Table 2.

Overview of current strategies to lower serum phosphate levels and potential drawbacks of each intervention

Strategy	Potential drawbacks of intervention
Dialysis	Dialysis carries a significant healthcare resource burden and has a marked impact on patients’ daily activities Three-times-weekly hemodialysis can remove only about 3 days’ worth of ingested phosphate, meaning a relatively large amount must be handled by dietary phosphate binders instead [50]
Dietary phosphate restriction	Achieving adequate dietary phosphate restriction can prove challenging in clinical practice [50, 53] Western diets have a high phosphate content, and marked restrictions can result in protein insufficiency [50] Patients often find they are unable to adhere to these regimens [53] Dietary phosphate restriction can lead to compensatory upregulation of NaPi2b-dependent phosphate transport [7, 9, 11–14]
Phosphate binders	Most effective when dietary phosphate intake is < 1000 mg/day; when phosphate intake is ≥ 2000 mg/day, effectiveness is reduced, and hyperphosphatemia may persist [53] Calcium overload is a serious potential consequence of calcium-based binder use [42]. Non-calcium-based binders can eliminate this risk, but may be associated with other adverse events, such as aluminum accumulation toxicity [114]. They may also be less cost-effective than calcium-based binders [115] High phosphate-binder doses are often required, which may lead to high tablet burdens and issues with gastrointestinal tolerability Phosphate-binder treatment can lead to compensatory upregulation of NaPi2b-dependent phosphate transport [10] High tablet burdens are associated with nonadherence to treatment [116, 117], which, in turn, is associated with poor phosphate control [116, 118, 119]
Controlling PTH levels	Calcimimetics can only lower the amount of phosphate mobilized from bone, limiting their effect to an estimated 3% reduction in serum phosphate concentration for every 10% reduction in PTH level [66]. This intervention is restricted to patients with additional hyperparathyroidism, who only make up about 40% of all patients with CKD stage 5D (dialysis-dependent)

CKD chronic kidney disease, NaPi2b sodium–phosphate cotransporter 2b, PTH parathyroid hormone