Page 154 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

144 ELECTROLYTE DISORDERS

hyperparathyroidism) contributes to the progression of reduced GFR caused by loss of renal mass could cause
renal disease. 402 Oral administration of low doses of increased iCa concentration as the filtered load of calcium
calcitriol reduces toxic concentrations of PTH, improves declines. Hyperplasia of the parathyroid gland chief cells
quality of life, reduces progression of renal disease, and could account for increased PTH secretion and serum cal-
leads to prolongation of life. 403,524 cium concentration because chief cells secrete small
Some cases of ionized hypercalcemia and CRF may be amounts of PTH that are nonsuppressible regardless of
associated with the use of calcium carbonate intestinal serum iCa concentration. 214
phosphate binders. In these cases, serum iCa concentra- Tertiary hyperparathyroidism refers to the condition
tion rapidly returns to normal after discontinuation of of a subset of patients with CRF who develop
treatment. In humans with CRF, therapeutic use of ionized hypercalcemia and excessive PTH secretion that
calcitriol is limited by development of hypercalcemia in is not inhibited by high serum iCa concentration. It is
patients also being treated with calcium-based dietary likely that such patients had high PTH concentrations
phosphorus binders. 126,403 In veterinary medicine, use in association with normal or low serum iCa concentra-
of aluminum-based phosphorus binders or sevelamer tion (renal secondary hyperparathyroidism) earlier in
largely precludes this problem. 10 “Noncalcemic the clinical course of CRF. Autonomous secretion of
analogues” of calcitriol have been developed for use in PTH from the parathyroid gland is unlikely, but
humans, 539 such as paricalcitol, 22-oxacalcitriol (OCT), the set-point for PTH secretion may be altered in CRF
and doxercalciferol. 155 These analogues have a very short such that higher concentrations of iCa are necessary to
half-life (several minutes), and this short half-life is inhibit PTH secretion. 215 Decreased serum calcitriol
responsible for their weak stimulation of intestinal cal- concentrations, decreased numbers of calcitriol receptors
cium absorption. Doses of noncalcemic analogues in the parathyroid gland, and decreased calcitriol-VDR
needed to suppress PTH synthesis are approximately interactions with chief cell DNA caused by uremic toxins
eightfold higher than that of calcitriol 539 and are up to may contribute to this increase in set-point, 75,266,435 as
12 times the cost. If hypercalcemia develops with may decreased levels of the calcium receptor, which both
calcitriol therapy, a twice-weekly dosing strategy of establish the set-point and depend on calcitriol function-
calcitriol is used. This dosing regimen will suppress ality for synthesis of its mRNA from the parathyroid cells’
PTH but be much less effective at stimulating intestinal DNA. 99 Ten dogs with CRF and increased serum tCa
calcium absorption. Noncalcemic analogues are not concentration were compared with those with normal
needed and are financially impractical in veterinary serum tCa concentration (Fig. 6-12). Serum amino-
medicine. terminal PTH concentration was markedly increased in
Ionized hypercalcemia occurs in patients with CRF both groups of uremic dogs, but those with increased
who receive excessive doses of calcitriol. Hypercalcemia tCa had higher PTH concentrations. Calcitriol concen-
is very uncommon in animals treated with the lower tration was decreased to a similar extent in both groups.
dosages of calcitriol (2.5 to 4.0 ng/kg daily). If hypercal- It was proposed that the hypercalcemic and more mark-
cemia is caused by excessive calcitriol, the serum tCa con- edly hyperparathyroid uremic dogs might have had
centration decreases during the week after its greater calcitriol receptor (VDR) deficits in their parathy-
discontinuation. Most CRF patients who develop an ele- roid cells, which would lead to poorly controlled PTH
vated tCa during low-dose calcitriol treatment have nor- synthesis and chief cell hyperplasia. 405 Deficient calcitriol
mal or low serum iCa concentrations. Serum tCa functionality caused by VDR deficits would also lead to
concentration may not decrease when calcitriol is calcium receptor deficits and the “set-point” elevations
discontinued if the increased serum tCa concentration involved in the observed hypercalcemia. 99
is caused by increased complexed calcium. Aluminum accumulation in the development of hyper-
The mechanisms of increased serum tCa concentration calcemia in dogs or cats with renal disease being treated
183,314,478,583
in CRF have not been well characterized. In with aluminum-containing intestinal phosphate binders
dogs with CRF, serum total hypercalcemia, and normal has not been investigated despite the fact that such treat-
iCa concentrations, the increase in serum tCa is caused ment is common. Experimental dogs exposed to alumi-
by an increase in the complexed calcium fraction. 517 In num developed mild hypercalcemia within minutes of a
CRF, organic anions such as citrates, phosphates, lactates, single intravenous injection. During chronic daily expo-
bicarbonates, and oxalates are capable of complexing with sure to aluminum during a period of weeks, serum cal-
calcium. Complexed calcium accounted for 24% of serum cium concentration progressively increased, and
tCa in those dogs with CRF and elevated serum tCa as azotemia developed. 242
compared with 11% in those dogs with CRF and low Two of 15 cats with CRF developed hypercalcemia
serum tCa. Increased PTH-mediated bone resorption while eating a phosphate-restricted veterinary diet
as a consequence of CRF could increase serum tCa con- designed for treatment of renal failure. Hypercalcemia
centration. If elevated iCa is also present, then the in these cats was associated with a decrease in serum