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Phosphorus Phocus: Expanding the Hyperphosphatemia Toolkit

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Phosphorus Phocus:Expanding the Hyperphosphatemia Toolkit in Dialysis

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Supported by:

Index

Introduction

Traditonal approaches to phsphorus magement in dialysis

Treatment targets in dialysis

Practical considerations for clinical use

Patient Case Vignettes

Introducing the phosphate blocker: Exphozah (tenapanor)

Conclusion

References

Survey/Feedback

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Introduction

Phosphate abnormalities, which may occur in all stages of chronic kidney disease (CKD), increase with the severity of kidney dysfunction. Body phosphate homeostasis is determined by modulation of intestinal uptake of dietary phosphate, phosphate reabsorption and excretion by the kidneys, and the exchange of phosphate between extracellular and bone storage pools (Figure 1). 1,2

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Figure 1: Main regulators of phosphate metabolism

Primary source of phosphate

Diet

Increased intestinal phosphate absorption

Calcitriol

Increaseses skeletal phsphate resoption
Decreases kidney phphate reabsorption
Stimulates calcitriol production

Parathyroid Hormone PTH)

Phophatonins(e.g. FGF-23)

Increases kidney phosphate excretion
Inhibits PTH secretion

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Relationship between serum phosphate and EGFR

As the estimated glomerular filtration rate (eGFR) declines, the kidneys lose the ability to excrete phosphate. Excess phosphate retention occurs even though serum phosphate levels are often maintained within the normal reference range until late stages of CKD.3,4 Elevated serum phosphate levels do not become evident until GFR approaches 30 mL/min/1.73m2 or lower (Figure 2).5,6

Acknowledgement: Inker LA, Grams ME, Levey AS, et al. Relationship of estimated GFR and albuminuria to concurrent laboratory abnormalities: an individual participant data meta-analysis in a global consortium. Am J Kidney Dis. 2018;73(2):206-217. © 2018 by the National Kidney Foundation, Inc. All rights reserved.

Figure 2. Associations between eGFR, PTH, and Serum Phosphorus

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Hyperphophatemia Prevalence in Patients ESKD on Dialysis

Chronic hyperphosphatemia affects the majority of patients with ESKD on dialysis and is associated with significant negative clinical consequences, including vascular calcification, cardiovascular disease, left ventricular hypertrophy, bone loss, fractures, and mortality.8–13 Despite decades of clinical awareness and the availability of dietary interventions, phosphate binders, and dialysis-based clearance strategies, phosphate management is steadily worsening (Figure 3).14

Figure 3. Percentae of patients receiving dialysis with serum phsphorus ≥5.5 mg/dL

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Treatment targets in dialysis

For patients with stage G5D CKD, contemporary guidelines recommend targeting the lowering of serum phosphate levels “toward the normal range” rather than strict normalization, while also avoiding overt hyperphosphatemia and hypercalcemia, reaffirmed during a 2023 KDIGO controversies conference on chronic kidney disease-mineral and bone disorder (CKD-MBD).13,15,16

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Figure 4. Overview of TARGET & EPISODE trials

Intervention: calcium bicarbonate
Duration: 26 weeks
Intensive goal: 2.33-4.66 mg/dL (n=53)
Liberalized goal: 6.20-7.75 mg/dL (n=51)

Target

Intervention: sucroferric oxyhydroxide or lanthanum carbonate (2x2 design)
Duration: 12 months
Strict goal: 3.5-4.5 mg/dL (n=58)
Standard goal: 5.9-6.0 mg/dL (n=57)

Episode

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Treatment targets in dialysis: Emerging Evidence

As a result, two additional trials were initiated to further investigate whether targeting a lower phosphate level in patients on dialysis provides broader clinical benefits (e.g., mortality, hospitalization, cardiovascular events), with both leveraging a pragmatic randomized trial design (Table 1).18,19 Unfortunately, HiLo was terminated early due to the futility of enrollment and inadequate phosphate separation between groups, precluding inferences about the effects of specific phosphate targets on clinical outcomes.20 Alternatively, PHOSPHATE is currently underway, with study completion anticipated in late 2028.21 Of note, all of the PHOSPHATE study sites are outside the United States, including Australia, Canada, and the UK.

Table 1. Overview of HiLo & PHOSPHATE trials

Pertinent characteristics

Trial

HiLo

Target enrollment: 4400 adult patient with CKD G5D Treatment targets:

"Lo" (<5.5 mg/dL)
"Hi" ((≥6.5 mg/dL)

Intervention: phosphate-lowering therapies and dietary recommendations at the treating physician's discretion Primary endpoints: All-cause mortality & all-cause hospitalization

PHOSPHATE

Target enrollment: 3600 adult patient with CKD G5D Treatment targets:

Intensive (≤4.65 mg/dL)
Liberalized (6.2-7.75 mg/dL)

Intervention: phosphate-lowering therapies and dietary recommendations at the treating physician's discretion Primary endpoints: composite of CV death, non-fatal major CV or peripheral arterial events

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o Abbreviations: CKD G5D, stage G5 chronic kidney disease on dialysis; CV, cardiovascular; PLT, phosphate-lowering therapies.

Traditional Approaches to Phosphorus Management in Dialysis

The cornerstone of phosphate management in Stage G5D CKD is managing elevated phosphate levels and secondary hyperparathyroidism concurrently through a combination of limiting dietary phosphate intake, pharmacotherapy (e.g., phosphate-lowering agents, calcitriol/vitamin D analogues, calcimimetics), and customized dialysis settings.13,15,16,22 The decision regarding which approach(es) to use is highly dependent upon each patient’s individual metabolic status, comorbidities, side effect profiles, personal preferences and circumstances, and potential barriers to access. Additional factors to consider include restricting the dose of calcium-based phosphate binders in adults and basing treatment decisions on serial assessments of phosphate, calcium, and intact PTH levels considered together, rather than focusing on phosphate in isolation.

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Dietary Modifications

Subtitle

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o Acknowledgement: Biruete A, Hill Gallant KM, Lloyd L, Meade A, Moe SM, S. Jules DE, Kistler BM. ‘Phos’tering a clear message: the evolution of dietary phosphorus management in chronic kidney disease. J Ren Nutr. 2023;33(6S):S13-S20. © 2023 by the National Kidney Foundation, Inc. All rights reserved.

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Phosphate Binders

While there is insufficient evidence to support intensive phosphate binder use to achieve specific phosphate targets or to favor one agent over another, the risks associated with persistent untreated hyperphosphatemia must also be acknowledged and considered.30 Phosphate binders remain the primary pharmacologic treatment for hyperphosphatemia in patients on dialysis, with approximately 93% of Medicare-insured patients with ESKD prescribed one in 2019 (Table 2).30–32 Among the calcium-free binders, comparative efficacy and effects on hard clinical outcomes remain unclear.15,33 Overall, these agents demonstrate similar safety and efficacy, but differing side effect profiles, pleotropic effects, and dosage forms.30,33 These differences allow treatment plans to be individualized based on patient preferences, concurrent conditions, and tolerability using shared decision-making principles.22 Overall, phosphate binders are often associated with substantial treatment burden, which contributes to nonadherence. Up to 57% of US patients report skipping at least one dose per month.34 Many patients also experience inadequate phosphate control despite maximal binder therapy, highlighting the need for alternative or adjunctive approaches.

Table 2. Overview of phosphate binders currently available in the US

Introducing the Phosphate Blocker: Xphozah (tenapanor)

Xphozah (tenapanor) is a first-in-class phosphate absorption inhibitor (PAI) and FDA-approved to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy for patients who have an inadequate response to phosphate binders or are intolerant of any dose of phosphate binder therapy.35 Xphozah (tenapanor) is administered as one small 30 mg tablet taken twice daily, just before the first and last meals of the day. While initially developed for irritable bowel syndrome with constipation (marketed as Ibsrela), its phosphate-lowering properties led to development and approval for hyperphosphatemia management in patients on dialysis (marketed as Xphozah). Rather than bind dietary phosphates to prevent absorption, Xphozah (tenapanor) acts locally in the gut (with minimal systemic absorption) to inhibit the sodium-hydrogen exchanger 3 (NHE3), thereby significantly reducing phosphate absorption via the nonsaturable paracellular pathway (Figure 6).36

Figure 6. Dietary Phosphorus Absorption via Transcellular & Paracellular Pathways

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Acknowledgement: Yee J, Rosenbaum D, Jacobs JW, Sprague SM. Small intestinal phosphate absorption: novel therapeutic implications. Am J Nephrol. 2021;52(7):522-530. CC BY-NC

Mechanism of Action

Dietary phosphorus is primarily absorbed through the paracellular pathway, which accounts for approximately 65-80% of total phosphate absorption.3,37 This passive process occurs along concentration gradients through tight junction complexes between intestinal cells and increases linearly as phosphate concentration rises, rather than reaching a saturation point.3 By targeting paracellular phosphate transport, the mechanism of Xphozah (tenapanor) differs fundamentally from phosphate binders, which sequester phosphate within the intestinal lumen. Because Xphozah (tenapanor) acts continuously throughout the day while present in the gastrointestinal tract, it may provide more consistent phosphorus control, especially as an added layer of protection against “hidden phosphorus” in snacks and medications, which can be difficult to address with traditional phosphate binders.38 In addition to reducing paracellular phosphate absorption, Xphozah (tenapanor) also decreases expression of sodium-dependent phosphate transporter 2B (NaPi2b), the primary active intestinal phosphate transporter, thereby limiting compensatory increases in active transcellular phosphate absorption (Figure 7).36,39 Together, these effects on passive and active phosphate transport pathways contribute to the overall phosphate-lowering efficacy of Xphozah (tenapanor).

Figure 7. Modes of phosphate absorpotion & strategies to manage hyperphosphatemia

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Acknowledgement: Hill Gallant KM, Sprague SM, Rosenbaum DP, Spiegel DM, Kozuka K, Edelstein S, Chertow GM. Tenapanor: a phosphate absorption inhibitor for the management of hyperphosphatemia in patients with kidney failure. J Ren Nutr. 2025;35(1):25-34. CC BY-NC-ND 4.0

Clinical Trial Experience

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AMPLIFY

PHREEDOM

NORMALIZE

OPTIMIZE

2025 Meta-analysis

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Safety Considerations

The safety profile of Xphozah (tenapanor) has been evaluated in more than 750 patients with CKD on dialysis across multiple clinical trials, with exposure durations ranging from 4 weeks to over 1 year.39

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Practical Considerations for Clinical Use

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Mitigating Diarrhea Risk

Dosage and Administration

Patient Access

Patient Selection

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Practical Considerations for Clinical Use

Given that diarrhea is the most common adverse effect, proactive management strategies are essential:

Patient Education

Stop concurent laxatives

Dose reduction or discontinuation

Consider adding loperamide

Consider a dose titration

Skip before dialysis

Monitoring

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Dosage and Administration

Click each button below to learn more.

30 mg orally twice daily
Take just prior to the first and last meals ofthe day
Administering 5-10 minutes before a meal increases phosphorus excretion

Dosing

Serum phosphorus levels
Adjust Xphozah dosage as needed to anage GI tolerability
Reduce phosphate binder dosage as needed for hypophosphatemia

Monitoring

Skip the Xphozah dose right before hemodialysis session
Resume with the next regularly scheduled dose

Dialysis days

Skip the missed dose
Do not take two doses at the same time
Resume with the next regularly scheduled dose

Missed doses

Store in a dry place, protected from moisture
Keep in original bottle with desiccant and keep tightly closed

Storage

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Patient Selection

Click each button below to learn more.

Inadequate phosphate control despite binders

Phosphate Binder Intolerance

Constipation

High pill burden

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Patient Access

Unlike phosphate binders distributed by dialysis organizations or traditional prescriptions filled at any local community pharmacy, Xphozah (tenapanor) is distributed through a specialty pharmacy network. Prescriptions can be e-prescribed, faxed, or called in to a participating pharmacy within the Xphozah specialty pharmacy network. When sending the prescription, remember to include the dialysis center name, recent serum phosphorus labs, and brief binder history on the prescription. Also, inform your patients that they will need to respond to a call or text from the specialty pharmacy or ArdelyxAssist for their prescription to be processed. This interaction is essential for confirming consent, affordability, and shipping address. Once submitted, a benefits investigation is conducted to assess insurance coverage, prior authorization requirements, and anticipated out-of-pocket costs. If coverage barriers are encountered, ArdelyxAssist may support prior authorization submissions, appeals, and alternative access pathways (e.g., copay assistance, patient assistance). The manufacturer access team and specialty pharmacies may also assist with troubleshooting delays, resolving denials, and maintaining communication with patients and providers to ensure timely initiation of treatment. Once access is secured, patient onboarding and medication dispensing occur, usually via direct-to-patient shipment from the specialty pharmacy. More information can be found on the Xphozah website: https://www.xphozah-hcp.com/access-affordability/.

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Patient Case Vignettes

Review each case and answer the questions that follow.

cASE VIGNETTE 1

cASE VIGNETTE 2

cASE VIGNETTE 4

cASE VIGNETTE 3

cASE VIGNETTE 5

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Case Vignette 1

A 58-year-old woman with ESKD on peritoneal dialysis presents for routine follow-up. Her serum phosphorus is 7.2 mg/dL despite taking sevelamer carbonate 2400 mg three times daily with meals (9 tablets per day). She reports difficulty swallowing the large tablets and admits to frequently missing doses because "there are just too many pills." She also takes medications for hypertension, diabetes, peripheral neuropathy, and cardiovascular disease, bringing her total daily pill count to over 20 tablets. Her serum calcium is 9.5 mg/dL, and she has no history of gastrointestinal disorders. She reports chronic constipation requiring daily laxative use.

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Case Vignette 1: What Now?

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Case Vignette 1: Rationale

This patient is an ideal candidate for tenapanor therapy. She has inadequate phosphorus control despite phosphate binders, struggles with pill burden leading to poor adherence, and has chronic constipation. Adding tenapanor to her regimen addresses multiple issues: it provides additional phosphorus lowering through a complementary mechanism (NHE3 inhibition, reducing paracellular phosphate absorption), dramatically reduces overall pill burden compared to increasing her sevelamer dose, and may improve her constipation (don’t forget to educate the patient to stop her laxative when starting tenapanor!). Option A would worsen pill burden (adding 3 more large tablets daily), likely further reducing adherence. Option B may reduce pill burden but introduces calcium loading, which current guidelines recommend restricting to avoid vascular calcification. While emphasizing adherence is important, this patient is clearly struggling and noted the high pill burden as the specific cause for missed doses, making Option D insufficient to achieve any meaningful change.

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Case Vignette 2

A 33-year-old woman with ESKD on hemodialysis has serum phosphorus levels consistently fluctuating in and out of range over the past year. She reports trying her best with adherence to medications and limiting phosphorus in her diet, while also noting that childcare responsibilities for her 2 young children and juggling competing priorities can often get in the way. Her current serum phosphorus is 8.1 mg/dL despite maximal doses of lanthanum carbonate 1000 mg three times daily. Her serum calcium is 9.3 mg/dL. She reports no diarrhea but does experience occasional constipation. She has no history of bowel obstruction or inflammatory bowel disease.

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Case Vignette 2: What Now?

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Case Vignette 2: Rationale

This patient has likely maximized her current approaches to managing hyperphosphatemia, including dietary modification and maximal doses of phosphate binders, making her an ideal candidate for dual-mechanism therapy with tenapanor added to her existing binder. Tenapanor works through a distinct mechanism (reducing paracellular phosphate absorption via NHE3 inhibition) that is complementary to phosphate binders (which bind luminal phosphate). The AMPLIFY trial specifically demonstrated that adding tenapanor to existing phosphate binders in patients with inadequate phosphorus control achieved significantly greater phosphorus reduction compared to binders alone.Option A (switching binders) is unlikely to provide additional benefit as different phosphate binders have similar efficacy and mechanisms. Option C may provide modest additional phosphorus removal but is less practical and may not be sufficient. Option D introduces another agent with the same overall mechanism of action in addition to calcium loading, which guidelines recommend restricting.

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Case Vignette 3

A 71-year-old man with ESKD on hemodialysis presents with worsening hyperphosphatemia (serum phosphorus 7.8 mg/dL) despite taking calcium acetate. He has a complex medical history, including established cardiovascular disease with evidence of vascular calcification, and recurrent episodes of small bowel obstruction (most recent episode was 3 months ago, requiring hospitalization and nasogastric decompression). CT imaging at that time showed multiple areas of small bowel narrowing, likely from adhesions from prior abdominal surgeries. He is currently asymptomatic from a gastrointestinal standpoint but reports taking 15 different medications daily and would like to reduce his pill burden.

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Case Vignette 3: What Now?

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Case Vignette 3: Rationale

This patient has a history of recurrent small bowel obstruction with documented bowel narrowing, which represents a contraindication to tenapanor therapy. The FDA label explicitly states that tenapanor is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Even though the patient is currently asymptomatic, his anatomic abnormalities and history of recurrent obstruction create ongoing risk. Switching to a non-calcium phosphate binder like sevelamer or lanthanum carbonate is the most appropriate option to avoid calcium loading while providing effective phosphorus control without the contraindication with tenapanor. Option C (continuing calcium-based binders) is suboptimal given current guideline recommendations to limit the use of calcium-based binders, especially given this patient’s evidence of vascular calcification. Options A and D are both contraindicated regardless of dose due to his mechanical bowel issues.

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Case Vignette 4

A 54-year-old woman with ESKD on peritoneal dialysis was started on tenapanor 30 mg twice daily three weeks ago for persistent hyperphosphatemia (baseline serum phosphorus 7.4 mg/dL) despite sevelamer therapy. Her most recent serum phosphorus is 6.1 mg/dL, showing good response. However, she calls the clinic to report loose stools 3-4 times daily for the past two weeks. She describes the diarrhea as bothersome, but “not severe”. She has been taking the medication as prescribed (just before breakfast and dinner) and has not been using any laxatives or stool softeners. She denies abdominal pain, fever, blood in her stools, or signs of dehydration.

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Case Vignette 4: What Now?

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Case Vignette 4: Rationale

This patient is experiencing mild-to-moderate diarrhea from tenapanor, which is the most common adverse effect (occurring in 43-53% of patients) due to the medication’s mechanism of increasing intestinal sodium and water content. The appropriate management involves dose reduction rather than discontinuation, as she is achieving a good response to treatment and the diarrhea is not severe. Studies show that most diarrhea events are mild-to-moderate and can be managed with dose reduction.Option A is too aggressive; discontinuation is only recommended for severe diarrhea, particularly if associated with dehydration or hyponatremia (which occurs in less than 1% of patients). Her diarrhea is mild-to-moderate, and she's responding well to therapy. Adding loperamide (Option C) could be a potential follow-on option after decreasing the dose, but likely not appropriate for the patient’s current frequency of loose stools (3-4 times daily for 2 consecutive weeks). Lastly, taking tenapanor after meals rather than just before meals reduces its efficacy without any demonstrable benefit on reducing GI symptoms.

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Case Vignette 5

A 38-year-old man with ESKD secondary to IgA nephropathy started hemodialysis 6 weeks ago. His most recent labs show serum phosphorus of 6.2 mg/dL and serum calcium of 9.4 mg/dL. He has not yet started on any phosphate-lowering therapy. He works full-time as a software engineer and is highly motivated to manage his kidney disease. He reports excellent dietary adherence and has been working closely with a kidney dietitian on his low-phosphorus diet. He has a history of chronic diarrhea-predominant irritable bowel syndrome (IBS-D) that has been well-controlled on a low-FODMAP diet for the past year, with 1-2 loose stools daily at baseline. He is concerned about pill burden as he already takes multiple medications and asks about tenapanor, which he read about online as a "low pill burden option."

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Case Vignette 5: What Now?

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Case Vignette 5: Rationale

While tenapanor is not overtly contraindicated in this patient (he has no mechanical bowel obstruction), he is not an appropriate candidate for several important reasons. First, he has not yet tried first-line phosphate binder therapy. The FDA-approved indication for tenapanor is specifically as an add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. Since this patient has never been on a phosphate binder, tenapanor would not be appropriate first-line therapy. Second, his history of IBS-D with chronic diarrhea makes him a poor candidate for tenapanor, whose most common adverse effect is diarrhea occurring in 43-53% of patients. While not an absolute contraindication, initiating a medication that causes diarrhea in a patient with baseline diarrheal symptoms would likely result in poor tolerability and quality of life. The mechanism of tenapanor (NHE3 inhibition leading to increased intestinal sodium and water content) would predictably worsen his baseline loose stools. Third, his phosphorus level of 6.2 mg/dL is only modestly elevated and may respond well to first-line phosphate binder therapy, especially given his excellent dietary adherence and motivation. Option A overlooks both the FDA indication and his clinical history of diarrhea. Option B, while acknowledging the diarrhea risk with dose reduction, still inappropriately uses tenapanor as first-line therapy. Option D is inappropriate because his phosphorus is elevated while on dialysis despite working closely with a kidney dietitian and following the dietary recommendations. A low-phosphorus diet alone is generally insufficient for phosphorus control in patients on dialysis.

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Conclusion

In conclusion, tenapanor represents a valuable addition to the therapeutic toolbox for managing hyperphosphatemia in patients on dialysis. Its novel mechanism of reducing paracellular phosphate absorption through NHE3 inhibition, demonstrated efficacy for lowering serum phosphorus, a favorable long-term safety profile, and the potential to dramatically reduce pill burden make it an important option for patients with inadequate response to or intolerance of traditional phosphate binders. While diarrhea remains a common adverse effect requiring careful patient counseling and monitoring, most patients tolerate the medication well, and many experience the additional benefit of improved bowel function. As clinicians gain more experience with tenapanor, it is likely to play an increasingly important role in personalized approaches to CKD-MBD management. For patient-oriented information regarding hyperphosphatemia, be sure to visit: https://kidney.org/phosphate

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References

Felsenfeld AJ, Levine BS, Rodriguez M. Pathophysiology of Calcium, Phosphorus, and Magnesium Dysregulation in Chronic Kidney Disease. Semin Dial. 2015;28(6):564-577. doi:10.1111/sdi.12411

01

Goretti Penido M, Alon US. Phosphate homeostasis and its role in bone health. Pediatr Nephrol Berl Ger. 2012;27(11):2039-2048. doi:10.1007/s00467-012-2175-z

02

Yee J, Rosenbaum D, Jacobs JW, Sprague SM. Small Intestinal Phosphate Absorption: Novel Therapeutic Implications. Am J Nephrol. 2021;52(7):522-530. doi:10.1159/000518110

03

Kates DM, Sherrard DJ, Andress DL. Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure. Am J Kidney Dis Off J Natl Kidney Found. 1997;30(6):809-813. doi:10.1016/s0272-6386(97)90086-x

04

Craver L, Marco MP, Martinez I, et al. Mineral metabolism parameters throughout chronic kidney disease stages 1-5--achievement of K/DOQI target ranges. Nephrol Dial Transplant. 2007;22(4):1171-1176. doi:10.1093/ndt/gfl718

05

Ketteler M. Phosphate Metabolism in CKD Stages 3-5: Dietary and Pharmacological Control. Int J Nephrol. 2011;2011:970245. doi:10.4061/2011/970245

06

07

Waziri B, Duarte R, Naicker S. Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD): Current Perspectives. Int J Nephrol Renov Dis. 2019;12:263-276. doi:10.2147/IJNRD.S191156

08

Düsing P, Zietzer A, Goody PR, et al. Vascular pathologies in chronic kidney disease: pathophysiological mechanisms and novel therapeutic approaches. J Mol Med Berl Ger. 2021;99(3):335-348. doi:10.1007/s00109-021-02037-7

09

Xu C, Smith ER, Tiong MK, Ruderman I, Toussaint ND. Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials. J Am Soc Nephrol. 2022;33(5):1011-1032. doi:10.1681/ASN.2021101327

Viegas C, Araújo N, Marreiros C, Simes D. The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): challenging old concepts with new facts. Aging. 2019;11(12):4274-4299. doi:10.18632/aging.102046

10

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References

Reiss AB, Miyawaki N, Moon J, et al. CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies. Atherosclerosis. 2018;278:49-59. doi:10.1016/j.atherosclerosis.2018.08.046

11

London GM, Guérin AP, Marchais SJ, Métivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2003;18(9):1731-1740. doi:10.1093/ndt/gfg414

12

Ketteler M, Evenepoel P, Holden RM, et al. Chronic kidney disease–mineral and bone disorder: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2025;107(3):405-423. doi:10.1016/j.kint.2024.11.013

13

Unites States Renal Data System Annual Data Report. End Stage Renal Disease - Chapter 2: Clinical Indicators and Preventative Care. In: 2025 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2025. Accessed April 14, 2026. https://usrds-adr.niddk.nih.gov/2025/end-stage-renal-disease/2-clinical-indicators-and-preventive-care

14

Isakova T, Nickolas TL, Denburg M, et al. KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Am J Kidney Dis. 2017;70(6):737-751. doi:10.1053/j.ajkd.2017.07.019

15

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. doi:10.1016/j.kisu.2017.04.001

16

17

Isaka Y, Hamano T, Fujii H, et al. Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients. J Am Soc Nephrol JASN. 2021;32(3):723-735. doi:10.1681/ASN.2020050598

18

Edmonston DL, Isakova T, Dember LM, et al. Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis. Am J Kidney Dis Off J Natl Kidney Found. 2021;77(6):920-930.e1. doi:10.1053/j.ajkd.2020.10.008

19

National Library of Medicine. Pragmatic Randomised Trial of High Or Standard PHosphAte Targets in End-stage Kidney Disease (PHOSPHATE). Published online May 10, 2024. Accessed September 19, 2024. https://clinicaltrials.gov/study/NCT03573089

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Edmonston D, Isakova T, Dember LM, et al. Higher versus Lower Phosphate Targets for Patients Undergoing In-Center Hemodialysis: A Randomized Controlled Trial. J Am Soc Nephrol JASN. 2025;36(12):2445-2455. doi:10.1681/ASN.0000000765

20 References

University of Queensland. Pragmatic Randomised Trial of High Or Standard PHosphAte Targets in End-stage Kidney Disease (PHOSPHATE) (PHOSPHATE). July 1, 2025. Accessed April 17, 2026. https://clinicaltrials.gov/study/NCT03573089

21

Hu L, Napoletano A, Provenzano M, et al. Mineral Bone Disorders in Kidney Disease Patients: The Ever-Current Topic. Int J Mol Sci. 2022;23(20):12223. doi:10.3390/ijms232012223

22

Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am J Kidney Dis Off J Natl Kidney Found. 2020;76(3 Suppl 1):S1-S107. doi:10.1053/j.ajkd.2020.05.006

23

Kistler BM, Moore LW, Benner D, et al. The International Society of Renal Nutrition and Metabolism Commentary on the National Kidney Foundation and Academy of Nutrition and Dietetics KDOQI Clinical Practice Guideline for Nutrition in Chronic Kidney Disease. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found. 2021;31(2):116-120.e1. doi:10.1053/j.jrn.2020.05.002

24

Biruete A, Hill Gallant KM, Lloyd L, et al. ’Phos’tering a Clear Message: The Evolution of Dietary Phosphorus Management in Chronic Kidney Disease. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found. 2023;33(6S):S13-S20. doi:10.1053/j.jrn.2023.05.004

25

Kalantar-Zadeh K, Gutekunst L, Mehrotra R, et al. Understanding sources of dietary phosphorus in the treatment of patients with chronic kidney disease. Clin J Am Soc Nephrol CJASN. 2010;5(3):519-530. doi:10.2215/CJN.06080809

26

27

Naber T, Purohit S. Chronic Kidney Disease: Role of Diet for a Reduction in the Severity of the Disease. Nutrients. 2021;13(9):3277. doi:10.3390/nu13093277

28

Chan W. Chronic Kidney Disease and Nutrition Support. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 2021;36(2):312-330. doi:10.1002/ncp.10658

29

Anderson CAM, Nguyen HA. Nutrition education in the care of patients with chronic kidney disease and end-stage renal disease. Semin Dial. 2018;31(2):115-121. doi:10.1111/sdi.12681

Scialla JJ, Kendrick J, Uribarri J, et al. State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective. Am J Kidney Dis Off J Natl Kidney Found. 2021;77(1):132-141. doi:10.1053/j.ajkd.2020.05.025

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References

Flythe JE, Watnick S. Dialysis for Chronic Kidney Failure: A Review. JAMA. 2024;332(18):1559. doi:10.1001/jama.2024.16338

31

32

Natale P, Green SC, Ruospo M, et al. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Central Editorial Service, ed. Cochrane Database Syst Rev. 2025;2025(6). doi:10.1002/14651858.CD006023.pub4

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

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Fissell RB, Karaboyas A, Bieber BA, et al. Phosphate binder pill burden, patient-reported non-adherence, and mineral bone disorder markers: Findings from the DOPPS. Hemodial Int Int Symp Home Hemodial. 2016;20(1):38-49. doi:10.1111/hdi.12315

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Xphozah (tenapanor) tablets. Published online June 2025. Accessed April 20, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/213931s005lbl.pdf

35

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

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Saurette M, Alexander RT. Intestinal phosphate absorption: The paracellular pathway predominates? Exp Biol Med Maywood NJ. 2019;244(8):646-654. doi:10.1177/1535370219831220

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Dwyer JP, Kelepouris E. New Directions in Phosphorus Management in Dialysis. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found. 2023;33(1):12-16. doi:10.1053/j.jrn.2022.04.006

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Hill Gallant KM, Sprague SM, Rosenbaum DP, et al. Tenapanor: A Phosphate Absorption Inhibitor for the Management of Hyperphosphatemia in Patients With Kidney Failure. J Ren Nutr. 2025;35(1):25-34. doi:10.1053/j.jrn.2024.07.003

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

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References

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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 JASN. 2021;32(6):1465-1473. doi:10.1681/ASN.2020101398

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Silva AL, Chertow GM, Hernandez GT, et al. Tenapanor Improves Long-Term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study. Kidney360. 2023;4(11):1580-1589. doi:10.34067/KID.0000000000000280

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Sprague SM, Weiner DE, Tietjen DP, et al. Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study. Kidney360. 2024;5(5):732-742. doi:10.34067/KID.0000000000000387

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Khan LA, Alam B, Ladhwani NK, et al. Efficacy and Safety of Tenapanor in Hemodialysis Patients with Hyperphosphatemia: A Systematic Review and Meta-Analysis of Short-Term Randomized Controlled Trials. Am J Nephrol. Published online July 9, 2025:1-12. doi:10.1159/000546265

Akizawa T, Urano N, Ikejiri K, Nakanishi K, Fukagawa M. Tenapanor: A novel therapeutic agent for dialysis patients with hyperphosphatemia. Ther Apher Dial Off Peer-Rev J Int Soc Apher Jpn Soc Apher Jpn Soc Dial Ther. 2025;29(2):157-169. doi:10.1111/1744-9987.14241

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Fishbane S, Zhao S, Edelstein S, Yang Y, Spiegel D. Tenapanor-Treated Patients Using Over-the-Counter Antidiarrheal Agents Saw Decreased Stool Frequency and Improved Stool Consistency. Presented at: 2025 National Kidney Foundation Spring Clinical Meetings; April 2025; Boston, MA. Accessed April 20, 2026. https://cme.kidney.org/spa/app/resource/r649-2025-spring-clinical-meetings/event/home/posters/abstracts?abstractId=6732

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Phosphate binder intolerance

Xphozah (tenapanor) offers an alternative mechanism for patients who cannot tolerate adequate doses of phosphate binders due to gastrointestinal side effects or other adverse reactions.

AMPLIFY

In the subsequent AMPLIFY trial, patients treated with tenapanor plus binder therapy achieved a larger mean change in serum phosphate compared with placebo plus a binder over 4 weeks (-0.84 mg/dL vs -0.19 mg/dL, p<0.001, both from an average baseline of approximately 6.8 mg/dL), with 37.1% and 21.8% of patients achieving serum phosphorus concentrations <5.5 mg/dL respectively (p=0.01). The most commonly reported treatment-related adverse events were diarrhea (40.2% vs. 6.7%) and nausea (5.1% vs. 2.5%).41

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Stop concurent laxatives

Instruct patients to stop using stool softeners or laxatives while taking Xphozah (tenapanor), as these may exacerbate diarrhea. Patients should also be counseled not to start a laxative while using Xphozah (tenapanor).

High pill burden

OPTIMIZE demonstrated Xphozah (tenapanor) efficacy in reducing serum phosphate levels while also reducing pill burden by a median reduction in pill number of 16.7 (3 pills/day) and 44.4% (6 pills/day) in the binder reduction and straight switch groups, respectively. Furthermore, 84.4% of patients who completed a patient experience questionnaire reported an improvement in their phosphate management routine, with approximately 35% of respondents citing the size or number of phosphate-lowering pills as the most likely contributing factor.43

Done reduction or discontinuation

For moderate diarrhea, consider a dose reduction to 20 mg BID. For severe diarrhea, particularly if associated with dehydration or electrolyte abnormalities, discontinue treatment.

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Figure 3. Percentae of patients receiving dialysis with serum phsphorus ≥5.5 mg/dL

PHREEDOM

In the PHREEDOM trial, tenapanor administered twice daily (with a phosphate binder washout) significantly lowered serum phosphate in patients receiving maintenance dialysis, resulting in a mean reduction of -1.4 mg/dL from a baseline of approximately 7.4 mg/dL (p<0.0001).40

Consider a dose titration

While dose titration is not necessary to initiate Xphozah (tenapanor), patients or clinicians with significant concerns about diarrhea may consider starting at a lower dose (e.g., 20 mg twice daily), increasing to the target dose of 30 mg twice daily as tolerated to maximize its efficacy.

Figure 2. Associations between eGFR, PTH, and Serum Phosphorus

2025 Meta-analysis

In a 2025 meta-analysis of short-term randomized controlled trials (4-8 weeks), tenapanor demonstrated a mean reduction of -1.39 mg/dL (95% CI: -1.94, -0.84; p<0.0001) and an increased likelihood of achieving a target serum phosphate level ≤5.5 mg/dL (RR: 2.80; 95% CI: 1.70, 4.61; p<0.0001), both compared with placebo.44

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Diarrhea: Diarrhea is the most common adverse reaction, reported in 43-53% of patients, with severe diarrhea reported in ~5%.39 This is to be expected, given how inhibiting NHE3-mediated sodium absorption in the intestine increases stool sodium and water content, leading to softened stools or diarrhea.36 Diarrhea typically occurs soon after treatment initiation but can develop at any time during therapy.35 Most cases are mild to moderate and resolve over time or with dose reduction, while severe diarrhea may rarely lead to dehydration or hyponatremia (<1%). Accordingly, FDA labeling recommends discontinuing Xphozah (tenapanor) in patients who develop severe diarrhea.35

OPTIMIZE

OPTIMIZE was a randomized, open-label study evaluating different strategies for initiating tenapanor in patients on dialysis with uncontrolled hyperphosphatemia. Strategies included switching from phosphate binders to tenapanor (straight switch), reducing phosphate dosage by ≥50% and adding tenapanor (binder reduction), or starting tenapanor monotherapy (binder-naïve). After 10 weeks, 34.4% (straight switch), 38.2% (binder reduction), and 63.3% (binder-naïve) of patients achieved a serum phosphorus ≤5.5 mg/dL. These outcomes were observed despite a median reduction in total daily pill number of 44.4% (straight switch) and 16.7% (binder reduction) from baseline (median 9 pills per day). Among “straight switch” and “binder reduction” patients who completed patient experience questionnaires, 84.4% reported an improved phosphate management routine. Diarrhea was the most common adverse event, affecting 39.9% of patients, leading to tenapanor discontinuation in 6.6% of patients.43

Consider adding loperamide

For mild to moderate diarrhea, loperamide may help ameliorate diarrhea associated with Xphozah (tenapanor) and facilitate its continued use.46

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Patient Education

Inform patients that softened stools or mild diarrhea are expected due to the medication's mechanism of action, and it often improves over time.

Constipation

An additional benefit observed in clinical practice is improvement in constipation, which is common in dialysis patients. In the OPTIMIZE trial, 25.8% of patients who reported an improvement in their phosphate management routine cited their frequency of bowel movements as a significant contributing factor.43 This dual benefit may be particularly advantageous for patients on dialysis who often experience constipation from phosphate binders, opioid medications, and reduced physical activity.

Monitoring

Monitor for signs and symptoms of diarrhea, dehydration, and electrolyte abnormalities, particularly during treatment initiation and dose escalation. Advise patients to report severe diarrhea promptly, as treatment discontinuation may be necessary.

Skip before dialysis

Ensure patients skip their dose right before a dialysis session and instead take it right before the next meal following dialysis. This helps minimize the inconvenience and potential complications of diarrhea occurring during or immediately after dialysis treatments.

NORMALIZE

NORMALIZE, the 18-month open-label extension study for patients who completed the PHREEDOM study, used tenapanor and sevelamer carbonate (as needed) to maintain serum phosphate levels between 2.5 and 4.5 mg/dL. This trial found an overall mean reduction in serum phosphate of -2.0 mg/dL from PHREEDOM baseline to the end of NORMALIZE, and 33% of patients achieved phosphate levels within the target range.42

Other considerations: Beyond diarrhea, Xphozah (tenapanor) has demonstrated a favorable safety profile with no clinically significant laboratory abnormalities observed other than its intended effects on serum phosphorus.39,45 Its minimal systemic absorption limits the potential for systemic adverse effects.35 Xphozah (tenapanor) is contraindicated in patients with mechanical gastrointestinal obstruction and in patients under 6 years of age.35

Inadequate phosphate control despite binders

The AMPLIFY & OPTIMIZE trials demonstrated significant additional phosphate lowering when Xphozah (tenapanor) was added to existing binder therapy in patients with persistent hyperphosphatemia.41,43

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Phosphorus Phocus: Expanding the Hyperphosphatemia Toolkit

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Transcript

Phosphorus Phocus:Expanding the Hyperphosphatemia Toolkit in Dialysis

Supported by:

Index

Introduction

Traditonal approaches to phsphorus magement in dialysis

Treatment targets in dialysis

Practical considerations for clinical use

Patient Case Vignettes

Introducing the phosphate blocker: Exphozah (tenapanor)

Conclusion

References

Survey/Feedback

Introduction

Relationship between serum phosphate and EGFR

Hyperphophatemia Prevalence in Patients ESKD on Dialysis

Treatment targets in dialysis

Treatment targets in dialysis: Emerging Evidence

Traditional Approaches to Phosphorus Management in Dialysis

Dietary Modifications

Subtitle

Subtitle

Subtitle

Subtitle

Phosphate Binders

Table 2. Overview of phosphate binders currently available in the US

Introducing the Phosphate Blocker: Xphozah (tenapanor)

Mechanism of Action

Clinical Trial Experience

Safety Considerations

Practical Considerations for Clinical Use

Practical Considerations for Clinical Use

Dosage and Administration

Patient Selection

Patient Access

Patient Case Vignettes

Review each case and answer the questions that follow.

Case Vignette 1

Case Vignette 1: What Now?

Case Vignette 1: Rationale

Case Vignette 2

Case Vignette 2: What Now?

Case Vignette 2: Rationale

Case Vignette 3

Case Vignette 3: What Now?

Case Vignette 3: Rationale

Case Vignette 4

Case Vignette 4: What Now?

Case Vignette 4: Rationale

Case Vignette 5

Case Vignette 5: What Now?

Case Vignette 5: Rationale

Conclusion

Thank you!

References

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