosphatemia in chronic kidney disease: preclinical and clinical innovations. Expert Opin Ther Targets. 2020;24(5):477–488. doi:10.1080/14728222.2020.1743680
  • Kalantar-Zadeh K, Forfang D, Bakris G, Martin KJ, Moe SM, Sprague SM. Managing phosphate burden in patients receiving dialysis: beyond phosphate binders and diet. Kidney360. 2023;4(11):1650–1656. doi:10.34067/KID.0000000000000262
  • Kovesdy CP, Adebiyi A, Rosenbaum D, Jacobs JW, Quarles LD. Novel treatments from inhibition of the intestinal sodium-hydrogen exchanger 3. Int J Nephrol Renovasc Dis. 2021;14:411–420. doi:10.2147/IJNRD.S334024
  • Maruyama S, Marbury TC, Connaire J, Ries D, Maxwell W, Rambaran C. NaPi-IIb inhibition for hyperphosphatemia in CKD hemodialysis patients. Kidney Int Rep. 2020;6(3):675–684. doi:10.1016/j.ekir.2020.12.017
  • Larsson TE, Kameoka C, Nakajo I, et al. NPT-IIb inhibition does not improve hyperphosphatemia in CKD. Kidney Int Rep. 2017;3(1):73–80. doi:10.1016/j.ekir.2017.08.003
  • Katai K, Tanaka H, Tatsumi S, et al. Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine. Nephrol Dial Transplant. 1999;14(5):1195–1201. doi:10.1093/ndt/14.5.1195
  • Eto N, Miyata Y, Ohno H, Yamashita T. Nicotinamide prevents the development of hyperphosphataemia by suppressing intestinal sodium-dependent phosphate transporter in rats with adenine-induced renal failure. Nephrol Dial Transplant. 2005;20(7):1378–1384. doi:10.1093/ndt/gfh781
  • Ginsberg C, Ix JH. Nicotinamide and phosphate homeostasis in chronic kidney disease. Curr Opin Nephrol Hypertens. 2016;25(4):285–291. doi:10.1097/MNH.0000000000000236
  • Lenglet A, Liabeuf S, El Esper N, et al. Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study. Nephrol Dial Transplant. 2017;32(5):870–879. doi:10.1093/ndt/gfx249
  • Malhotra R, Katz R, Hoofnagle A, et al. The effect of extended release niacin on markers of mineral metabolism in CKD. Clin J Am Soc Nephrol. 2018;13(1):36–44. doi:10.2215/CJN.05440517
  • Hill Gallant KM, Stremke ER, Trevino LL, et al. EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients. Kidney Int. 2021;99(5):1225–1233. doi:10.1016/j.kint.2020.09.035
  • Hill Gallant KM, Vorland CJ. Intestinal phosphorus absorption: recent findings in translational and clinical research. Curr Opin Nephrol Hypertens. 2021;30(4):404–410. doi:10.1097/MNH.0000000000000719
  • King AJ, Siegel M, He Y, et al. Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. Sci Transl Med. 2018;10(456):eaam6474. doi:10.1126/scitranslmed.aam6474
  • Johansson S, Rosenbaum DP, Knutsson M, Leonsson-Zachrisson M. A phase 1 study of the safety, tolerability, pharmacodynamics, and pharmacokinetics of tenapanor in healthy Japanese volunteers. Clin Exp Nephrol. 2017;21(3):407–416. doi:10.1007/s10157-016-1302-8
  • Johansson S, Rosenbaum DP, Palm J, et al. Tenapanor administration and the activity of the H+ -coupled transporter PepT1 in healthy volunteers. Br J Clin Pharmacol. 2017;83(9):2008–2014. doi:10.1111/bcp.13313
  • Johansson S, Leonsson-Zachrisson M, Knutsson M, et al. Preclinical and healthy volunteer studies of potential drug-drug interactions between tenapanor and phosphate binders. Clin Pharmacol Drug Dev. 2017;6(5):448–456. doi:10.1002/cpdd.307
  • Johansson S, Rosenbaum DP, Ahlqvist M, et al. Effects of tenapanor on cytochrome P450-mediated drug-drug interactions. Clin Pharmacol Drug Dev. 2017;6(5):466–475. doi:10.1002/cpdd.346
  • Block GA, Rosenbaum DP, Leonsson-Zachrisson M, et al. Effect of tenapanor on serum phosphate in patients receiving hemodialysis. J Am Soc Nephrol. 2017;28(6):1933–1942. doi:10.1681/ASN.2016080855
  • Block GA, Rosenbaum DP, Yan A, Greasley PJ, Chertow GM, Wolf M. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia. Nephrol Dial Transplant. 2019;34(2):339–346. doi:10.1093/ndt/gfy061
  • Inaba M, Une Y, Ikejiri K, Kanda H, Fukagawa M, Akizawa T. Dose-response of tenapanor in patients with hyperphosphatemia undergoing hemodialysis in Japan-A Phase 2 randomized trial. Kidney Int Rep. 2021;7(2):177–188. doi:10.1016/j.ekir.2021.11.008
  • Block GA, Rosenbaum DP, Yan A, Chertow GM. Efficacy and safety of tenapanor in patients with hyperphosphatemia receiving maintenance hemodialysis: a randomized Phase 3 trial. J Am Soc Nephrol. 2019;30(4):641–652. doi:10.1681/ASN.2018080832
  • Pergola PE, Rosenbaum DP, Yang Y, Chertow GM. A randomized trial of tenapanor and phosphate binders as a dual-mechanism treatment for hyperphosphatemia in patients on maintenance dialysis (AMPLIFY). J Am Soc Nephrol. 2021;32(6):1465–1473. doi:10.1681/ASN.2020101398
  • Shigematsu T, Une Y, Ikejiri K, Kanda H, Fukagawa M, Akizawa T. Therapeutic effects of add-on tenapanor for hemodialysis patients with refractory hyperphosphatemia. Am J Nephrol. 2021;52(6):496–506. doi:10.1159/000516156
  • Block GA, Bleyer AJ, Silva AL, et al. Safety and efficacy of tenapanor for long-term serum phosphate control in maintenance dialysis: a 52-week randomized Phase 3 trial (PHREEDOM). Kidney360. 2021;2(10):1600–1610. doi:10.34067/KID.0002002021
  • Luo H, Feng J, Zhang Y, et al. Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: a systematic review and meta-analysis of randomized placebo-controlled trials. Ther Apher Dial. 2023;27(5):839–847. doi:10.1111/1744-9987.14028