When treating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis,

How has the science around phosphate absorption advanced?

Consistently achieving target phosphorus levels with diet, dialysis, and phosphate-lowering medications has been a longtime challenge.

But with a deeper mechanistic understanding of phosphate absorption and the role of the paracellular pathway, Ardelyx has developed a new approach to advance patient care.

Most patients are unable to consistently achieve target phosphorus levels1,2
fishbane
Hear Dr. Glenn Chertow explain how we may be underestimating the magnitude of the problem

Even with management through diet, dialysis, and medication, many patients have been unable to maintain target phosphorus levels

42%
of patients have phosphorus >5.5 mg/dL1
77%
of patients are unable to consistently maintain phosphorus levels ≤5.5 mg/dL2
Demonstrated in a 2019 chart audit including the records of 1,015 patients on dialysis and on phosphorus-lowering therapy, submitted by 159 nephrologists.1

Evaluating the proportion of patients above target in a single month may underestimate the magnitude of the problem.

Hyperphosphatemia is an independent risk factor for the high rates of cardiovascular morbidity and mortality among patients with CKD on dialysis3-6

mortality risk graph serum phosphorus level mortality risk graph serum phosphorus level
cardiovascular hospitalization graph serum phosphorus level mortality risk graph serum phosphorus level
fishbane
Hear from Dr. Geoffrey Block about the cardiovascular consequences of hyperphosphatemia

Clinical practice guidelines for lowering elevated phosphate levels

KDOQI logo
In patients with CKD stage 5 and those treated with dialysis, the KDOQI guidelines (2003) recommend that serum levels of phosphorus should be maintained between 3.5 mg/dL–5.5 mg/dL7
Produced by the National Kidney Foundation, Inc.
All rights reserved.
kdigo logo
In patients with CKD G3a–G5D, the KDIGO guidelines (2017) recommend lowering elevated phosphate levels toward the normal range (2.5 mg/dL–4.5 mg/dL)8,9
Patients and healthcare providers discuss challenges managing phosphorus

What are the difficulties from the healthcare team’s perspective?

It’s important to point out that our inability to consistently achieve target phosphorus levels is not anybody’s fault. Patients are not to blame. Healthcare providers are not to blame. Look, I think we are all trying our best and that we have done the best we can with the tools that we have currently available to us.
But because of the limitations of these current strategies, controlling hyperphosphatemia remains challenging. We must revisit our current approach so that we can do better at managing this condition that is associated with significant cardiovascular risk to our patients.
Dr. Steven Fishbane
Chief of Nephrology
Northwell Health
fishbane
Hear from Dr. Steven Fishbane about challenges in the management of hyperphosphatemia
fishbane
Hear from a patient about managing her phosphorus

How do patients feel about managing their phosphorus?

Living with kidney disease has been a series of challenges. Phosphorus management has got to be one of the most challenging aspects of kidney disease, it has been an uphill battle. I have had kidney disease for 30 years and it’s still an uphill battle.
Dawn, a patient living with kidney disease for 30 years

Looking deeper into the science of phosphate absorption has revealed the primacy of the paracellular pathway

Our knowledge around phosphate absorption has evolved
As the science of intestinal phosphate absorption advances, it is becoming more evident that the paracellular pathway is the primary mechanism by which phosphate absorption occurs in humans. This new mechanistic understanding has important implications for the management of hyperphosphatemia.
Dr. Stuart Sprague
Chief, Division of Nephrology and Hypertension
Northshore University HealthSystem
fishbane
Hear from Dr. Stuart Sprague about our new mechanistic understanding of phosphate absorption

The paracellular pathway is the primary mechanism of phosphate absorption. Targeting this pathway may provide a valuable means of mediating phosphate absorption in the GI tract10-12

Dietary phosphate absorption occurs via 2 distinct intestinal pathways10,11
  • 1
    Paracellular absorption occurs passively along concentration gradients through tight junction complexes between cell membranes.10,11
    • The paracellular pathway is responsible for the bulk of phosphate absorption and does not appear to saturate12-14
  • 2
    Transcellular transport is active movement via carrier or transporter proteins through cell membranes. 10,11
    • While transcellular transport via NaPi2b plays an important role in phosphorus absorption in rodents, it is less relevant in humans because this pathway saturates in the presence of the high amounts of phosphorus contained in the Western diet
fishbane
Patients are at the forefront of everything we do
Ardelyx is committed to advancing the treatment of hyperphosphatemia in patients with CKD on dialysis