Page 215 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Phosphorus: Hypophosphatemia and Hyperphosphatemia 205

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decrease serum phosphorus concentration by promoting dialysis water. Aluminum can be absorbed from the
phosphorus entry into cells, although such therapy is intestinal tract in normal people 81 and uremic peo-
rarely, if ever, necessary. All sources of phosphorus intake ple, 14,34 and aluminum-induced bone disease can occur
should be curtailed. In the diet, phosphorus restriction is in nondialyzed patients after oral administration of alumi-
6
accomplished primarily by protein restriction. As a rule, num hydroxide. The toxicity of aluminum-containing
low-protein diets are also low in phosphorus. Calcium phosphate binders in human patients with renal failure
salts should not be administered to hyperphosphatemic is now well established, and they have been replaced by
patients because of the risk of metastatic soft tissue calci- calcium-containing phosphate binders. 50 It still is unclear
fication. Iatrogenic calcinosis cutis has been reported in whether aluminum-containing phosphate binders repre-
a dog and cat with hypoparathyroidism given calcium sent a hazard to dogs with chronic renal failure.
gluconate subcutaneously. 140,148 Calciumsalts suchascalcium carbonateand calcium ace-
In patients with severe, chronic renal failure, low-phos- tate also have been used as phosphate binders. Calcium car-
phorus diets are helpful but often insufficient. Dialysis is bonatedecreasesintestinalphosphate absorption innormal
*
unpredictable because phosphate is a poorly diffusible anduremicpeople. Calciumcitratealsohasbeenadvocated
ion. Therefore, the most practical and effective way to treat as a phosphate binder but should not be given with alumi-
hyperphosphatemiainpatientswithstablechronicrenalfail- num-containing compounds because citrate enhances alu-
ure is to decrease intestinal phosphate absorption by orally minum absorption. 40,64,113,122,156 Nausea, constipation,
administeredphosphatebinders.Suchadministrationhelps and hypercalcemia are potential side effects of calcium-
prevent ingested and endogenously secreted phosphate containing phosphate binders. Simultaneous use of
from being absorbed. Phosphate binders work because calcitriol and calcium-containing phosphate binders to
the cation in the binder combines with dietary phosphate, manage renal secondary hyperparathyroidism increases
producing insoluble, nonabsorbable phosphate theriskofhypercalcemia.Calciumacetatebindsmorephos-
compounds. Adsorption of phosphate ions on the surface phate than either calcium citrate or calcium carbonate, and
of binder particles may also contribute to their effect. The lesscalcium isabsorbed from theintestineduring its use. 152
rate atwhichabinderdissolvesdependsonitswatersolubil- Calciumacetatebindsphosphatebetter thanaluminumcar-
ity, the pH of the environment, and the dosage. 152 bonate at the neutral pH found in the small intestine, but
The most widely used oral phosphate-binding agents aluminum carbonate is better at the lower gastric pH. 152
contain aluminum or calcium and hydroxide, carbonate, In vivo, both were about equally effective.
or acetate (see Table 7-1). 35,75,160 The appropriate dos- Phosphate binders are most effective when given with
age must be determined empirically, but 90 to 100 meals. In one study, calcium acetate reduced intestinal
mg/kg/day divided two or three times daily is a reason- absorption of phosphate best when ingested just before
able starting point. Lower dosages of calcium acetate (50 or after a meal but was much less effective if given 2 hours
to 60 mg/kg/day) may be sufficient because it has a after eating. 150 Approximately one third as much phos-
greater capacity to bind phosphate than does calcium car- phate was removed from the body when calcium acetate
bonate. 105 Magnesium-containing compounds are not was given during fasting compared with when it was given
useful as phosphate binders because they cause diarrhea, with a meal. The endogenous phosphate removed prob-
and limited ability to excrete magnesium in renal failure ably originated from basal intestinal secretions or passive
42
patients increases the risk of hypermagnesemia . diffusion into the intestine. Ingestion of a meal also
Aluminumhydroxideandaluminumcarbonatearecom- decreased the absorption of calcium from the calcium ace-
monly used phosphate binders. Aluminum hydroxide tate. Thus, calcium-containing phosphate binders should
reduces intestinal phosphorus absorption in normal and be given with meals to reduce the risk of hypercalcemia.
uremic people. 34 Aluminum is a better binding agent for The search for new phosphorus binders has continued
phosphate than calcium or magnesium in the acidic gastric because of the bone toxicity and encephalopathy
152
environment. This effect is less important at the higher associated with use of aluminum-containing compounds
intestinal pH. Aluminum-containing gels are better and the hypercalcemia and soft tissue (including cardio-
tolerated by many dogs and cats when given as tablets or vascular) calcification associated with use of calcium-
capsules, but the desiccated form has a lower phosphate- containing compounds. 50 Sevelamer hydrochloride is a
binding capacity than the liquid gel. 142 Aluminum oxide cross-linked polymeric resin that binds phosphorus and
gelpreparedtomaximizephosphatebindinghasbeenstud- releases chloride. It does not contain aluminum or cal-
ied in dogs. 142,143 Constipation is a common side effect of cium. Sevelamer is believed to adhere to the mucosa of
aluminum-containing phosphate binders. the intestines, thus slowing its transit time and allowing
In people undergoing hemodialysis, osteomalacia and for extended periods of phosphate binding 58 It reduces
dialysis encephalopathy have been correlated with the alu- the risk of vascular and renal calcification that occurs in
minum content of dialysis water. 121 In one study, enceph-
alopathy occurred in dialysis patients receiving aluminum
hydroxide despite a negligible aluminum content of *References 7, 33, 61, 100, 106, 161