State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective

Although there is less evidence, clinical practice guidelines support “lowering elevated phosphate towards normal” in chronic kidney disease (CKD) glomerular filtration rate categories 3-5 (G3- G5). Potential strategies for these patients include reducing dietary phosphate intake and the use of binders.
The author Julia J. Scialla and colleagues published a paper in the American Journal of Kidney Disease under the title “State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective”. The summary of this paper is below:

Objective:

To discuss the current state of knowledge and evidence gaps for use of phosphate binders.
To emphasis the choice of phosphate-binding agents in CKD and kidney failure.

Method:

Currently available evidence on phosphate binder and scientific and medical knowledge for the same is used by authors.

Findings:

Phosphate-Binding Therapy
1) CKD G3-G5
• Clinically, rates of hyperphosphatemia remain normal until late CKD and are not evident until CKD G4.
• Along with the changes in bone, hyperphosphatemia also led to changes in many biochemical parameters associated with risks for cardiovascular disease and death.
• Trials found a similar result that urine phosphate excretion is largely affected by phosphate binders and not the serum levels of phosphate or its regulatory hormones.
• Surrogate outcomes (biochemical variables) can only provide initial proof-of-concept evidence for therapy as it proceeds through clinical development. Hence, guiding the patient with the support of this evidence is not recommended.
• Authors find a need for patient-centred and clinical outcome studies before the use of phosphate binders of any type can be recommended in CKD G3-G5 patients except to control symptomatic or severe hyperphosphatemia.

2) CKD G5D
• Phosphate binding results in favourable effects on many surrogate biochemical outcomes in CKD G5D.
• Binders affect serum phosphate levels and also normalize the phosphate-regulatory hormones PTH and FGF-23.
• In CKD G5D, hyperphosphatemia may become severe resulting in symptoms and well-described clinical complications such as calciphylaxis, bone disease, and itching. Hence, the use of binders to prevent clinically important hyperphosphatemia is justified.
• Authors find a need for trials focusing on the effect of intensive use of phosphate binders to specific targets aiming to prevent potential cardiovascular consequences.

Classes of Phosphate-Binding Therapy
• Commonly used calcium-based binders include calcium carbonate and calcium acetate.
• Non–calcium-based binders include lanthanum carbonated, sevelamer-based binders, sucroferric oxyhydroxide, and ferric citrate
• Sevelamer-based binders lower serum phosphate levels, serum cholesterol levels, and inflammatory markers
• Lanthanum carbonate has similar effects to other binders.
• Clinical trials evaluating the benefits of sevelamer-based or lanthanum carbonate versus placebo have never been conducted.
• Ferric citrate has an additional advantage in improving iron homeostasis in CKD, it helps to reduce the use of intravenous iron and erythropoiesis-stimulating agents and hence resulting in net cost saving. Ferric citrate also helps to lower FGF-23 levels.

Guideline Recommendations Related to Calcium Intake from Phosphate Binders
• Clinical practice guidelines recommended restriction of calcium from phosphate binders in CKD patients.
• As per the newly published KDOQI guideline on nutrition in CKD, total elemental calcium intake, including calcium supplementation, dietary calcium, and calcium-based phosphate binders, should be restricted to 800 to 1,000 mg/d for patients with CKD G3-G4 to maintain a neutral calcium balance. Additionally, adjustment of calcium intake to avoid hypercalcemia in CKD G5D is suggested.

Beyond Binders in Phosphate Management
• Other CKD-MBD therapies to affect phosphate management in addition to phosphate binders are as follow:
• Medical nutrition therapy, that provides phosphate-focused education can improve adherence to dietary restrictions, including phosphate.
• Pharmacologically, the use of calcimimetics over active vitamin D for the treatment and control of secondary hyperparathyroidism affects phosphate control
• Adjusting dialysis duration and frequency
• While some short-term studies are available on tenapanor, an experimental luminal blocker of sodium hydrogen exchange, it is still in phase 3 studies. It has been recently found to lower paracellular phosphate transport in the gut as an indirect effect.

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