Evidence-based frameworks for identifying candidates for alternative phosphate management strategies
Integrating novel phosphate management approaches requires systematic frameworks for patient selection, treatment sequencing, and outcome monitoring.1,2 Disease severity, treatment tolerance, adherence capacity, and individual response patterns vary substantially, necessitating individualized therapeutic strategies.1 In addition to resistant hyperphosphatemia, patients reporting significant gastrointestinal side effects, those unable to manage high pill burden, and individuals with documented non-adherence related to medication complexity represent potential candidates for simplified regimens.3,4
Cardiovascular risk stratification may inform treatment intensity given established associations between hyperphosphatemia and cardiovascular outcomes.5,6 Patients with CKD have higher rates of coronary-artery disease, heart failure, stroke, valvular heart disease, arrhythmia, and sudden cardiac death than the general population, calling for consideration for more aggressive management.6
Initial management traditionally optimizes dialysis adequacy, provides intensive dietary education with dietitian involvement, and titrates first-line binders to maximum tolerated doses.7 For inadequate control or significant side effects, alternative binder selection represents typical second-line approach.
For patients with persistent hyperphosphatemia (typically defined as phosphate that remains above 5.5-6.0 mg/dL) despite optimized conventional therapy, mechanistically distinct approaches become appropriate. Inhibitors of active intestinal phosphate transport can address limitations of binder-only strategies and may be added to existing regimens or substituted when pill burden or intolerance restricts effective dosing.2 Emerging agents, including novel lanthanum-based formulations aimed at reducing pill burden, remain investigational pending regulatory review.8,9 Across all approaches, treatment decisions should be guided by ongoing assessment of biochemical control, symptom burden, and patient-reported outcomes to ensure that therapy aligns with individual goals and tolerability.
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Cernaro V, Longhitano E, Casuscelli C, Peritore L, Santoro D. Hyperphosphatemia in Chronic Kidney Disease: The Search for New Treatment Paradigms and the Role of Tenapanor. Int J Nephrol Renovasc Dis. 2024;17:151-161. Published 2024 May 28. doi:10.2147/IJNRD.S385826
Nitta K, Itoyama S, Ikejiri K, et al. Randomized Study of Tenapanor Added to Phosphate Binders for Patients With Refractory Hyperphosphatemia. Kidney Int Rep. 2023;8(11):2243-2253. Published 2023 Aug 13. doi:10.1016/j.ekir.2023.08.003
Nagano, N., Ito, K., Ono, T. et al.Prescription characteristics of phosphate binders in a high pill burden for hemodialysis patients. Ren Replace Ther 7, 5 (2021). https://doi.org/10.1186/s41100-021-00322-2
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
Pezeshgi A, Alemohammad Y, Tavasol A, et al. The Association Between the Levels of Serum Phosphate and Mortality Rates in Pre-Dialysis and Dialysis Patients. Indian J Nephrol. 2025;35(4):485-489. doi:10.25259/ijn_398_23
Nelson AJ, Raggi P, Wolf M, Gold AM, Chertow GM, Roe MT. Targeting Vascular Calcification in Chronic Kidney Disease. JACC Basic Transl Sci. 2020;5(4):398-412. Published 2020 Apr 27. doi:10.1016/j.jacbts.2020.02.002
[1] Vallée M, Weinstein J, Battistella M, Papineau R, Moseley D, Wong G. Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia. Int J Nephrol Renovasc Dis. 2021;14:301-311. Published 2021 Aug 6. doi:10.2147/IJNRD.S318593
[2] Pergola PE, Joy MS, Garsd A, et al. Safety and Phosphate-Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers. Clin Transl Sci. 2025;18(1):e70116. doi:10.1111/cts.70116
[3] Grossi G. Oxylanthanum Carbonate Fails to Secure FDA Approval for Hyperphosphatemia, CKD. Ajmc.com. Published June 30, 2025. Accessed December 4, 2025. https://www.ajmc.com/view/oxylanthanum-carbonate-fails-to-secure-fda-approval-for-hyperphosphatemia-ckd
[4] 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
[5] Pezeshgi A, Alemohammad Y, Tavasol A, et al. The Association Between the Levels of Serum Phosphate and Mortality Rates in Pre-Dialysis and Dialysis Patients. Indian J Nephrol. 2025;35(4):485-489. doi:10.25259/ijn_398_23
[6] Nelson AJ, Raggi P, Wolf M, Gold AM, Chertow GM, Roe MT. Targeting Vascular Calcification in Chronic Kidney Disease. JACC Basic Transl Sci. 2020;5(4):398-412. Published 2020 Apr 27. doi:10.1016/j.jacbts.2020.02.002
[7] Vallée M, Weinstein J, Battistella M, Papineau R, Moseley D, Wong G. Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia. Int J Nephrol Renovasc Dis. 2021;14:301-311. Published 2021 Aug 6. doi:10.2147/IJNRD.S318593
[8] Pergola PE, Joy MS, Garsd A, et al. Safety and Phosphate-Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers. Clin Transl Sci. 2025;18(1):e70116. doi:10.1111/cts.70116
[9] Grossi G. Oxylanthanum Carbonate Fails to Secure FDA Approval for Hyperphosphatemia, CKD. Ajmc.com. Published June 30, 2025. Accessed December 4, 2025. https://www.ajmc.com/view/oxylanthanum-carbonate-fails-to-secure-fda-approval-for-hyperphosphatemia-ckd
