Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia

Abstract

Population-based studies have shown that most patients with advanced chronic kidney disease (CKD) do not have optimal phosphate levels. Meta-analyses suggest that there is a morbidity and mortality benefit associated with the lowering of serum phosphate levels. However, to date there is no conclusive evidence from randomized controlled trials (RCTs) that lowering serum phosphate levels reduces the risk of morbidity and mortality. However, hyperphosphatemia may pose a risk to patients and treatment should be considered. We therefore sought to conduct a multidisciplinary review to help guide clinical decision-making pending results of ongoing RCTs. Restricting dietary phosphate intake is frequently the first step in the management of hyperphosphatemia. Important considerations when proposing dietary restriction include the patient’s socioeconomic status, lifestyle, dietary preferences, comorbidities, and nutritional status. While dietary phosphate restriction may be a valid strategy in certain patients, serum phosphate reductions achieved solely by limiting dietary intake are modest and should be considered in conjunction with other interventions. Conventional dialysis is also typically insufficient; however phosphate removal may be augmented by increased frequency or duration of dialysis, or through enhanced methods such as hemodiafiltration. Phosphate binders have been shown to reduce absorption of dietary phosphate and lower serum phosphate levels. There are several phosphate binders available, and while they all lower phosphate levels to variable degrees, they differ with respect to their pill burden, potential to induce or exacerbate vascular calcification or ectopic calcification, tissue accumulation, safety, and tolerability. The widespread treatment of hyperphosphatemia requires convincing data from RCTs to ascertain whether lowering serum phosphate levels improves patient-important outcomes, as well as the optimal method and degree of phosphate control. In the interim, the decision and approach used to treat hyperphosphatemia should be based on the best available data, as well as patient needs and clinical judgment.

Intact FGF23 predicts serum phosphate improvement after combined nicotinamide and phosphate binder treatment in hemodialysis patients

“…Hyperphosphatemia, high fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) levels, and low calcitriol and soluble αKlotho levels in plasma are characteristic hallmarks of ESKF [ 2 , 3 ]. Hyperphosphatemia in ESKF is associated with a higher mortality and cardiovascular disease risk [ 4 , 5 ], and limited evidence suggests that reducing phosphate levels in ESKF patients may improve their outcome [ 6 , 7 ]. Current treatment is mostly focused on reducing intestinal phosphate absorption [ 8 ].…”

Clinical development and management of adverse events associated with FGFR inhibitors

“…Information on low-phosphate diets is widely available and should be discussed with the patient using a multidisciplinary approach. 40 The phosphate pyramid is a useful tool to illustrate the phosphate content of various foods to patients. 41 Examples of high-phosphate foods and low-phosphate alternatives are shown in Table S2 .…”

“… 42 Boiling, which reduces the phosphate content of food, can also be suggested as the preferred cooking technique. 40 …”

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study

“…The currently used phosphorus binders mainly fall into two categories: calcium-containing phosphorus binders and noncalcium phosphorus binders, such as sevelamer, lanthanum carbonate, aluminum-containing phosphate binders [11, 12]. Calcium-containing phosphorus binders, such as calcium carbonate, calcium acetate, and calcium citrate, are potent phosphate binders, but they may cause hypercalcemia, which leads to metastatic calcifications and hardening tissues affecting organ function [13, 14].…”