HYPERPARATHYROIDISM AND CALCIUM

Calcium metabolism is regulated by parathyroid hormone (PTH), calcitriol (1,25-dihydroxycholecalciferol), and calcitonin. The major organs involved in its regulation are the kidneys, the small intestine, and bone. The total calcium concentration is composed of three fractions: protein-bound calcium (35%), ionized calcium (50%), and complexed calcium (15%).¹⁰ Ionized calcium is the biologically active form.

Fewer than 10% of dogs with CKD have increased serum ionized calcium concentrations. When ionized calcium concentrations were measured in 490 dogs with CKD, 9% were hypercalcemic, 55% were normocalcemic, and 36% were hypocalcemic.¹² The use of adjustment formulas to correct total calcium based on serum protein or albumin concentrations are an inaccurate way to determine ionized calcium and are not recommended.¹³

In dogs and cats with secondary (renal) hyperparathyroidism, laboratory tests may reveal previous hypocalcemia or normocalcemia and hyperphosphatemia. In addition, dogs and cats with secondary hyperparathyroidism have extremely elevated intact PTH concentrations and decreased vitamin D concentrations. In contrast, dogs and cats with tertiary hyperparathyroidism, which occurs after a prolonged period of secondary hyperparathyroidism and excessive PTH stimulation, will have normal or elevated serum calcium concentrations in combination with moderately elevated intact PTH concentrations.¹⁰ Laboratory tests in patients with tertiary hyperparathyroidism may also reveal decreased vitamin D (1,25-dihydroxycholecalciferol, calcitriol) and phosphorus concentrations and elevated alkaline phosphatase activities.¹⁵

Hypercalcemia promotes soft tissue mineralization, which is most pronounced when the calcium-phosphorus product is > 50.¹⁶ Acute intrinsic renal failure occasionally develops as a consequence of hypercalcemia; however, chronic intrinsic renal failure is far more common.¹⁰ The main cause of hypercalcemia in dogs with potential subsequent hypercalcemic nephropathy is pseudohyperparathyroidism secondary to neoplasia, such as lymphoma, anal sac adenocarcinoma, mammary carcinoma, and multiple myeloma.^10,16 Azotemia caused by hypercalcemia may result from a combination of renal vasoconstriction, prerenal reduction in extracellular fluid volume (anorexia, hypodipsia, vomiting, and polyuria), and acute tubular necrosis from the ischemic and toxic effects of hypercalcemia. With CKD, nephrocalcinosis, tubulointerstitial inflammation, and interstitial fibrosis cause progressive nephron loss.

PHOSPHORUS

Phosphorus metabolism is regulated by the same hormones as calcium: PTH, calcitriol, and calcitonin. It is absorbed primarily in the duodenum, and absorption is increased by the influence of calcitriol. Intestinal phosphorus absorption is decreased with glucocorticoids, increased dietary magnesium, and hypothyroidism.

Phosphorus is primarily excreted by the kidneys. Most (80% to 90%) of the filtered load is reabsorbed by the proximal tubules. PTH decreases phosphorus reabsorption and is the most important regulator of renal phosphate transport.¹⁷

Hyperphosphatemia is commonly seen in patients with acute and chronic kidney disease because of decreased renal excretion. Other potential causes of hyperphosphatemia include increased intestinal absorption (vitamin D toxicosis, increased dietary phosphorus), from transcellular shifts (hemolysis, tumor lysis syndrome), or growth (juveniles, neonates).¹⁷ Hyperphosphatemia is not typically associated with clinical signs, but high concentrations leading to an elevated calcium x phosphorous product (> 50) may contribute to soft tissue mineralization.