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Phosphate Control in Renal Disease
(instead of 1.75mmol/l).
Moreover, it has the advantage of allowing
Figure 1: Efficacy of Various Phosphate-binders at Clinically
the ingestion of larger doses of vitamin D, leading to better control of
Relevant pH In Vitro
renal bone disease. On the other hand, extended treatment with low-
calcium dialysate may be associated with an increased risk of severe
hyperparathyroidism unless serum calcium is carefully controlled.
Oral Phosphate-binding Agents
The search for an ideal phosphate-binder has been an important goal in the
management of renal bone disease since the discovery that kidney disease
impairs mineral metabolism. Traditionally, aluminium- or calcium-based
% phosphate binding
phosphate-binding agents have been used to treat hyperphosphataemia in
chronic renal failure and dialysis patients. Although these agents effectively
lower serum phosphate levels, they are associated with serious side effects.
Fortunately, several new agents are now available, including sevelamer
pH3 pH5 pH7
hydrochloride and lanthanum carbonate.
Many studies have demonstrated that both calcium carbonate and
calcium acetate are effective in treating hyperphosphataemia in dialysis compared with calcium carbonate in 32 stable haemodialysis patients
Hypercalcaemia is the most common problem (20–80%) (20 receiving calcium ketoglutarate and 12 receiving calcium
and is frequently severe enough to require withdrawal of the binder, carbonate). The incidence of hypercalcaemia (>2.8mmol/l) was
significantly higher in the carbonate group. Furthermore, a high
incidence of gastrointestinal complaints was reported in the
The main disadvantage of calcium ketoglutarate
The search for an ideal phosphate-
is its price compared with calcium acetate or carbonate. On the other
binder has been an important goal in the hand, it has a putative anabolic effect, which may improve malnutrition
management of renal bone disease since
in dialysis patients.
the discovery that kidney disease
Long-term adverse effects of calcium-containing phosphate-binders are
impairs mineral metabolism.
unknown. Tumoral calcinosis and calciphylaxis are serious concerns,
and these binders may increase the incidence of such problems. The
Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice
but gastrointestinal symptoms (such as change in bowel habit, vague Guidelines for Bone Metabolism and Disease in CKD recommended
abdominal discomfort and dyspepsia) are often reported. Calcium that the total dose of elemental calcium provided by calcium-based
carbonate does not bind phosphate optimally in all acid environments, phosphate-binders should not exceed 1,500mg/day, with total calcium
with the binding capacity reduced in the neutral pH range (around 7) intake per day from diet and binders to not exceed 2,000mg. The
as well as in the most acidic range (around 3). Conversely, calcium guidelines suggest that calcium-based binders should also be avoided in
acetate dissolves more easily at high gastric pH. Both acetate and dialysis patients who have a corrected plasma calcium level
carbonate are equivalent in their binding capacity, provided that
calcium carbonate is taken on an empty stomach a few minutes before
Although the daily intake of calcium is halved in patients who
take calcium acetate, the number of hypercalcaemic episodes is
comparable. Calcium acetate is capable of binding intestinal phosphate
Long-term adverse effects of
more effectively per mmol of administered elemental calcium than is calcium-containing phosphate-
calcium carbonate. Theoretically, 1g of the elemental calcium as the
binders are unknown.
carbonate would bind 43mg of phosphate, whereas 1g of calcium
acetate would bind 106mg.
Calcium alginate is a natural polyuronic acid that has been tested for its
capacity as a phosphate-binder in vivo and in vitro in haemodialysis and >2.55mmol/l or whose immunoreactive parathyroid hormone (iPTH
In 14 CAPD patients, calcium alginate did not cause level) is <150pg/ml (16.5pmol/l), or in patients with severe vascular
significant hypercalcaemia compared with calcium carbonate. One gram and/or soft-tissue calcifications, although this latter advice is opinion-
of calcium alginate contains only 102mg elemental calcium, whereas based only. Calcium citrate should be avoided in CKD, as citrate leads
calcium carbonate contains 400mg/g. However, patients achieved good to increased aluminium absorption.
phosphate control (1.6mmol/l) and did not require extra aluminium
supplements (placebo or control groups were not included).
Aluminium hydroxide dissolves rapidly and binds phosphate at any pH,
making it the most effective phosphate binder in vitro and in vivo. In
Calcium ketoglutarate is a semi-synthetic analogue of the amino acid patients taking aluminium hydroxide, plasma aluminium levels should
glutamic acid and exerts phosphate-binding properties. It was be measured monthly. Aluminium toxicity manifestations include
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