Page 724 - Small Animal Internal Medicine, 6th Edition

696 PART V Urinary Tract Disorders

1,25-dihydroxycholecalciferol by 1α-hydroxylase. Total results in hyperphosphatemia, which in turn causes a recip-
serum calcium concentrations are decreased in approxi- rocal decrease in serum ionized calcium concentration by
VetBooks.ir mately 10% of dogs with CKD, but decreased serum ionized the mass law effect ([Ca] × [P i ] = constant). Ionized hypo-
calcemia stimulates the parathyroid glands to synthesize and
calcium concentration is found in 40% of dogs with CKD.
secrete PTH. The increase in PTH stimulates increased renal
Ionized hypocalcemia may occur in association with hyper-
phosphatemia in CKD as a consequence of the mass law excretion of phosphate and increased release of calcium and
effect. The amounts of calcium and phosphorus that can phosphate from bone, which returns the serum phosphorus
remain in solution together are defined by the [Ca] × [P i ] and ionized calcium concentrations to normal. PTH
product, where [Ca] is the serum calcium concentration and decreases the fractional reabsorption of phosphate in the
[P i ] is the serum phosphorus concentration. When this value kidney by decreasing the tubular maximum for phosphate
is more than 60 to 70, soft tissue mineralization occurs. In reabsorption. The limit of this compensatory response is
one study, the proportion of CKD dogs with [Ca] × [P i ] reached when the GFR declines to approximately 15% to
product >70 increased with increased stage of disease, and 20% of normal; when the GFR declines further, hyperphos-
mortality was higher (and survival time shorter) in dogs phatemia develops. Thus calcium and phosphorus balance is
with [Ca] × [P i ] product >70. Decreased production of cal- maintained by a progressive increase in the serum PTH con-
citriol by the diseased kidneys impairs intestinal absorption centration. A chronically increased PTH concentration leads
of calcium, and complexing of calcium with phosphate in the to bone demineralization and other toxic effects of uremia
lumen of the intestinal tract further impairs calcium absorp- (e.g., bone marrow suppression, uremic encephalopathy).
tion. Approximately 5% to 10% of dogs with CKD develop This sequence of events represents a trade-off for the main-
hypercalcemia, which may damage the kidney additionally tenance of calcium and phosphorus balance in progressive
by causing renal vasoconstriction and interstitial mineraliza- CKD.
tion. The serum ionized calcium concentration, however, The effect of phosphorus retention on renal calcitriol pro-
usually is normal or low when measured in dogs with CKD duction suggests an additional factor in the development of
that have increased total serum calcium concentrations. renal secondary hyperparathyroidism. Phosphorus retention
Hyperparathyroidism is a consistent finding progressive and hyperphosphatemia inhibit renal 1α-hydroxylase, which
CKD. Development of renal secondary hyperparathyroidism impairs the conversion of 25-hydroxycholecalciferol to
typically has been explained by the effect of phosphorus 1,25-dihydroxycholecalciferol (calcitriol). Impaired produc-
retention on serum ionized calcium concentration (Fig. 41.7, tion of calcitriol decreases the GI absorption of calcium,
A). Reduction in GFR decreases phosphate excretion and which in turn contributes to ionized hypocalcemia and

1000

120 800
GFR mL/min 105

PO 4 mg % 4.02 PTH 600
4.00
10.0 400
Ca mg % 9.98

60 200
PTH units 40

20 0
.2 .4 .6 .8 1.0 1.2 80 60 40 20 0
A Time (years) B GFR mL/min

FIG 41.7
(A) Classic theory of the development of renal secondary hyperparathyroidism according
to Slatopolsky (see text for explanation). (B) Effect of proportional restriction of dietary
phosphorus in progressive CKD on serum PTH concentration (open circles) as compared
with normal unrestricted dietary intake of phosphorus (closed circles). (From Slatopolsky E,
et al.: On the pathogenesis of hyperparathyroidism in chronic experimental renal
insufficiency in the dog, J Clin Invest 50:492, 1971.)