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Pathway for the Management of Hyperphosphataemia in Adults with

Stage 4 or 5 Chronic Kidney Disease (CKD)

Rationale: Hyperphosphataemia (elevated serum phosphate) is recognised as an important risk factor for many adverse outcomes
in dialysis patients, including secondary hyperparathyroidism, renal bone disease, vascular calcification, calciphylaxis and mortality.
Retention of phosphate and the subsequent rise in serum phosphate can occur when the estimated glomerular filtration rate (eGFR)
falls below 30ml/min (CKD 4).
Aim: To maintain phosphate levels between 0.9-1.5mmol/l in patients with CKD4-5 who are not on dialysis and between 1.1 and
1.7mmol/l in dialysis patients (1).

Dietary Modification: Patients with CKD4-5 may need to follow a reduced phosphate diet. Phosphate rich foods include dairy
products, eggs, certain meat and fish, chocolate, nuts, cola drinks and many processed foods. Diets need to be balanced carefully
and so referral to a specialist renal dietitian is recommended.

Phosphate binders: If phosphate cannot be controlled within target range despite dietary phosphate restriction, then a phosphate
binder should be prescribed as per NICE guidelines (2):
FIRST LINE CHOICE: CALCIUM ACETATE
Calcium Acetate (Phosex® 1000mg or Renacet® 475mg/ 950mg) If calcium acetate is not tolerated or patients find
Indication: hyperphosphataemia it unpalatable consider using:
Calcium content: Phosex 250mg per tablet, Renacet 120.25mg per Calcium Carbonate (Calcichew® 1.25g or Adcal® 1.5g)
475mg tablet, 240.5mg per 950mg tablet Indication: hyperphosphataemia
Dose: Phosex: 1000mg tds with meals titrated according to serum Calcium content: Calcichew 500mg per tablet, Adcal 600mg per tablet
phosphate levels, max 12 tablets daily. Renacet: 1x950mg or 2x475mg Dose: To be titrated starting at 1 bd up to 2 tds with meals
tablets per meal, titrating up to max 6650mg daily. Side effects: hypercalcaemia
Side effects: nausea, vomiting, constipation, diarrhoea NB: D3 versions of calcium carbonate should not be used as
NB Prescribe in line with an effective shared care agreement (ESCA) phosphate binders in patients with CKD4-5. If already prescribed,
calcium acetate.doc check indication for use.

SECOND LINE CHOICES: NON-CALCIUM BASED PHOSPHATE BINDERS


Consider switching to or combining with a non-calcium based binder if:
- calcium based phosphate binders are not well tolerated
- serum phosphate remains high despite maximum recommended (or tolerated) daily dose of calcium based binders
- serum calcium goes above the upper limit of normal (2.5mmol/l), after addressing other potential causes
- serum parathyroid hormone (PTH) is low, after addressing other potential causes

Sevelamer carbonate Sevelamer hydrochloride Sucroferric oxyhydroxide Lanthanum carbonate hydrate


(Renvela® and generic 800mg) (Renagel® 800mg) (Velphoro® 500mg) (3) (Fosrenol®
- Indication: - Indication: - Indication: 500mg/750mg/1000mg)
hyperphosphataemia in hyperphosphataemia in hyperphosphataemia in - Indication:
dialysis patients and CKD haemodialysis and peritoneal dialysis patients. hyperphosphataemia in
patients not on dialysis if dialysis patients. - Dose: 500mg tds with meals, dialysis patients. Can be used
phosphate ≥1.78mmo/l. - Dose: 1 tds with meals titrated titrated up to max 3000mg (6 in CKD patients not on dialysis
- Dose: 1 tds with meals titrated to max 5 tablets per meal. tablets) per day if phosphate ≥1.78mmo/l
to max 5 tablets per meal. - Side effects: nausea, - Side effects: diarrhoea, - Dose: 500mg, 750mg or
- Side effects: nausea, vomiting, diarrhoea, discoloured faeces, nausea, 1000mg with meals titrated to
vomiting, diarrhoea, constipation, abdominal pain, constipation, vomiting, 1500mg or 3000mg daily.
constipation, abdominal pain, dyspepsia, flatulence. dyspepsia, abdominal pain, - Side effects: nausea, vomiting,
dyspepsia, flatulence. - NB: Prescribe in line with an flatulence. diarrhoea, constipation,
- NB: Prescribe in line with an ESCA sevelamer.doc - NB: Prescribe in line with an abdominal pain.
ESCA sevelamer.doc ESCA - NB: Prescribe in line with an
Sucroferricoxyhydroxide.doc ESCA lanthanum.doc

Important considerations when prescribing phosphate binders:

- Advise the patient that it is essential to take phosphate binders with food, ideally with all of their meals.
- Consider patient preference, ease of administration, compliance and tablet burden.
- If a combination of phosphate binders is used, titrate the dosage to achieve control of serum phosphate while taking into
account the effect of any calcium based binders used on serum calcium levels.
- It is recommended that total calcium load from calcium based phosphate binders should not exceed 1500mg per day (4,5)
- Consider the clinical circumstances of the patient: non-calcium based binders are often preferred in dialysis patients with
severe vascular and/or soft tissue calcifications (4, 5): if vascular calcification is noted in one part of the vascular tree (either
carotids, aorta, ileo-femoral or femoropopliteal) and calcium-phosphate product exceeds 4.4 mmol/l, imaging of the other
areas should be made. If positive in one other area, a non-calcium based binder should be considered (5).
- Routine assessments of vascular calcification in the form of plain xrays, ultrasound, coronary artery calcium scores, echo and/
or nuclear scans are carried out every 3 years for patients who are on the renal transplant list. Patients taking calcium binders
who have established cardiovascular disease (such as myocardial infarction), cerebrovascular disease (such as
cerebrovascular accident or transient ischaemic attack), peripheral vascular disease or diabetes should have more frequent
assessments at yearly intervals if considered clinically appropriate.
Monitoring:
Parameter Frequency (1) Target (1) Action
Serum 3-6 monthly Not on dialysis Dietary advice from Renal Dietitian. Adjustment of phosphate binder dosage and
phosphate for CKD4 0.9-1.5 mmol/l communication of changes between the Specialist, GP and Renal Dietitian.
1-3 monthly Dialysis
for CKD5 1.1-1.7 mmol/l
Serum 3-6 monthly Not on dialysis Adjustment of calcium /Vitamin D supplement dosage and communication of changes between
corrected for CKD4 2.1-2.6 mmol/l the Specialist, GP and Renal Dietitian. For haemodialysis patients, consider changing to lower
calcium 1-3 monthly Dialysis calcium dialysis fluid. Consider parathyroidectomy or calcimimetic agent (Cinacalcet) if calcium
for CKD5 2.2-2.5 mmol/l and PTH remain high (6).
Parathyroid 6-12 monthly Not on dialysis Adjustment of Vitamin D supplement dosage and communication of changes between the
Hormone for CKD4 normal lab range Specialist, GP and Renal Dietitian. Consider parathyroidectomy or calcimimetic agent
(PTH) 3-6 monthly Dialysis 2-9 x upper (Cinacalcet) if PTH and calcium remain high (6).
for CKD5 limit of normal

Supporting information:

Introduction: Phosphate retention occurs in chronic kidney disease due to the reduction in the glomerular filtration rate. Hypocalcaemia may also
develop due to the kidneys’ impaired ability to activate Vitamin D. High levels of phosphate and low levels of calcium stimulate secretion of parathyroid
hormone (PTH) from the parathyroid glands. PTH acts to restore the calcium/ phosphate balance by increasing calcium release from the bones into the
blood, reducing urinary calcium excretion and enhancing urinary phosphate excretion. In CKD4-5 this homeostasis becomes disrupted due to constant
parathyroid gland stimulation. This culminates in secondary hyperparathyroidism, hyperphosphataemia and hypercalcaemia, all of which play a
significant role in the development of renal bone disease, vascular calcification and its associated complications (e.g. cardiovascular disease,
cerebrovascular disease and peripheral vascular disease). This has a profound effect on both morbidity and mortality.
Dietary phosphate restriction can help to reduce phosphate and PTH levels. High phosphate foods include dairy foods, certain meat and fish, eggs,
chocolate, nuts, cola drinks and many processed foods. A reduced phosphate diet should be encouraged in patients who have high levels of phosphate
and/or PTH. The exception is for those patients who have a poor appetite, have a low body weight or have recently experienced significant unintentional
weight loss: restricting phosphate in these patients can compromise protein intake, which can in turn exacerbate the risk of malnutrition. Referral to a
Specialist Renal Dietitian is therefore recommended by NICE (2).
Oral phosphate binders are often required in addition to dietary phosphate restriction. Phosphate binders bind phosphate in the gut and reduce its
absorption. They must be taken with phosphate-containing foods to be effective. Ideally binders should be taken with all meals throughout the day. A
Renal Dietitian can advise on how best to distribute the binders: generally the larger the meal, the more phosphate binders are needed.
Alfacalcidol, an activated form of vitamin D, is often prescribed in patients with CKD4-5 as this helps to restore the phosphate/ calcium/ PTH balance.
Unfortunately, hypercalcaemia can often develop with increasing doses of alfacalcidol. If the PTH remains uncontrolled (greater than 85 pmol/l) and there
is a tendency for hypercalcaemia, a parathyroidectomy should be considered. If the risks of surgery outweigh the benefits, a calcimimetic agent (such as
Cinacalcet) can be used instead. This should be prescribed in accordance with NICE guidance (6).
Other measures that can be used to improve phosphate/ calcium/ PTH balance include using larger dialysers for haemodiaysis patients, changing to a
lower calcium haemodialysis fluid and maximising peritoneal dialysis regimens.

Who this pathway is for: This pathway is for healthcare professionals who look after adult patients with CKD stage 4 or 5, including those who are on
dialysis. This includes the primary and secondary care setting. Initiation and dosage change of phosphate binders, vitamin D supplementation and
calcimimetic agents will be directed by secondary care and communicated via letter to GPs.

Key changes to previous pathway (2009):


- Inclusion of latest NICE guidance (CG 157) and Evidence Update (72) regarding the use of calcium acetate first line
- Inclusion of more recently available phosphate binders, sucroferric oxyhydroxide and sevelamer carbonate
- Target levels and monitoring parameters now in line with Renal Association guidance
- Acknowledgement of the role of the medical and surgical management of secondary hyperparathyroidism

Audit measures:
- Serum phosphate, calcium and PTH levels of all haemodialysis patients to be analysed monthly and trends assessed
- Binder use to be audited in dialysis patients to establish compliance with the pathway

Produced by: Elizabeth Cartwright (Specialist Renal Dietitian, DGNFT), Dr Shivakumar (Renal Consultant Physician, DGNFT), Clair Huckerby
(Pharmaceutical Advisor, Dudley CCG). In consultation with: Jane Elvidge (Principle Pharmacist Medicines Management, DGNFT), Sarah Baig (Lead
Pharmacist Diabetes and Renal Medicine, DGNFT), Louise Crathorne (Lead Pharmacist General Medicine, DGNFT), Dr Rajendran (Renal Consultant,
DGNFT), Dr Samuel (Renal Consultant, DGNFT), Dr John (Renal Consultant, DGNFT)

References:
1. Renal Association. CKD-Mineral and Bone Disorders (CKD-MBD). Clinical Practice Guideline. March 2015.
2. NICE. Hyperphosphataemia in chronic kidney disease. Management of hyperphosphataemia in patients with stage 4 or 5 chronic kidney
disease. Clinical Guideline 157. March 2013.
3. NICE. Hyperphosphataemia in adults with chronic kidney disease on dialysis: sucroferric oxyhydroxide. Evidence Summary: New Medicine.
January 2015.
4. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for bone metabolism and disease in chronic kidney disease. October 2003.
5. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for cardiovascular disease in dialysis patients. April 2005.
6. NICE. Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis
therapy. NICE technology appraisal guidance 117. January 2007.

Bibliography:
1. Bover J et al. Intergral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate
imbalance to control of PTH and prevention of progression of cardiovascular calcification. Expert Opinion Pharmacotherapy Volume 13: 1-12
May 2016.
2. Chertow GM et al. Sevelamer attenuates the progression of coronary and aortic calcification in haemodialysis patients. Kidney International.
Volume 62: 245-252. July 2002.
3. Goodman WG et al. Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis. The New England
Journal of Medicine Volume 342: 1478-1483. May 2000.
4. Guerin AP et al. Arterial stiffening and vascular calcifications in end stage renal disease. Nephrology Dialysis Transplantation. Volume 15:
p1014-1021. July 2000.
5. NICE. Hyperphosphataemia in chronic kidney disease. Evidence Update (72). December 2014.
6. Wong ND et al. Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis
(MESA) JACC Cardiovascular Imaging. Volume 5: p358-366. April 2012.

Date updated: August 2016. Review date: August 2018