Benefits of calcitriol therapy and serum phosphorus control in dogs and cats with chronic renal failure. Both are essential to prevent of suppress toxic hyperparathyroidism.
Daily oral calcitriol at low doses is safe and effective in the control of renal secondary hyperparathyroidism in dogs and cats. Low doses of calcitriol are most effective when started early in uremia before the advanced stages of renal secondary hyperparathyroidism. At early stages calcitriol both diminishes PTH synthesis in the parathyroid cells present and prevents the hyperplasia that, if unchecked, results in the most extensive an difficult-to-control hyperparathyroidism. The salutary effects on the dog's or cat's sense of well being, appetite, activity, strength, and lifespan as reported by the veterinarians of our survey are attributed primarily to keeping PTH levels below a toxic threshold. Additionally, some of the benefits achieved by calcitriol are likely a direct consequence of calcitriol interacting with the vitamin D receptor in a wide variety of tissues throughout the body. Phosphorus restriction through a combination of diet and intestinal phosphate binders is important to allow calcitriol therapy to successfully lower PTH levels, but it likely has no direct effects that are independent of interactions involving calcitriol. Phosphorus restriction is also important to minimize chances for adverse tissue mineralization. Calcitriol therapy can be considered for treatment of chronic renal failure after serum phosphorus has been decreased to less than 6.0 mg/dL in patients in whom it was initially elevated. Calcitriol supplementation to dogs and cats with chronic renal failure makes good endocrinologic sense. Calcitriol deficits cause increased PTH and, as these two hormones are designed to maintain calcium and phosphorus homeostasis, the PTH increase is initially adaptive. One of the important effects of PTH is to stimulate additional calcitriol formation as a powerful means to raise blood calcium through increased calcium absorption from the diet. With too great an increase in PTH, however, its effects become harmful to many tissues due to the widespread distribution of the PTH receptor in many cell types that are likely normally responsive only to the paracrine PTH-related peptide that shares the PTH receptor. Exogenous supplemental calcitriol administration allows concentrations of calcitriol in the bloodstream to remain normal without the toxic consequences of excessive PTH secretion that would otherwise be provoked. Studies involving young dogs with subtotal nephrectomy may not parallel those on older dogs and cats with spontaneous chronic renal failure. In particular, higher doses are needed to effect PTH change in these young dogs than we have found necessary for older dogs and cats. Because survey participants agreed most strongly with the idea that their calcitriol-treated dogs and cats were living longer than comparably uremic animals they had treated previously, further studies to evaluate the ability of calcitriol to retard the progression of renal lesions and loss of excretory renal function seem warranted. Additional studies to document the beneficial effects of calcitriol on the many organs adversely affected by excess PTH during uremia are also needed because findings thoroughly documented and proven in humans and rats may not always extrapolate to dogs and cats.
Department of Veterinary Biosciences, Ohio State University, Columbus, USA.
L A
LA
Nagode
D J
DJ
Chew
M
M
Podell
D000818:Animals; D002117:Calcitriol / Q000627:therapeutic use*; D002371:Cat Diseases / Q000097:blood* / Q000188:drug therapy* / Q000517:prevention & control; D002415:Cats; D004283:Dog Diseases / Q000097:blood* / Q000188:drug therapy* / Q000517:prevention & control; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006980:Hyperthyroidism / Q000517:prevention & control / Q000662:veterinary; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood*; D016226:Phosphorus, Dietary / Q000592:standards; D014511:Uremia / Q000188:drug therapy / Q000662:veterinary
D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; D010758:Phosphorus; D002117:Calcitriol