EdRen - Edinburgh Royal Infirmary Renal Unit

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Calcium algorithm	Intractable problems
PTH, alfacalcidol and calcitriol	Calcium after parathyroidectomy
Aluminium	Further information
Phosphate algorithm	Patient information

Aims of management are maintenance of healthy skeletal architecture, through achieving normocalcaemia and limited hyperphosphataemia, and by controlling PTH. Monitoring frequencies etc are biased towards dialysis patients. Less often in pre-dialysis patients and transplant recipients.

Total calcium should be measured every 4-12 weeks and is often approximately corrected by adding 0.02mmol/l for every g/l the serum albumin is below 40g/l. This adjusted calcium can then be used, along with the iPTH taken every six months, to determine tratment according to the calcium algorithm below:

iPTH should be measured initially when GFR drops below 40-50mls/min. At this stage diet should be reviewed for both phosphate and protein content. High PTH levels should lead to introduction of alfacalcidol or calcitriol therapy, Calcium levels permitting. The standard starting dose is 0.25 micrograms (250 nanograms) daily. High iPTH results (eg > 500ng/l) may justify larger doses of calcitriol.

Note that the target range is higher than (2-4x) the normal range, in order to prevent adynamic bone disease resulting from overtreatment.

Alfacalcidol and Calcitriol are equally effective and equipotent. Both should be used at doses of 0.25, 0.5 or 1.0 micrograms for daily oral therapy. If the patient goes outwith the protocol limits, they should be taken out of the protocol and treated separately.

Aluminium should be measured every three months in patients on Al(OH)3. A result of greater than 2.2 micromol/l indicates a high risk of aluminium poisoning and requires cessation of Al (OH₃). Levels over 1 should lead to review of therapy.

Serum phosphate (Pi, PO₄) should be measured every 4-12 weeks to adjust therapy with phosphate binders. This can be done using the phosphate algorithm below:

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PHOSPHATE BINDERS

For inpatients, prescribe at 8, 12 and 6 and write "with food". Very approximately, one tablet of each is equivalent, except larger dose size for sevelamer.

Calcium acetate (CaAc) is the first-line binder for all patients unless they are hypercalcaemic. It is effective but delivers a significant calcium load. Hypercalcaemia may occur, and in the long term there is concern that excessive calcium load may accelerate vascular and extravascular calcification. Maximum dose is 6 tablets daily but this may be too much for long term therapy.

Calcium carbonate (CaCO₃) is a probably less effective alternative and contains more calcium, but may be useful if patients dislike the calcium acetate formulation.

Aluminium hydroxide (e.g. Alucaps) is an effective binder that is relatively palatable. However it is generally considered less suitable for long-term use because of concerns about aluminium accumulation and toxicity in renal failure. Monitor Al levels during therapy and be cautious about duration.

Sevelamer (Renagel) is an expensive binder that does not cause calcium loading or other known serious long-term toxicity. Used alone it is probably less effective at lowering phosphate and its track record is still relatively short. It is indicated when:

High serum phosphate levels in conjunction with serum corrected calcium above 2.6mmol/l
Calcium-containing binders unable to achieve adequate control without high calcium dose (=/>6 tablets/day) or hypercalcaemia
Aluminium hydroxide therapy has been required for more than 3 months

Lanthanum carbonate (Fosrenol) is an expensive calcium-free second line phosphate binder: fewer tabs than sevelamer but some GI side effects.

Other agents are in development. See also 'intractable problems' below.

Phosphate binder type/ dose is decided using measurements of corrected calcium and phosphate (and see above):

Ca >2.6: follow the algorithm above for management of alfacalcidol/calcitriol therapy, and consider changing the alfacalcidol or calcitriol dose. Otherwise/also:

If on CaAcetate, consider change to Al(OH)₃
If on non-calcium binders, discuss - review PTH level, other cause
If intractable and on dialysis, consider lowering dialysate calcium

Ca 2.16 - 2.6

If on Al(OH)₃ change (back) to Ca Acetate (if other factors corrected).

Ca <2.16: follow algorithm above for management of alfacalcidol/ calcitriol therapy. Otherwise/also:

If already on Ca Acetate and PO₄ over 1.5, increase CaAc dose
If Pi below 1.5, give CaAc between meals as a supplement

Intractable problems with calcium and phosphate

Compliance is always an important question
Phosphate clearance on dialysis is mainly determined by duration - supplementation may be required with continuous treatments or on daily dialysis
Parathyroidectomy is usually required at some point in the lifetime of patients who have spent many years on dialysis
Cinacalcet activates calcium-sensing receptors, leading to reduction of PTH secretion and falls in serum Ca and PO₄ through reduced mobilisation from bone. It seems very effective, but is expensive, track record is still relatively short, given the context in which it is used, and its place in long-term therapy has yet to be established.

Parathyroidectomy: management of calcium

Patients with substantial hyperparathyroidism may develop severe hypocalcaemia immediately after parathyroidectomy ("hungry bones"). This is most likely if bone disease is obvious and severe, and may be minimised by pre-administration of alfacalcidol or calcitriol.

Preop - prescribe alfacalcidol or calcitriol 2-4 micrograms dailys for 3-5 days pre-op, and continued postoperatively until [Ca] is normal. This is safe for 3 days even if [Ca] is high preoperatively.
Continue usual phosphate binders but stop Cinacalcet
Make sure you check Ca and PO4 pre-op
Postop - Measure [Ca] after return from theatre and at 4-8h intervals according to the level and the rate of change. If normal at 48h, further trouble is very unlikely.
Continue alfacalcidol but keep doubling dose (to max 8-10 micrograms/day) if substantial calcium supplements required.
If calcium falls below normal (but <1.9) or rapidly, give oral calcium supplements unless symptomatic. Sandocal 1000, 2 tds is a reasonable starting dose. More on calcium supplementation
If Ca <1.9mmol/l, or if symptomatic, treat with IV calcium: More on calcium supplementation.
Check [Mg] intermittently if [Ca] is causing trouble
After discharge - [Ca] should be checked 2-3x/week until stable. (Before dialysis if on HD). Increase alfacalcidol/calcitriol if low or continuing to require calcium supplementation.